Clinical Manual of

Psychosomatic Medicine
A Guide to Consultation-Liaison Psychiatry

Second Edition
This page intentionally left blank
 Clinical Manual of
Psychosomatic Medicine
A Guide to Consultation-Liaison Psychiatry

Second Edition

by

Kemuel L. Philbrick, M.D.

Assistant Professor of Psychiatry, College of Medicine at Mayo Clinic,
Rochester, Minnesota

James R. Rundell, M.D.

Professor of Psychiatry, College of Medicine at Mayo Clinic,
and Consultant in Psychiatry at Mayo Clinic, Jacksonville, Florida

Pamela J. Netzel, M.D.

Assistant Professor of Psychiatry, College of Medicine at Mayo Clinic,
Rochester, Minnesota

James L. Levenson, M.D.

Professor of Psychiatry, Medicine, and Surgery,
Virginia Commonwealth University School of Medicine, Richmond, Virginia

Washington, DC
London, England
Note: The authors have worked to ensure that all information in this book is accurate at
the time of publication and consistent with general psychiatric and medical standards, and
that information concerning drug dosages, schedules, and routes of administration is
accurate at the time of publication and consistent with standards set by the U.S. Food and
Drug Administration and the general medical community. As medical research and practice
continue to advance, however, therapeutic standards may change. Moreover, specific
situations may require a specific therapeutic response not included in this book. For these
reasons and because human and mechanical errors sometimes occur, we recommend that
readers follow the advice of physicians directly involved in their care or the care of a member
of their family.
Books published by American Psychiatric Publishing (APP) represent the findings,
conclusions, and views of the individual authors and do not necessarily represent the policies
and opinions of APP or the American Psychiatric Association.
Copyright © 2012 American Psychiatric Association
ALL RIGHTS RESERVED
Manufactured in the United States of America on acid-free paper
15 14 13 12 11 5 4 3 2 1
First Edition
Typeset in AGaramond and Fomata Regular.
American Psychiatric Publishing, a Division of American Psychiatric Association
1000 Wilson Boulevard
Arlington, VA 22209-3901
www.appi.org
Library of Congress Cataloging-in-Publication Data
Clinical manual of psychosomatic medicine : a guide to consultation-liaison psychiatry / by
Kemuel L. Philbrick ... [et al.]. — 2nd ed.
p. ; cm.
Rev. ed. of: Clinical manual of psychosomatic medicine / Michael G. Wise, James R.
Rundell. 1st ed. c2005.
Includes bibliographical references and index.
ISBN 978-1-58562-393-8 (pbk. : alk. paper) 1. Consultation-liaison psychiatry. 2.
Medicine, Psychosomatic. I. Philbrick, Kemuel L., 1956– II. Wise, Michael G., 1944–
Clinical manual of psychosomatic medicine.
[DNLM: 1. Psychophysiologic Disorders—diagnosis. 2. Psychophysiologic Disorders—
therapy. 3. Mental Disorders—diagnosis. 4. Mental Disorders—therapy. 5. Psychotherapy—
methods. 6. Referral and Consultation. WM 90]
RC455.2.C65W568 2012
616.89¢14—dc23
2011026355
British Library Cataloguing in Publication Data
A CIP record is available from the British Library.
 Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xix

PART I
General Considerations

1 Effective Psychiatric Consultation . . . . . . . . . . . . . 3

History of Psychiatric Consultation . . . . . . . . . . . . . . 3
Trends Affecting Psychosomatic Medicine Practice . 4
Business of Consultation Practice . . . . . . . . . . . . . . . 5
Characteristics of Effective Psychiatric Consultants . 7
Approach to Consultation. . . . . . . . . . . . . . . . . . . . . . 8
Outpatient Psychosomatic Medicine
Consultation Models . . . . . . . . . . . . . . . . . . . . . . . . . 10
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

2 Medicolegal Issues . . . . . . . . . . . . . . . . . . . . . . . . . 13
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Patient Confidentiality. . . . . . . . . . . . . . . . . . . . . . . . 14
Informed Consent and Right to
Direct Medical Treatment . . . . . . . . . . . . . . . . . . . . . 16
Capacity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Guardianship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Involuntary Hospitalization. . . . . . . . . . . . . . . . . . . . 24
Seclusion and Restraint . . . . . . . . . . . . . . . . . . . . . . 25
Prescribing Medications for Nonapproved Uses . . 26
Malpractice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3 Mental Status and Cognitive Examination . . . . . . 31
Noncognitive Elements of Mental Status
Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Cognitive Elements of Mental Status
Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Screening Tools for Bedside Cognitive
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Other Useful Tests of Cognitive Function . . . . . . . . 41
Tests of Executive Function . . . . . . . . . . . . . . . . . . . 44
Neurological Examination. . . . . . . . . . . . . . . . . . . . . 46
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

4 Personality and Response to Illness . . . . . . . . . . . 51

The Person . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Personality Patterns of Patients . . . . . . . . . . . . . . . . 54
Common Defenses in Medical Patients . . . . . . . . . 64
Helping the Patient Cope Constructively . . . . . . . . 65
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

5 Suicidality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Clinical Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . 71
Treatment and Management . . . . . . . . . . . . . . . . . . 72
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

PART II
Syndromes
6 Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Biology of Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Anxiety Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 85
 Treatment and Management . . . . . . . . . . . . . . . . . . 86
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

7 Delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Recognition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Consultation Effectiveness . . . . . . . . . . . . . . . . . . . . 97
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Predisposing Factors . . . . . . . . . . . . . . . . . . . . . . . . . 99
Precipitating Factors and Etiologies. . . . . . . . . . . . 100
Clinical Characteristics . . . . . . . . . . . . . . . . . . . . . . 103
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Management and Symptomatic Treatment . . . . . 110
Morbidity and Mortality Risks Associated
With Antipsychotic Medications . . . . . . . . . . . . . . . 114
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
8 Dementia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Clinical Features of Dementia . . . . . . . . . . . . . . . . 120
Risk Factors for Dementia. . . . . . . . . . . . . . . . . . . . 121
Major Types of Dementia . . . . . . . . . . . . . . . . . . . . 122
Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
9 Eating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Definitions and Clinical Features . . . . . . . . . . . . . . 145
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
Assessment and Differential Diagnosis . . . . . . . . . 148
Medical Complications . . . . . . . . . . . . . . . . . . . . . . 149
Concurrent General Medical Conditions . . . . . . . . 152
Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
10 Mood Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
Bipolar Disorder and Secondary Mania. . . . . . . . . 178
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

11 Sleep Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

Sleep Stages in Healthy Adults . . . . . . . . . . . . . . . 195
Sleep-Related Difficulties Associated
With Medical Problems. . . . . . . . . . . . . . . . . . . . . . 196
Evaluation of Sleep . . . . . . . . . . . . . . . . . . . . . . . . . 196
Insomnia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Sleep-Related Breathing Disorders . . . . . . . . . . . . 202
Hypersomnias of Central Origin. . . . . . . . . . . . . . . 203
Circadian Rhythm Sleep Disorders . . . . . . . . . . . . 203
Parasomnias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
Sleep-Related Movement Disorders . . . . . . . . . . . 205
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

12 Somatoform and Related Disorders . . . . . . . . . . 209

A Challenging Arena . . . . . . . . . . . . . . . . . . . . . . . . 210
General Principles of Approach . . . . . . . . . . . . . . . 215
Somatization Disorder . . . . . . . . . . . . . . . . . . . . . . 221
Undifferentiated Somatoform Disorder. . . . . . . . . 222
Hypochondriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
Conversion Disorder . . . . . . . . . . . . . . . . . . . . . . . . 226
Body Dysmorphic Disorder. . . . . . . . . . . . . . . . . . . 230
Pain Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
Factitious Disorders. . . . . . . . . . . . . . . . . . . . . . . . . 235
Malingering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
13 Substance-Related Disorders . . . . . . . . . . . . . . . . 245
DSM Criteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Sedatives, Hypnotics, and Anxiolytics . . . . . . . . . . 257
Opiates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Amphetamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Cocaine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267

PART III
Treatments
14 Biological Treatments . . . . . . . . . . . . . . . . . . . . . . 273
Adherence to Pharmacological Treatment . . . . . . 273
Pharmacokinetics in Medically Ill Patients . . . . . . 274
Drug Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Serotonin Syndrome . . . . . . . . . . . . . . . . . . . . . . . . 282
Neuroleptic Malignant Syndrome . . . . . . . . . . . . . 285
Psychotropic Use and Cardiac Complications . . . 289
Psychotropic Use and Endocrine-Related
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Psychotropic Use in Renal Disease . . . . . . . . . . . . 292
Psychotropic Use in Liver Disease . . . . . . . . . . . . . 293
Nonpharmacological Treatments. . . . . . . . . . . . . . 294
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296
15 Psychosocial Management . . . . . . . . . . . . . . . . . . 301
Culture, Ethnicity, and Language . . . . . . . . . . . . . . 301
Spiritual, Existential, and Religious Factors . . . . . . 305
Patient’s Practical Concerns . . . . . . . . . . . . . . . . . . 306
Promoting Resilience Rather Than Vulnerability . 308
Additional Supportive Tools . . . . . . . . . . . . . . . . . . 308
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
 PART IV
Unique Issues in
Psychosomatic Medicine Settings

16 Bariatric Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . 319

Types of Bariatric Surgery . . . . . . . . . . . . . . . . . . . . 319
Criteria for Bariatric Surgery . . . . . . . . . . . . . . . . . . 320
Medical Assessment of the Potential
Bariatric Surgery Patient . . . . . . . . . . . . . . . . . . . . . 320
Psychiatric Assessment of the Potential
Bariatric Surgery Patient . . . . . . . . . . . . . . . . . . . . . 321
Presurgical Psychiatric Management . . . . . . . . . . . 325
Perioperative Psychiatric Management . . . . . . . . . 326
Postoperative Psychiatric Management . . . . . . . . 326
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327

17 Cardiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Relationship Between Depression
and Cardiovascular Disease . . . . . . . . . . . . . . . . . . 329
Comorbidity Mechanisms. . . . . . . . . . . . . . . . . . . . 331
Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
Special Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Treatment Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335

18 Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
Delusional Psychocutaneous Conditions . . . . . . . 339
Somatoform Psychocutaneous Conditions. . . . . . 341
Factitious Psychocutaneous Conditions . . . . . . . . 342
Psychiatric Disorders With Dermatological
Consequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
Dermatological Conditions Exacerbated
by Psychological Factors . . . . . . . . . . . . . . . . . . . . . 345
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
19 Disaster and Terrorism Casualties . . . . . . . . . . . . 349
Unique Considerations in Clinical Evaluation. . . . 350
Unique Considerations in Diagnosis
and Management . . . . . . . . . . . . . . . . . . . . . . . . . . 351
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357

20 Endocrinology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Thyroid Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
Parathyroid Disorders . . . . . . . . . . . . . . . . . . . . . . . 365
Adrenal Gland Disorders. . . . . . . . . . . . . . . . . . . . . 366
Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Pheochromocytoma . . . . . . . . . . . . . . . . . . . . . . . . 367
Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Other Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369

21 Fatigue and Fibromyalgia . . . . . . . . . . . . . . . . . . . 373

Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Fibromyalgia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382

22 Gastroenterology . . . . . . . . . . . . . . . . . . . . . . . . . . 385
Oropharyngeal and Upper Gastrointestinal
Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
Irritable Bowel Syndrome. . . . . . . . . . . . . . . . . . . . 388
Inflammatory Bowel Disease . . . . . . . . . . . . . . . . . 389
Hepatitis C Virus . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
Other Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 394

23 HIV and AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399

Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Psychiatric Manifestations . . . . . . . . . . . . . . . . . . . 401
 Psychiatric Treatment . . . . . . . . . . . . . . . . . . . . . . . 405
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408

24 Obstetrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
Maternal Depression, Adverse Reproductive
Outcomes, and Comorbid Medical Problems . . . 413
Screening for Depression . . . . . . . . . . . . . . . . . . . . 414
Treatment of Depression and Anxiety
During Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . 414
Treatment of Postpartum Depression . . . . . . . . . . 419
Breast-Feeding and Drugs . . . . . . . . . . . . . . . . . . . 419
Treatment of Bipolar Disorder During
Pregnancy and the Postpartum Period . . . . . . . . . 420
Use of Antipsychotics During Pregnancy
and the Postpartum Period . . . . . . . . . . . . . . . . . . 421
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422

25 Oncology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Depression and Anxiety . . . . . . . . . . . . . . . . . . . . . 427
Mania . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Pain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
Cancer-Related Fatigue. . . . . . . . . . . . . . . . . . . . . . 433
Delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Cancer-Related Anorexia-Cachexia Syndrome . . . 435
Treatment of Hot Flashes . . . . . . . . . . . . . . . . . . . . 435
End-of-Life Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437

26 Pulmonary Disease . . . . . . . . . . . . . . . . . . . . . . . . 441

Common Pulmonary Conditions . . . . . . . . . . . . . . 441
Psychiatric Symptoms Associated With
Pulmonary Medications . . . . . . . . . . . . . . . . . . . . . 448
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
27 Rehabilitation Medicine . . . . . . . . . . . . . . . . . . . . 451
Traumatic Brain Injury. . . . . . . . . . . . . . . . . . . . . . . 451
Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
Spinal Cord Injury . . . . . . . . . . . . . . . . . . . . . . . . . . 460
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 462

28 Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . 467
General Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467
Pretransplantation Issues . . . . . . . . . . . . . . . . . . . . 468
Perioperative and Postsurgical
Recovery Period Issues . . . . . . . . . . . . . . . . . . . . . . 471
Posttransplantation Issues . . . . . . . . . . . . . . . . . . . 473
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
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 List of Tables and Figures
Table 6–1 Benzodiazepines in medical-surgical patients . . . . . . . 88

Figure 7–1 Relationship between vulnerability and

etiology in delirium . . . . . . . . . . . . . . . . . . . . . . . . . . .100
Table 7–1 Common medications associated with delirium . . . .101
Table 7–2 Frequency of symptoms in an elderly medical
inpatient population diagnosed with delirium . . . . . .103
Table 7–3 The 3 Ds: delirium, dementia, and depression . . . . .108
Table 7–4 Antipsychotic medication management of
delirium symptoms: average daily dosages . . . . . . . .112
Table 7–5 Haloperidol management of hyperactive delirium:
starting doses and administration guidelines . . . . . . .113

Table 8–1 DSM-IV-TR diagnostic criteria for dementia of

the Alzheimer’s type . . . . . . . . . . . . . . . . . . . . . . . . . .124
Table 8–2 DSM-IV-TR diagnostic criteria for vascular
dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .126
Table 8–3 Diagnostic criteria for dementia with Lewy bodies . .128
Table 8–4 American Neuropsychiatric Association
consensus criteria for frontotemporal dementia . . . .130
Table 8–5 Differential diagnosis of dementias and
subacute confusional states . . . . . . . . . . . . . . . . . . . .132
Figure 8–1 A hierarchical approach to diagnosing
mild cognitive impairment, dementia, and
the major subtypes of dementia. . . . . . . . . . . . . . . . .133
Table 8–6 Assessment of daily activities . . . . . . . . . . . . . . . . . . .134
Table 8–7 Diagnostic evaluation for dementia . . . . . . . . . . . . . .136

Table 9–1 Medical differential diagnosis of eating disorders . . .150

Table 9–2 Eating disorder symptoms and medical effects . . . . .151
Table 10–1 DSM-IV-TR diagnostic criteria for major
depressive episode . . . . . . . . . . . . . . . . . . . . . . . . . . .164
Table 10–2 Medical conditions and toxic agents associated
with secondary depressive disorders . . . . . . . . . . . . .166
Table 10–3 Differentiating depression and dementia . . . . . . . . . .168
Table 10–4 Clinical situations in which psychostimulants
are an important treatment option . . . . . . . . . . . . . . .174
Table 10–5 Selected causes of secondary mania . . . . . . . . . . . . .181

Table 11–1 Selected causes of insomnia. . . . . . . . . . . . . . . . . . . .199

Table 11–2 Strategies for sleep hygiene . . . . . . . . . . . . . . . . . . . .199
Table 11–3 Medications for treatment of insomnia. . . . . . . . . . . .201

Table 14–1 Medication principles in the psychosomatic

medicine setting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .275
Table 14–2 Cytochrome P450 (CYP)–drug interactions. . . . . . . .278
Table 14–3 Drugs associated with serotonin syndrome . . . . . . . .282
Figure 14–1 Serotonin syndrome: spectrum of clinical
findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .283
Table 14–4 Characteristics of serotonin syndrome
and related clinical conditions . . . . . . . . . . . . . . . . . . .286

Table 15–1 Existential postures: themes of resilience

versus vulnerability. . . . . . . . . . . . . . . . . . . . . . . . . . . .310

Table 19–1 Screening psychiatric examination of

medical-surgical disaster casualties. . . . . . . . . . . . . . .352
Table 19–2 Studies demonstrating efficacy of selective
serotonin reuptake inhibitors (SSRIs) in
posttraumatic stress disorder. . . . . . . . . . . . . . . . . . . .355

Table 21–1 Differential diagnosis for chronic fatigue. . . . . . . . . . .375

Table 21–2 Consensus criteria for chronic fatigue syndrome . . . .377
Table 24–1 Guidelines for medication use during pregnancy
or breast-feeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . .416

Table 25–1 Medical causes of anxiety in cancer patients . . . . . . .432

Table 25–2 Causes of cancer-related fatigue . . . . . . . . . . . . . . . .434
Table 25–3 Neuropsychiatric side effects of common
chemotherapeutic agents . . . . . . . . . . . . . . . . . . . . . .436
This page intentionally left blank
Preface

“Doctors learn at two levels: 1) the scientific, when the variables can
be properly controlled, and 2) experiential, frequently without un-
derstanding, when the variables are uncontrolled.” So wrote Eugene
Stead, M.D., longtime Chair (1947–1967) of the Department of
Medicine at Duke University. Although an internist, he also mused,
“Many nervous systems are capable of doing things that you think
your nervous system wouldn’t think possible.” Capturing the inter-
section of art and science, Dr. Stead summarized, “All disease sits in
the substrate of a person: the soil in which things grow.”
(Wagner et al. 1981, pp. 14, 16, 77)

The physician who finds the collision—or collusion—of medical, surgical,

and psychiatric difficulties fascinating, fun, and challenging will find a friend
in this volume. Internists, family physicians, psychiatry residents, and psychi-
atric consultants alike commonly encounter patients in whom the interface of
medicine and psychiatry complicate disease and suffering. The authors intend
the 28 chapters of this book to provide rich but practical and concise resources
for the busy clinician in four sections:

1. General Considerations, such as medicolegal issues, mental status, person-

ality, and suicidal issues in the medically ill;
2. Syndromes that occur frequently, such as anxiety, delirium, mood disor-
ders, somatoform disorders, and substance abuse problems;
3. Treatments, including biological and psychopharmacological as well as
psychosocial strategies; and

xix
xx Clinical Manual of Psychosomatic Medicine

4. Unique Issues in Psychosomatic Settings, which include 13 areas such as car-

diology, disaster and terrorism, fatigue and fibromyalgia, gastroenterol-
ogy, oncology, and transplantation.

We believe it is essential for the informed physician who has trained as a

psychiatrist to maintain 1) expertise in the administration and interpretation
of the mental status examination, 2) knowledge about medical conditions and
treatments, 3) expertise in identifying toxic and medical causes of psychiatric
signs and symptoms, 4) skill in both psychopharmacology and psychotherapy,
5) dexterity in forming comprehensive biopsychosocial differential diagnoses,
and 6) the ability to work comfortably and communicate clearly with medi-
cal-surgical colleagues.
We dedicate this second edition of the Clinical Manual of Psychosomatic
Medicine to Michael G. Wise, M.D. In 1987, Dr. Wise coauthored the first
edition of the Concise Guide to Consultation Psychiatry. He also coauthored the
second and third editions of that text, published in 1994 and 2000, respec-
tively. The Concise Guide was the predecessor to the first edition of the Clin-
ical Manual of Psychosomatic Medicine, published in 2005, a work also coau-
thored by Dr. Wise. He further coauthored the first comprehensive textbook
of Psychosomatic Medicine, The American Psychiatric Publishing Textbook of
Consultation-Liaison Psychiatry, the first edition of which was published in
1996 and the second edition in 2002. These important textbooks blazed the
trail for the current flagship textbook of our subspecialty, The American Psy-
chiatric Publishing Textbook of Psychosomatic Medicine, and were accompanied
by study guides and condensed versions. Dr. Wise, through his ground-break-
ing writing and through his loving mentorship of literally hundreds of general
psychiatrists and psychosomatic medicine psychiatrists, has made an endur-
ing impact on our subspecialty. In fact, he trained and mentored two of the
authors of this book. For all of his contributions to our field, we owe Michael
Wise an enormous debt of gratitude, and we are honored to dedicate this
work to him.
Special thanks are due John McDuffie and Rebecca Richters of American
Psychiatric Publishing (APP). Mr. McDuffie, Editorial Director at APP, or-
chestrated the conception and development of the project. Once a manuscript
emerged, Ms. Richters, Senior Editor, Books, at APP choreographed the trans-
formation of 500 pages of raw text into the book you are now reading. The fin-
 Preface xxi

ished product would simply never have seen the light of day but for their
patient perspicacity and good humor.

Kemuel L Philbrick, M.D.

James R. Rundell, M.D.
Pamela J. Netzel, M.D.
James L. Levenson, M.D.

Reference
Wagner GS, Cebe B, Rozear MP, eds: To care for the person who has the illness, and,
Most medical problems are not curable, in E. A. Stead, Jr.: What this patient
needs is a doctor. Edited by Wagner GS, Cebe B, Rozear MP. Durham, NC, Duke
Hospital, 1981, pp 14, 16, 77

Disclosure of Competing Interests

The authors had no competing interests during the year preceding manuscript sub-
mission.
This page intentionally left blank
 PA R T I

General Considerations
This page intentionally left blank
 1
Effective Psychiatric Consultation

History of Psychiatric Consultation

1920s–1930s
Psychosomatic medicine (PM) and consultation-liaison (CL) psychiatry be-
gan in the 1920s and 1930s with the development of general hospital psychi-
atry units and the PM movement (Lipowski and Wise 2002).

1930s–1950s
Rockefeller Foundation grants in 1934 and 1935 aided development of con-
sultation psychiatry by establishing closer collaboration between psychiatrists
and other physicians. A number of psychoanalysts contributed specific psy-
chosomatic theories to the field during the 1930s through 1950s.

1960s–1970s
During the 1960s and 1970s, the number of CL psychiatry services grew, and
a subspecialty scientific literature developed. In 1974, under the leadership of
James Eaton, the Psychiatry Education Branch of the National Institute of

3
4 Clinical Manual of Psychosomatic Medicine

Mental Health (NIMH) supported the development and expansion of CL

services throughout the United States, in part by providing grants for CL fel-
lowships (Eaton et al. 1977). By 1980, NIMH supported 130 programs and
materially contributed to the training of more than 300 CL psychiatry fellows
(Lipowski and Wise 2002).

1980s–1990s
Federal budget cuts in the 1980s dramatically decreased the number of sti-
pends for the “Eaton fellowships.” Nevertheless, CL psychiatry continued to
grow and develop during the 1980s and 1990s (Lipowski and Wise 2002), es-
pecially in academic and larger medical centers.

Since 2000
In 2003, the American Board of Medical Specialties (ABMS) approved PM as a
subspecialty, and the American Board of Psychiatry and Neurology (ABPN) es-
tablished a certifying examination. These actions have resulted in an expansion
of PM fellowships and a move toward standardization of training requirements
by the Accreditation Council for Graduate Medical Education (ACGME). The
scope of the subspecialty, as defined by a list of competencies developed by the
Academy of Psychosomatic Medicine (APM), the American Psychiatric Asso-
ciation (APA), and the ABPN, has become firmly established in both outpa-
tient and inpatient consultative settings (Rundell et al. 2008; Worley et al.
2009). The emphasis on multidisciplinary, integrated care delivery is increasing
in both primary care and specialty care settings (Kathol et al. 2009).

Trends Affecting Psychosomatic Medicine Practice

Limited Reimbursements
Direct reimbursement for psychiatric consultations, especially inpatient consul-
tations, is limited. Medicare recently abolished consultation billing codes. PM
psychiatrists must educate institutional physician and administration leaders
about the value of consultation psychiatry in cost offset and quality of care out-
comes. Payers often “carve out” psychiatric and other mental health payment
structures from medical and surgical ones, increasing the difficulty of receiving
reimbursements for psychiatric services to medical-surgical patients.
 Effective Psychiatric Consultation 5

Outpatient Consultation
The scope of practice of PM in the outpatient setting is distinct from that of
general outpatient psychiatry (Rundell et al. 2008). The most frequent condi-
tions seen in the outpatient PM setting are depression and/or anxiety in pa-
tients who are medically ill, and unexplained medical symptoms. The enriched
case mix, when added to the most frequent cases seen in inpatient CL work (de-
lirium, depression, capacity determination, dementia), is an asset for fellowship
and residency training.

Integrated Care
Psychiatric care provided in settings other than mental health sites has always
been part of PM practice. Concepts of liaison psychiatry have evolved to the
current models of integrated care. Integrated care involves the provision, by
multidisciplinary team members, of individualized but evidence-based care
based on either a clinical condition (e.g., obesity, infertility) or treatment set-
ting (e.g., primary care, transplantation) (Kathol et al. 2009). Data support
the efficacy of integrated care in terms of clinical outcomes, financial perfor-
mance, and patient and provider satisfaction (Hunkeler et al. 2006; Kathol et
al. 2009).

Subspecialty Certification
Since 2003, PM has been a recognized subspecialty of the ABMS. Although
this status has not necessarily translated into improved financial viability of
PM or CL services, it has resulted in standardization across training programs
and academic departments. Consensus core competencies that define the sub-
specialty have been adopted and serve as benchmarks for skill development
and affirmation (Worley et al. 2009).

Business of Consultation Practice

Make the Case to Payors That Psychiatric Disorders Are
Frequent and Add to the Cost of Health Care

• Psychiatric disorders are frequent. From 30% to 60% of general hospital in-
patients have diagnosable psychiatric disorders (Hall et al. 2002).
6 Clinical Manual of Psychosomatic Medicine

• Psychiatric disorders increase health care costs. Depression, anxiety, and cogni-
tive dysfunction each has been shown to predict longer hospital stays and
greater hospitalization costs, even after accounting for demographics, degree
of physical impairment, type of hospital unit, medical diagnosis, and cir-
cumstances of admission (Levenson et al. 1990; Saravay and Lavin 1994).
• Comorbidity increases health care costs. Medical-psychiatric comorbidity
predicts poorer outcomes and increased health care use and cost (Druss
and Rosenheck 1999).
• Psychiatric consultation is cost-effective. Psychiatric consultation for general
hospital patients and medical-surgical outpatients may reduce mortality,
morbidity, length of stay, and hospital costs (Hall et al. 2002).

Make the Case That Maintaining the Financial Viability of

Psychosomatic Medicine Services Is Essential to
Overall Institutional Financial Performance
Psychiatric consultation services need to make the case that maintaining the finan-
cial viability of these services is essential to overall institutional financial perfor-
mance. To help in proving this point, consultant services can do the following:

1. Become involved in billing processes. Because centralized billing depart-

ments often place a lower priority on psychiatric billing than on more
lucrative surgical and procedure-based reimbursements, a psychiatric
consultation service must have direct input into its inpatient and outpa-
tient billing processes.
2. List all diagnoses. For each consult, a consultant should list all appropriate
medical and psychiatric diagnoses and document specific diagnostic cri-
teria for each major psychiatric diagnosis made.
3. Rate complexity. The consultant should keep in mind that the complexity
of the case, number of diagnoses, amount of time spent, and amount of
information included in the note may significantly alter the level of bill-
ing submitted for an initial consult or specialty evaluation.
4. Work with administration. The PM service chief should work closely with
hospital administration to define and document sources of cost savings
produced by the consultation service.
 Effective Psychiatric Consultation 7

Characteristics of
Effective Psychiatric Consultants

1. Respond promptly to consultation requests. Do today’s work today.

2. Establish the level of urgency: emergent, urgent, or routine.
3. Determine the center of gravity of the case. Having time to address compre-
hensively all biopsychosocial issues a patient may have, especially in in-
patient settings, is rare.
4. Be flexible. Perform consultations in both inpatient and outpatient set-
tings.
5. Respect patients’ rights to know that the identified “customer” is the consulting
physician.
6. Review medical data and spend time collecting essential information. Help-
ful information sources include the medical record, physicians, nurses,
family, friends, and caregivers.
7. Use the biopsychosocial model. Consider patients’ predispositions, precipi-
tants, and strengths.
8. Make a well-reasoned differential diagnosis. Consider medical, neurologi-
cal, and psychiatric syndromes.
9. Avoid not otherwise specified (NOS) diagnoses. They usually do not convey
helpful or specific information.
10. Make specific recommendations that are brief, goal oriented, and free of
psychiatric jargon.
11. Discuss findings and recommendations with consultee physicians in person
whenever possible.
12. Follow up with a patient in the hospital until the goals of the consultation
have been met, and arrange outpatient care when indicated.
13. Respect boundaries. Do not take over aspects of the patient’s medical care
unless asked to do so.
14. Read medical journals, and remain part of the medical community.
15. Educate medical administrators about cost-offset advantages of psychiatric
consultation.
16. Work with the business office and staff to optimize reimbursement.
8 Clinical Manual of Psychosomatic Medicine

Approach to Consultation
Consultation Style
Structured Versus Unstructured Interview Styles
Structured versus unstructured interview styles are not mutually exclusive,
and both are necessary to obtain valuable longitudinal and cross-sectional in-
formation. The relative merits of an open-ended interview versus a structured
clinical examination are debated (Shakin Kunkel et al. 2002).
Structured examination is necessary for some historical data and for parts
of the mental status examination.

Value of Listening and Observing

Simply listening and observing provide much information needed to make a
diagnosis and a biopsychosocial formulation. Use open-ended questions, such
as the following:

• “What brings you into the clinic?”

• “How has this illness affected your life?”
• “Why do you think your doctor asked the psychiatrist to see you?”

Patient Confidentiality
Psychiatric consultation is a new experience for many patients. Many patients
have never seen a psychiatrist before, did not request the consultation, and in
the inpatient setting, may not have been informed about the consultation.
The patients need to be made aware of confidentiality issues.

Confidentiality Limits
Confidentiality has limits in the consultation setting. Maintaining absolute
doctor-patient confidentiality is not possible for a psychiatric consultant (Si-
mon and Walker 2002), because the physician requesting the consult is the
identified “customer” and expects an answer to the consultation. The best ap-
proach is to explain this dual relationship to the patient from the start.

Sharing of Medical Records

Medical records are read by others. The outpatient or inpatient medical record
is a relatively public document. Notes regarding consultation visits are avail-
 Effective Psychiatric Consultation 9

able not only to the referring physician but also to other providers in the
health care system.
The Health Insurance Portability and Accountability Act (HIPAA) in-
creased document protection requirements in health care settings. Particular
care should be taken to satisfy these requirements when considering transmit-
ting patient information via fax or electronic means (Office for Civil Rights
2002).

Patient Follow-Up
Patients should be followed up until the goals of consultation are met. Psychi-
atric consultants generally should follow up patients until they are discharged
from the hospital or clinic or until the goals of the consultation are achieved.
This is necessary for three reasons:

• Urges to “sign off ” on patients are sometimes related more to negative reactions
toward patients than to resolution of the presenting symptoms.
• Symptoms can evolve and recur. Premature sign-off creates a potential loss of
credibility and may lead to reconsultation.
• Follow-up enhances credibility. Follow-up instills confidence that the con-
sulting psychiatrist is available and willing to help.

The frequency and duration of psychiatric follow-up will vary depending

on patient needs and financial circumstances (Simon and Walker 2002):

• Focused consultation. Many patients benefit from a single consultation

visit, consisting of management recommendations to the consulting phy-
sician.
• Brief intervention period. Some patients need a brief intervention or fol-
low-up, followed by referral back to the referring specialty or primary care
physician.
• Transfer to a specialty mental health setting. Other patients need transfer to
specialty mental health care clinics or units, for ongoing follow-up.
• Shared follow-up or team management. In many situations, a period of
shared follow-up with an outpatient physician or team allows for contin-
ued involvement and learning.
10 Clinical Manual of Psychosomatic Medicine

Outpatient Psychosomatic Medicine

Consultation Models
Traditional Outpatient Consultation
An outpatient primary care physician or specialist may ask a psychiatric consult-
ant to see a patient regarding one or more specific questions. The consultant
may see the patient once or for one or two follow-up visits to help “right the
ship,” with the expectation that the referring physician will resume overall care
of the patient after the consultation or brief intervention. Occasional patients
will need ongoing follow-up in an outpatient general psychiatry or PM practice.

Collaborative Consultation
Teams of PM psychiatrists, health psychologists, psychiatric nurses, and mental
health allied health providers can provide collaborative team care for patients
referred for consultation (Rundell et al. 2008). These teams work out of a men-
tal health clinic, can discuss cases, see patients together or see patients consec-
utively, and conduct brief interventions. Having nurses and allied health
providers collect basic historical information can increase efficiency and im-
prove financial performance without detracting from patient or consultee sat-
isfaction (Rundell and Seime 2008).

Integrated Care
Primary Care Settings
Teams of case managers, primary care physicians, and PM psychiatrists work
together in primary care systems to detect and manage depression and other
psychiatric disorders. Education, behavioral activation, antidepressants, and
brief focused psychotherapy (problem-solving treatment) are used to manage
the disorders before patients need specialty mental health treatment settings
or programs. These programs deliver long-term benefits, better function, and
enhanced quality of life for patients (Hunkeler et al. 2006).

Specialty Care Settings

PM psychiatrists often participate in integrated teams in specialty care outpa-
tient settings and programs (Rundell et al. 2008). These specialty and subspe-
cialty teams are becoming more common in major medical centers. Financial
 Effective Psychiatric Consultation 11

arrangements, which have to be negotiated with sponsoring clinical services,

are often favorable when compared to fee-for-service consultation reimburse-
ments. Examples of specialty care integrated teams include transplantation,
bariatric surgery, oncology, women’s health, infertility, dermatology, move-
ment disorder, dementia, and rehabilitation services.

References
Druss BG, Rosenheck RA: Patterns of health care costs associated with depression and
substance abuse in a national sample. Psychiatr Serv 50:214–218, 1999
Eaton JS Jr, Goldberg R, Rosinski E, et al: The educational challenge of consultation-
liaison psychiatry. Am J Psychiatry 134 (March suppl):20–23, 1977
Hall RCW, Rundell JR, Popkin MK: Cost-effectiveness of the consultation-liaison ser-
vice, in The American Psychiatric Publishing Textbook of Consultation-Liaison
Psychiatry: Psychiatry in the Medically Ill, 2nd Edition. Edited by Wise MG,
Rundell JR. Washington, DC, American Psychiatric Publishing, 2002, pp 25–32
Hunkeler EM, Katon W, Tang L, et al: Long term outcomes from the IMPACT ran-
domised trial for depressed elderly patients in primary care. Br Med J 332:259–
263, 2006
Kathol RG, Kunkel EJ, Weiner JS, et al: Psychiatrists for medically complex patients:
bringing value at the physical health and mental health/substance-use disorder
interface. Psychosomatics 50:93–107, 2009
Levenson JL, Hamer RM, Rossiter LD: Relation of psychopathology in general med-
ical inpatients to use and cost of services. Am J Psychiatry 47:1498–1503, 1990
Lipowski ZJ, Wise TN: History of consultation-liaison psychiatry, in The American
Psychiatric Publishing Textbook of Consultation-Liaison Psychiatry: Psychiatry
in the Medically Ill, 2nd Edition. Edited by Wise MG, Rundell JR. Washington,
DC, American Psychiatric Publishing, 2002, pp 3–11
Office for Civil Rights, Department of Health and Human Services: Standards for privacy
of individually identifiable health information: final rule. Fed Regist 67:53182–
53273, 2002
Rundell JR, Seime R: Comparison of an integrated, multidisciplinary outpatient psy-
chosomatic medicine assessment model with traditional outpatient consultation.
Poster presented at the annual meeting of the Academy of Psychosomatic Medi-
cine, Miami, FL, November 2008
Rundell JR, Amundsen K, Rummans T, et al: Toward defining the scope of psychoso-
matic medicine practice: psychosomatic medicine in an outpatient, tertiary-care
practice setting. Psychosomatics 49:487–493, 2008
12 Clinical Manual of Psychosomatic Medicine

Saravay SM, Lavin M: Psychiatric comorbidity and length of stay in the general hos-
pital: a review of outcome studies. Psychosomatics 35:233–252, 1994
Shakin Kunkel EJ, Monti DA, Thompson TL II: Consultation, liaison, and adminis-
tration of a consultation-liaison psychiatry service, in The American Psychiatric
Publishing Textbook of Consultation-Liaison Psychiatry: Psychiatry in the Med-
ically Ill, 2nd Edition. Edited by Wise MG, Rundell JR. Washington, DC, Amer-
ican Psychiatric Publishing, 2002, pp 13–23
Simon GE, Walker EA: The primary care clinic, in The American Psychiatric Publish-
ing Textbook of Consultation-Liaison Psychiatry: Psychiatry in the Medically Ill,
2nd Edition. Edited by Wise MG, Rundell JR. Washington, DC, American Psy-
chiatric Publishing, 2002, pp 917–925
Worley LLM, Levenson JL, Stern TA, et al: Core competencies for fellowship training
in psychosomatic medicine: a collaborative effort by the APA Council on Psycho-
somatic Medicine, the ABPN Psychosomatic Committee, and the Academy of
Psychosomatic Medicine. Psychosomatics 50:557–562, 2009
 2
Medicolegal Issues

We begin this chapter with a legal disclaimer: The authors of this book are
not lawyers, and the information in this chapter does not constitute legal ad-
vice. The views expressed in this chapter come from clinically active psycho-
somatic medicine (PM) psychiatrists, not legal experts. Laws vary from state
to state, legal precedents change, and hospitals have their own policies (e.g.,
do-not-resuscitate orders). Therefore, clinicians must become familiar with
pertinent general legal concepts, state laws, and hospital policies.
No substitute exists for good faith, common sense, excellent documenta-
tion, and a high standard of medical care (Shouton et al. 1991; Wright et al.
1996). Core competencies delineated by PM professional organizations em-
phasize that a high degree of knowledge about confidentiality, capacity, and
other medicolegal concepts is an expected skill and competency of a PM psy-
chiatrist (Bronheim et al. 1998; Worley et al. 2009). At times, however, a cli-
nician might find it helpful or necessary to consult an attorney who under-
stands the legal implications of these concepts as they apply to medical practice.

Definitions

• Advance directives—health care documents (i.e., living will, durable power

of attorney, or health care proxy) executed by competent individuals to

13
14 Clinical Manual of Psychosomatic Medicine

state their health care preferences and values and/or to designate substitute
health care decision makers in the event of future incompetence.
• Capacity—a clinician’s determination, through examination, that an adult
patient has the ability to understand and participate in decisions regarding
his or her medical care.
• Confidentiality—ethical and legal duty not to disclose information ob-
tained in the course of evaluating or treating the patient without the pa-
tient’s express or implied permission.
• Guardianship—appointment by the court of a person to be legally respon-
sible for the care and management of an incompetent person. (In most ju-
risdictions, a conservator is granted control of the individual’s estate, whereas
a guardian is granted control of the individual’s person, or body.)
• Health Information Portability and Accountability Act (HIPAA)—federally
codified set of standards with safeguards to protect privacy of patients and
their health records.
• Incompetency—a court determination that a patient lacks the mental ca-
pacity to understand the nature of an act.
• Informed consent—voluntary agreement by a competent person after full
disclosure of facts needed to make a decision.
• Right to refuse treatment—the right to determine what is or is not done to
one’s body (also called the right of self-determination).
• Seclusion and restraint—interventions that involve isolating the patient
and/or use of physical or chemical immobilization.

Patient Confidentiality
Impact of HIPAA
Trust between a patient and physician is the foundation upon which a shared
healing aim is built. HIPAA (Mermelstein and Wallack 2008; Office for Civil
Rights 2002) has codified standards related to protection of patient privacy
and confidentiality of inpatient and outpatient health records. These federal
standards have had a significant impact on the practice of medicine in general
and on the practice of consultation in particular (Mermelstein and Wallack
2008). A patient has the right to have confidential communications withheld
from outside parties unless he or she gives written authorization to release that
 Medicolegal Issues 15

information (but there are exceptions, as noted in “Statutory Exceptions to

Confidentiality” below).

Balance Patient Privacy Against Consultee Need to Know

Consultation work requires a balance between safeguarding patient privacy
and answering a consultee physician’s questions. This work is unique in that
the patient is not the primary customer. Once a consult is generated, the an-
swer is given to the consultee. The consultee can accept or reject the opinion
and recommendations of the consultant. In this balancing act, the consultant
should do the following:

1. Discuss flow of information. Consulting psychiatrists should be clear with

patients at the beginning of the consultation about the flow of information.
2. Communicate on a “need-to-know” basis. Psychiatrists do not have the au-
thorization to speak to hospital staff members about all matters revealed by
the patient (Simon 2002). Psychiatrists should only provide information
sufficient to enable the staff to function effectively on the patient’s behalf.
Rarely is it necessary to disclose intimate details about the patient’s life.

Obtain Patient Permission Before Speaking With

Family or Friends
A psychiatrist performing a consultation should not speak to a patient’s family
or significant other without the patient’s permission. Fortunately, the patient’s
refusal to allow the physician to contact the family or significant other is un-
common. If the patient refuses, the patient’s reasons should be documented in
a clear note in the medical record.

Statutory Exceptions to Confidentiality

Although laws and regulations vary from one jurisdiction to the next, there are
general exceptions to the absolute right to confidentiality (Simon 2002; Si-
mon et al. 2005). These include the following:

• Child abuse
• Competency proceedings
• Court-ordered examination
16 Clinical Manual of Psychosomatic Medicine

• Danger to self or others

• Patient as a litigant
• Civil commitment proceedings
• Appropriate communications with other health care providers involved in
the patient’s care

Informed Consent and Right to

Direct Medical Treatment
Definition of Informed Patient
Informed consent requires an informed patient. An informed patient is one
who can understand the information provided and is capable of making a rea-
soned judgment about the treatment or procedure, regardless of whether oth-
ers agree with the decision.

Exceptions to Informed Consent Requirement

Emergencies
When the physician administers appropriate treatment in a medically emer-
gent situation in which the patient or other people are endangered, and when
obtaining either the patient’s consent or that of someone authorized to pro-
vide consent for the patient has proved impossible, the law typically “pre-
sumes” that consent was granted. This presumption is not universal, however,
and there are exceptions, such as when a Jehovah’s Witness patient plainly re-
fuses a blood transfusion (Ferrando et al. 2010).

Incompetency
Only a competent person can provide informed consent. When the patient
does not have the capacity to provide consent, it is obtained from a substitute
decision maker.

Therapeutic Privilege
This exception is the most difficult to apply. Informed consent is not required
if a psychiatrist, usually in concert with the consultee, determines that a com-
plete disclosure of possible risks and alternatives might have a deleterious ef-
 Medicolegal Issues 17

fect on a patient’s health and welfare. This may not be a common clinical
event in a consultation-liaison setting. The clinician should do the following:

• Carefully document the rationale supporting this determination.

• Consider obtaining a second opinion from a respected colleague.

Waiver
A patient may voluntarily waive his or her right to information (e.g., the pa-
tient does not want information on possible negative surgical outcomes).

Signing Out Against Medical Advice

Leaving a hospital or emergency department against medical advice (AMA) is
the right of any competent patient, as long as he or she understands the nature
and consequences of the act (Groves and Vaccarino 1987). AMA discharges
constitute about 1% of all hospital dismissals. They commonly occur when
patients are experiencing conflict in the doctor-patient relationship, are too
anxious about their medical condition or treatment to engage in the treat-
ment, have personal or work pressures to leave the hospital, or have an addic-
tive disorder that has not been adequately diagnosed or treated in the hospital
(e.g., nicotine withdrawal or cocaine craving). The clinician should do the fol-
lowing:

1. Understand that the standard of capacity to sign out AMA will vary depend-
ing on the risk-benefit ratio in a particular situation.
2. Look for communication problems. A threat or an attempt to sign out AMA
often signifies a communication problem between the patient and the
staff. Patients who leave AMA often return to the hospital if the physician
has not explicitly denied further care.
3. Document patient capacity and understanding. If the patient is not a danger
to self or others and demonstrates capacity in the context of the risks in-
volved, the psychiatrist cannot do much more than try to ensure adequate
documentation.
• Request that patients sign an AMA form. A patient is requested but not
required to sign the hospital’s AMA form before departure. If the pa-
tient refuses to sign the form, the clinician should simply write on the
18 Clinical Manual of Psychosomatic Medicine

form, “Patient refused to sign form” or “Patient departed without

signing the AMA form,” and then sign and date the document.
• Document the circumstances in the medical record. Regardless of whether
the patient signs an AMA form, the situation should be documented
in the medical record, along with the annotated AMA form, detailing
the recommendations made to the patient about further hospitaliza-
tion and the possible risks of premature discharge.

Do-Not-Resuscitate and Do-Not-Intubate Orders

Patients who require cardiopulmonary resuscitation (CPR) or intubation to
support breathing in a respiratory arrest usually have not thought about or ex-
pressed a preference about its use, and others have no time to think about the
consequences of reviving a patient at the time of a cardiac arrest. Ideally, pa-
tients will have signed do-not-resuscitate (DNR) or do-not-intubate (DNI)
orders before the necessity arises.

Exceptions to DNR and DNI Orders

A competent patient has the right to reject resuscitative treatment. That right
is rarely overruled (Simon 2002; Simon et al. 2005), except in specific or nar-
row circumstances, including the following:

1. When rights of a spouse or child take precedence. At times, the rights of a de-
pendent spouse or child are considered more important than the patient’s
decision (Miles et al. 1982).
2. When the DNR and DNI orders are not available and the emergency pro-
viders are unsure what the status is. In a review of medical incident reports
in which emergency medical services were called to long-term care facil-
ities, resuscitation was attempted in 21% of residents who had requested
DNR status (Becker et al. 2003).
3. When a cardiopulmonary arrest occurs during hemodialysis. In such cases,
resuscitation may be attempted in some hospitals even when a DNR or-
der exists (Ross 2003).
4. When families or guardians intervene legally. When a competent patient ei-
ther requests or declines resuscitation and later becomes incompetent, a
court may be required to reverse the patient’s original decision (Miles et
al. 1982). In some states, the family or significant other, physician, and/or
 Medicolegal Issues 19

hospital ethics committee can intervene to resuscitate the patient if a

chance of recovery exists.
5. When a patient is deemed to lack capacity. If a patient has a major mental
disorder (e.g., severe depression) and rejects resuscitation because he or
she desires death as an “appropriate deserved” outcome, the patient is
considered to lack capacity (Simon 2002; Simon et al. 2005). The con-
sultant in this type of case would recommend that the family or signifi-
cant other seek guardianship.

Documentation of DNR and DNI Orders

DNR and DNI orders should be documented in a physician order at each ad-
mission. DNR and DNI orders are typically recorded as a physician order, and
the date, time, and reasons for the order are documented in the chart. Hospi-
tal CPR, DNR, and DNI policies vary considerably. Hemphill et al. (2004)
studied all admissions for intracerebral hemorrhage in nonfederal hospitals in
California over 2 years (N=8,233) and found that the percentage of patients
with DNR orders varied from 0% to 70% across hospitals.

Advance Directives
The Patient Self-Determination Act requires all hospitals, nursing homes, hos-
pices, managed care organizations, and home health care agencies to advise pa-
tients or family members of their right to accept or refuse medical care in the form
of an advance directive (Simon 2002; Simon et al. 2005). A living will is an ex-
ample of an advance directive. This law also states that a hospital must, if it wishes
to receive Medicare and Medicaid payments (Greco et al. 1991), do the following:

1. Develop policies about advance directives.

2. Ask all patients admitted to the hospital if they have advance directives
and enter those into the chart.
3. Give patients information about advance directives.
4. Educate the staff and community about advance directives.

Power of Attorney
Definition
A durable power of attorney empowers a trusted family member or other agent to
make health care decisions. This document is much broader and more flexible
20 Clinical Manual of Psychosomatic Medicine

than a living will, which covers just the period of a diagnosed terminal illness and
specifies only that no extraordinary treatment be used to prolong life.

Revoking or Overriding a Power of Attorney

A patient may revoke a power of attorney document or a health care proxy,
sometimes even when reasonable evidence indicates that the patient is incom-
petent (Simon 2002; Simon et al. 2005). If the patient is grossly confused and
is an immediate danger to self and others, the physician is on firm medical and
legal ground to temporarily override a patient’s treatment refusal if it varies
from written wishes or directions expressed by a designated power of attorney.
Generally, however, it is better to seek a court order for treatment than to risk
legal entanglement by attempting to enforce an advance directive’s original
terms if a patient has expressed the desire to revoke it.

Capacity
Competency Versus Capacity
In general, competency refers to some minimal mental, cognitive, or behavioral
ability, trait, or capability required to perform a particular legally recognized
act or to assume a legal role (Simon 2002; Simon et al. 2005). Determination
of incompetency is a judicial decision, whereas incapacity refers to a clinical
opinion that is rendered by a consulting psychiatrist (or other clinician) (Leo
1999; Mishkin 1989). Evaluation of capacity is a core skill of PM psychiatrists
(Worley et al. 2009). Consultations to “evaluate competency” are actually
evaluations for capacity.

• Incapacity does not prevent treatment. It merely means that the clinician
must obtain substitute consent on the patient’s behalf.
• The determination of capacity is not an all-or-none phenomenon. For exam-
ple, a patient may be judged incompetent by the court to manage financial
affairs but still may be considered competent to refuse a medical proce-
dure.
• Most patients are found to have capacity when capacity has been questioned
(Farnsworth 1990; Mebane and Rauch 1990).
 Medicolegal Issues 21

• Most capacity consults are requested because a patient refuses treatment or

disposition (e.g., transfer from the hospital to a nursing home) or threat-
ens to leave the hospital AMA (Farnsworth 1990; Masand et al. 1998; Me-
bane and Rauch 1990).
• Some capacity consults are to confirm a patient’s capacity to give informed con-
sent. Because the patient’s mental status can change from one hour to the
next, repetitive examinations are often necessary.

Elements of Capacity Evaluation

A flexible approach to assessment of capacity is important for the consultation
psychiatrist to understand and apply (Roth et al. 1977; Simon et al. 2005).
The matrix commonly used to organize the elements of capacity evaluation
has stood the test of time and is still valid. It is based on two variables:

1. The treatment’s risk-benefit ratio

2. The patient’s decision regarding treatment

Capacity Threshold
Capacity can be evaluated at different thresholds, depending on the patient’s
clinical situation (Magid et al. 2006).

High Threshold to Establish Capacity

Patient refuses low-risk, high-benefit intervention. For example, a patient has a
gangrenous leg, and amputation is proposed to save the patient’s life. The dan-
ger (potential risk) of this procedure to the patient is relatively low, and the ben-
efits are high. Therefore, if the patient refuses amputation, a rigorous (high)
threshold to establish capacity is applied. Failure to pass this competency test,
indicating that the patient lacks capacity, would lead the psychiatrist to recom-
mend that the physician and the patient’s family or significant other pursue
court action to appoint a surrogate decision maker.
Patient consents to a high-risk intervention with low or high benefit. Consent
to a heart transplant requires a stringent (high) threshold to establish compe-
tency because of the high mortality and morbidity associated with the proce-
dure.
22 Clinical Manual of Psychosomatic Medicine

Low Threshold to Establish Capacity

Patient consents to low-risk, high-benefit intervention. If the patient consents to
amputation, a lenient (low) threshold to establish competency is used.
Patient refuses high-risk, low-benefit intervention. If a patient declines a sur-
gical procedure that is quite risky (e.g., a Whipple procedure in a patient with
pancreatic cancer), a lenient (low) threshold to establish competency is ap-
plied.

Capacity Documentation
Documentation of capacity should be precise. The clinician should write ex-
act quotations in the medical record whenever possible, especially if the pa-
tient is refusing potentially life-saving or life-altering treatment. In some cases,
the clinician may want a witness present who can verify that the details of the
interview were reported accurately in the medical record.
Documentation of cognitive examination is necessary but not sufficient.
Impairment on a mental status examination (e.g., a Mini-Mental State Exam-
ination score of 18) is insufficient to declare a patient incompetent to make
medical decisions. Such tests measure cognitive ability, not the ability to make
decisions (Leo 1999). The consulting psychiatrist should use open-ended
questions (e.g., “Tell me about your current medical condition”), avoid yes-no
questions, and pursue or clarify vague answers.
The clinician should document patient understanding about the decision.

• Does the patient understand the current medical condition?

• Can the patient discuss the expected course of the medical condition, with
and without treatment?
• Does the patient articulate an understanding about the recommended
treatment and the risks and benefits of treatment?
• Does the patient understand the alternatives, when appropriate?

Encourage Documentation of Wishes

While Patient Has Capacity
When the chance of future incompetency is high (e.g., when a patient has
Alzheimer’s disease or cancer with brain metastasis), the consulting psychia-
trist should urge the patient and family or significant other to discuss the pa-
 Medicolegal Issues 23

tient’s preferences. The patient, while still competent, can prepare a living will
or a durable power of attorney.

Guardianship
Legal Establishment of Substitute Decision Maker
For individuals who are judicially determined to be unable to act for them-
selves, guardianship establishes a substitute decision maker (Leo 1999). In gen-
eral, the appointment of a guardian is limited to situations in which the
individual’s decision-making capacity is so impaired that he or she is unable to
care for personal safety or provide necessities such as food, shelter, clothing, and
medical care, and the impairment is considered permanent. Some states have a
provision for emergency or temporary guardianship (e.g., 60 or 90 days), after
which a second judicial hearing is conducted to determine whether to remove
the guardianship or convert it to permanent status.

Standard of Proof for Incompetency

The standard of proof required for a judicial determination of incompetency
is clear and convincing evidence. Although the law does not assign percent-
ages to proof, clear and convincing evidence is in the range of 75% certainty
(Simon 2002; Simon et al. 2005). The process required to adjudicate incom-
petence and assign a guardian can be burdensome, costly, and lengthy (Bur-
russ et al. 2000).

Specific Versus General Guardianship

A specific guardian is authorized to make decisions about a particular subject
area, such as major or emergency medical procedures. A general guardian, by
contrast, has total control over another individual’s person, estate, or both
(Sales et al. 1982).

Choice of Guardian
Clear advantages are associated with having a family member as the substitute
decision maker (Leo 1999). First, appointment of a family member as guard-
ian maintains the integrity of the family unit and relies on those who are most
likely to know the patient’s wishes. Second, this arrangement is more efficient
24 Clinical Manual of Psychosomatic Medicine

and less costly. Having a family member as guardian is not always possible,
however. Sometimes no family member is available, or family members prefer
not to play that role. In rare cases, there may be grounds for concern that a
family member will exploit the responsibility; in such situations, the court
may determine that an incompetent person’s best interests will be served by
appointment of a guardian ad litem, commonly an attorney, social worker, or
certified public advocate.

Involuntary Hospitalization
Substantive Criteria for Statutory Commitment
There are three main substantive criteria for statutory commitment (although
some states have additional provisions). An individual must be determined to
be one or more of the following (Simon 2002; Simon et al. 2005):

• Mentally ill
• Dangerous to self or others
• Unable to provide for basic needs (i.e., gravely disabled)

Legal Commitment
Commitment is a legal decision, not a medical one. Clinicians do not legally
commit patients; only a court can do that. A consulting psychiatrist merely
initiates a medical certification that brings the patient before the court, which
usually occurs after a brief evaluation in the hospital (Simon 2002; Simon et
al. 2005).

Role of Consulting Psychiatrist in

Involuntary Holding of Patients
Consulting psychiatrists must play an active role when patients are held in-
voluntarily in a medical or surgical unit. Two types of patients are held invol-
untarily in these units: 1) patients who may or may not have a psychiatric
disorder but require involuntary medical treatment because they lack capacity
to refuse it and 2) patients being held for psychiatric reasons (e.g., an overdose
patient is recovering in an intensive care unit until he or she can be transferred
to inpatient psychiatric care). In the latter circumstance, patients cannot be
 Medicolegal Issues 25

transferred immediately to a locked psychiatric unit to be held for evaluation.

Consulting psychiatrists must play active roles in educating the physicians and
nursing staff of a medical or surgical unit regarding procedures related to
safely holding patients for further evaluation, which may lead to a commit-
ment hearing.

Involuntary Hospitalization and Commitment Laws

Laws governing involuntary hospitalization and commitment vary from state
to state. A psychiatrist providing consultations to other physicians needs to be
knowledgeable about local commitment laws and procedures, as well as local
mental health treatment resources. For example, states have different laws and
regulations that govern how long a patient may be held for a safety evaluation
in preparation for a legal commitment hearing.

Seclusion and Restraint

Safety of Patient and Others
Legal and ethical expectations are that the minimum amount of seclusion and
restraint should be used to protect the safety of patients and staff. Courts hold
that seclusion and restraint are appropriate only when a patient presents an
imminent risk of harm to self or others and when a less restrictive alternative
is not available (Simon 2002; Simon et al. 2005).

Documentation Requirements
Documentation requirements are precise and not negotiable. Every hospital
actively monitors and strives to minimize restraint and seclusion. Seclusion and
restraint must be implemented by a written order from an appropriate medical
official. Because jurisdictions and hospitals may vary in implementation pro-
cedures, psychiatrists need to be thoroughly familiar with local policies.

1. The examining physician must document the following:

• Reasons for seclusion or restraint
• Details of the patient’s behavior
• Details of the examination
• Types of restraint needed (e.g., two-point, waist-belt, vest, medication)
26 Clinical Manual of Psychosomatic Medicine

2. Orders must be confined to specific, time-limited periods.

• The patient’s physical and mental condition must be regularly re-
viewed and documented.
• Extension of the original order must be reviewed and reauthorized.

Prescribing Medications for

Nonapproved Uses
Absence of a U.S. Food and Drug Administration (FDA) indication does not
necessarily mean that no evidence base exists for the use of a drug for a specific
clinical reason. The FDA evaluates only the clinical indications requested by a
pharmaceutical company. Failure to indicate other uses typically means that the
FDA did not receive a request to review related data. The FDA applies the prin-
ciple that good medical practice requires that a physician prescribe medication
according to the best information available. Prescribing an FDA-approved med-
ication for a nonapproved purpose does not violate federal law (Macbeth et al.
1994). However, the physician who deviates from approved FDA indications
has a responsibility to document the rationale for the practice.
Consultation psychiatrists frequently recommend or prescribe medications
for uses not approved by the FDA. For example, no drug is currently approved
by the FDA for the treatment of delirium; however, several drugs, mainly anti-
psychotics, are used. Prescribing drugs for nonapproved uses should be based
on sound knowledge of the drugs, firm scientific rationale, and medical data
(Simon 2002; Simon et al. 2005).
The threshold for informed consent is heightened when a medication is
prescribed for a nonapproved use. The situation is often urgent, and the patient
may lack capacity. Recommendations to administer drugs for nonapproved in-
dications require documentation of patient or family education and a rationale
for the recommendation. Many hospitals have developed algorithms or clinical
protocols for treatment of conditions such as delirium, based on evidence-sup-
ported clinical practice guidelines. These protocols help standardize clinical
practice and may buttress clinicians’ medicolegal status when prescribing drugs
for nonapproved indications.
 Medicolegal Issues 27

Malpractice
Documentation
Documentation is important when malpractice is alleged. When a medicole-
gal issue arises or might arise at some future time, detailed documentation in
the patient’s medical record is of paramount importance. Fear that the patient
will read the record should not preclude documentation. In fact, the consul-
tation and notes should be written with the expectation that the patient will
read the medical record.

Establishing Malpractice
Four elements are necessary to establish malpractice. Each involves the con-
sideration of a question.

1. The standard of care can be established. Would a reasonable, careful, and

prudent physician behave in the same or a similar way?
2. The physician breached the standard of care. Did the physician breach that
standard of care in this specific case?
3. The patient sustained an injury. Was the patient demonstrably injured?
4. The physician’s behavior caused the injury. Did the physician’s unreason-
able, careless, or inappropriate behavior cause that injury?

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 3
Mental Status and
Cognitive Examination

The mental status examination (MSE) is the psychiatrist’s stethoscope; alert

observation before, during, and after an evaluation of the patient yields a re-
flection of mind and body function that is indispensable to accurate diagnosis
and effective care. MSE results are best understood when placed in the context
of the patient’s history and recent behavior, physical and neurological exami-
nation, laboratory data, and collateral information. The MSE is multifaceted
in that some elements rely on astute observation, whereas others are drawn
from the patient’s self-report, and some portions are informal and less struc-
tured, whereas others rely on formal, structured questions or tasks. Framing
the examination in two general categories, the noncognitive and the cognitive,
can also be helpful, although there are areas of overlap.

Noncognitive Elements
of Mental Status Examination
General Appearance and Behavior
The MSE begins the moment the clinician sees the patient. The patient’s
physical appearance—including grooming, dress or lack thereof, posture,

31
32 Clinical Manual of Psychosomatic Medicine

mannerisms, and behaviors such as eye contact, facial expression, increased or

decreased body movements, pacing, tremors, and choreiform or dyskinetic
movements—shape impressions of a patient’s demeanor and shed light on his
or her mental function and psychological state at that particular time. Obser-
vation can provide valuable corroboration of a patient’s story, or raise doubt
either when a patient demonstrates a paucity of emotional investment in the
symptoms described or when a patient denies any distress but is riddled with
nervousness. The clinician should describe observations without the use of
jargon.

Speech
Speech is disrupted by psychological factors and brain disease, particularly
when the latter involves dominant-hemisphere insults. Speech is commonly
described in terms of the following characteristics, as demonstrated by the ex-
amples provided:

• Rate—the pressured speech of the manic patient on high-dose steroids;

the retarded speech of the depressed patient
• Volume—the loud speech of the angry patient; the soft, trailing speech of
the patient with Parkinson’s disease
• Articulation—the strained, distorted sounds with which a poststroke pa-
tient strives to forge once-familiar words; the slurred speech of the intox-
icated patient; the mumbled words of a patient who hopes the examiner
will give up and leave
• Rhythm and fluency—the long latent pauses in the speech of patients who
are depressed or obsessive; the stuttering or the staccato-like bursts of
words from an anxious patient
• Prosody (i.e., vocal inflection)—the emphatic embellishments of the his-
trionic patient; the flat monotone of an individual who has suffered a right
parietal stroke
• Other abnormalities of speech—mutism (which may be a hysterical reaction
to extreme stress, an expression of catatonia, or the result of neurological
injury); aphonia or dysphonia (e.g., a patient may speak only in a hoarse
whisper, caused by ninth cranial nerve or vocal cord disease or dissociative
phenomena); paraphasias; echolalia (which can have either organic or
other origins)
 Mental Status and Cognitive Examination 33

Thought Process
Thought process is assessed by observing the patient’s speech and behavior.
When the clinician asks the patient a question, how does the patient respond?
Does the patient provide an answer that is directly responsive to the question
asked (linear and goal-directed response), or meander through a circuitous ac-
count before eventually answering (circumstantial response), or ramble ever
further afield (tangential response)? The pattern of thoughts is also an impor-
tant reflection of thought process. The patient’s thoughts may move extremely
rapidly from one idea to another (flight of ideas); may skip linking connec-
tions, leaving the listener scrambling to follow the patient’s line of reasoning
(loose associations); or may stop suddenly (thought blocking).

Thought Content
The patient’s thought content or major themes reflect the patient’s immediate
and prevailing concerns, including obsessional preoccupation, suicidal or ho-
micidal ideation, misperceptions, and irrational beliefs. The patient’s behavior
also sheds light on thought content. A patient who is reluctant to talk and acts
very suspiciously is usually paranoid, even if he or she denies it. The impor-
tance of observed behavior in the assessment of thought content is illustrated
by a patient who denies misperceptions but is seen responding to hallucina-
tions. Disorders of perception include the following:

• Illusions—misinterpretations of a real sensory experience.

• Delusions—fixed false beliefs not attributable to cultural or religious beliefs.
• Ideas of reference—incorrect interpretations that events have direct refer-
ence to oneself.
• Hallucinations—sensory perceptions in the absence of an external stimu-
lus. Hallucinatory perception can be auditory, visual, tactile, olfactory
(smell), gustatory (taste), or kinesthetic (body movement). Although cul-
tural variations occur, hallucinations that occur in an awake individual are
almost always symptomatic of a pathological process.
1. Auditory hallucinations are more typically seen in primary psychiatric
disorders.
2. Visual hallucinations are typically associated with brain dysfunction, al-
though they also occur in nonpsychiatric patients with severe recent
visual loss and in some patients with schizophrenia (Bracha et al. 1989).
34 Clinical Manual of Psychosomatic Medicine

3. Tactile hallucinations may occur during substance-induced withdrawal

delirium and are often experienced after a limb amputation. “Phantom
limb” sensation, the feeling that the amputated limb is still present, oc-
curs in most patients who undergo amputation. Over time, the tactile
hallucinations diminish and usually completely disappear.
4. Olfactory, gustatory, or kinesthetic hallucinations are rare and are most com-
monly experienced by patients with partial seizures (Lishman 1998).

Mood
Mood is the patient’s pervasive and sustained emotional state. Terms used to de-
scribe mood include euthymic, dysphoric, depressed, elevated, euphoric, expansive,
and irritable. Some clinicians record both a patient’s subjective description of his
or her mood and the physician’s objective assessment of that patient’s mood, us-
ing the patient’s conduct and demeanor throughout the examination to form a
considered judgment. (An alternate perspective to that described here is that
some clinicians define mood as the patient’s expression of how he or she feels and
affect as the objective assessment of mood by the examiner.)

Affect
Affect is to mood as weather is to climate. The parameters used to describe af-
fect—the patient’s moment-to-moment emotional states—are range, inten-
sity, lability, reactivity, and consonance or appropriateness.

• Affective range may be full (i.e., the patient shows a wide range of emo-
tional states during the interview) or narrow. The latter is sometimes dis-
tinguished as restricted when the patient’s affect is impassive or constricted
when the range is narrow but confined on the affective spectrum (e.g.,
“constricted at the dysphoric [or gleeful] end of the spectrum”).
• Affective intensity can vary greatly across patients, from the rage seen in a
patient with borderline personality disorder to the flat expression often
observed in a patient with Parkinson’s disease.
• Affective lability (i.e., extremely rapid emotional shifts) may imply a toxic
or medical etiology but is also observed in some patients with prominent
characterological struggles and bipolar disorder.
 Mental Status and Cognitive Examination 35

• Affective reactivity (i.e., the patient’s capacity to register an emotional re-

sponse, such as gratitude for empathy or a smile at shared humor) offers a
clue to thought process and content as well as available emotional energy
with which the patient engages his or immediate surroundings.
• Affect that is either appropriate or inappropriate to the topics under discus-
sion is another important observation.

Suicidality and Homicidality

Suicidality and homicidality reside in the patient’s thought content but are
commonly recorded separately for ease of reference in light of their salience. A
patient’s wish and/or subsequent ideation may be active (deliberate cognitive
engagement with the act and its consequences) or passive (e.g., thinking “If
God would take me, it would be a relief ”). The ideation, even if active, may or
may not give rise to acknowledged intent. Also, intent may or may not mature
into a specific plan, sometimes with attached contingencies. Lastly, active ide-
ation leading to intent and a plan may yet be in the planning stage or may have
already precipitated action.

Insight and Judgment

Insight is present if the patient realizes that a problem exists, that his or her
thinking and behavior may contribute to that problem, and that he or she may
need assistance. Judgment is an individual’s ability to correctly anticipate the
consequences of his or her behavior and to conduct himself or herself in a cul-
turally acceptable way. Although judgment is often inferred by the patient’s
answer to a question, such as, “What would you do if you found a stamped,
addressed envelope lying next to a mailbox?” the fact that a patient would put
the aforementioned envelope in the mailbox does not mean that judgment is
unimpaired, especially if that patient has just walked into the hospital hallway
naked and recently urinated in the corner of his room. Thus, more useful
questioning tests the patient’s judgment relevant to his or her situation, such
as asking a patient with diabetes what she would do if her glucose exceeds 400,
or asking an elderly patient who is living alone what he would do if he runs out
of medicine on the weekend. Recent behavior is the best way to gauge a pa-
tient’s judgment.
36 Clinical Manual of Psychosomatic Medicine

Cognitive Elements of
Mental Status Examination
General Considerations
Cognitive impairment occurs frequently in elderly patients who are medically
ill, especially those who are hospitalized. Unless it is severe, this impairment
often is not recognized by nonpsychiatric physicians and medical personnel
(Laurila et al. 2004). The consulting psychiatrist also may miss the cognitive
impairment if he or she depends too much on conversation during the inter-
view to identify impairments and does not formally test brain function. Just as
a cardiologist uses stress testing to reveal cardiac ischemia, the consulting psy-
chiatrist must deliberately stress brain function to confidently uncover cogni-
tive compromise. In performing an MSE, the clinician should keep in mind
several important considerations:

1. Be aware of inherent challenges. Assessing a patient’s mental status in the

hospital environment can be difficult. Hospital rooms are noisy, and pri-
vacy is often lacking. Interruptions and distractions—such as intravenous
alarms, a roommate who is groaning or loudly talking with visitors, and a
harried nurse or phlebotomist who must have immediate access to the pa-
tient—are common. In addition, the patient is ill, often frightened, and
frequently sleep deprived; sometimes, a patient has not seen a psychiatrist
before and was not told about the consultation.
2. Optimize patient performance. Before the examination begins, the psychi-
atrist should ensure that the patient has his or her usual sensory aids (e.g.,
glasses, hearing aid). Whenever possible, roommates and others, includ-
ing family members, should be asked to leave the room during the exam-
ination, thereby providing some privacy and preventing significant others
from answering for the patient when specific questions are asked.
3. Test the whole brain. Tests of right-hemisphere, or nondominant, brain
function are as important as more traditional tests of verbal function,
which are the domain of the left hemisphere. The psychiatrist who asks
the patient to remember verbal items but does not have the patient draw
and recall shapes essentially ignores testing an important part of the
brain’s function (Ovsiew 1992).
 Mental Status and Cognitive Examination 37

4. Respect the value of assessment. Residents are often tempted to sheepishly

preface a structured MSE by saying, “I just have a few silly questions for
you now. I ask everyone these questions.” Most patients are too polite to
inquire why someone would ask “silly questions” as part of a serious eval-
uation, much less ask them of everyone. Rightly understood, the ques-
tions are no more silly than an internist feeling the quality of the carotid
pulse wave or probing the depth of pretibial edema with a thumb.

Level of Consciousness and Orientation

Psychiatric consultation is often requested for patients who have a rapid or
recent change in mental status. In many instances, these patients are either le-
thargic or agitated following surgery, have developed an infection or started
taking a new medication, or have significant changes in metabolic status. In
addition to changes in arousal, such patients often have hallucinations and al-
tered thought content. The psychiatrist should gauge the patient’s situational
awareness by directly asking about orientation to self, place, and time. Inter-
vals of time are difficult for delirious or demented patients to track but can
easily be assessed by asking the patient how long he or she has been in the hos-
pital. Serial measurement of orientation provides valuable longitudinal and
treatment outcome data. The clinician should not rely on a medical chart en-
try stating “alert and oriented × 4.” That usually means that the patient is
arousable and generally cooperative; it does not mean that the patient’s orien-
tation was tested or that he or she is not delirious.

Attention
The capacity to direct and maintain one’s attention while screening out extra-
neous and irrelevant stimuli is a fundamental yet highly complex cognitive
function. Inattention (the breakdown of selective attention) and distractibil-
ity are common and clinically significant neuropsychiatric symptoms. Inat-
tention also can complicate the entire evaluation process (Mesulam 1985).
For example, an inattentive patient will frequently fail tests of memory or cal-
culation on the basis of inattention alone. Standard tests for attention include
digit span, spelling a five-letter word backward, reciting the months of the
year backward, or subtracting serial 7s (or 3s for those who cannot do 7s).
38 Clinical Manual of Psychosomatic Medicine

Language
Language disturbances, specifically aphasias, refer to defects in word choice,
comprehension, and syntax. The clinician should consider whether the pa-
tient’s language is fluent and whether the words the patient chooses form a
unified whole and make sense. Next, comprehension must be tested, which is
particularly important when a patient is on a ventilator and normal speech is
not possible. The clinician can ask yes-no questions, such as, “Do you put on
your socks before your shoes?” “Is there a tree in this room?” and “Can an ele-
phant ride a tricycle?” to establish comprehension and avoid being fooled by
an interactive but uncomprehending patient.

Memory
The clinician should ask the patient to remember four unrelated items, such as
tulip, bottle, courage, and olive. The patient should immediately repeat all
four words to ensure that he or she has properly heard, understood, and reg-
istered them. After about 3 minutes of conversation or examination, the cli-
nician should ask the patient to repeat the words. If the patient cannot recall
the words, the clinician should give the patient clues to determine whether the
words were not encoded into memory or were encoded but are difficult to re-
trieve. Patients who did not learn the words are not aided by prompting,
whereas patients who learned the words but have difficulty accessing them
usually will recall with prompting. Testing right-brain function is accom-
plished by asking the patient to copy three geometric shapes and then, after
several minutes, to draw them from memory. In some situations, the clinician
can hide three objects in the room while the patient is watching, and then ask
the patient to find them later in the interview.

Abstraction
Educational level is a strong determinant of a person’s ability to abstract. The
clinician usually conducts bedside testing by asking the patient to interpret
proverbs, such as, “The image maker does not worship the gods” or “The
golden hammer breaks the iron door.” Selecting an unfamiliar proverb is pref-
erable because it reduces the likelihood of an automatic response (Sims 2003).
The patient need not reply with a definitive interpretation, because the assess-
 Mental Status and Cognitive Examination 39

ment has more to do with the patient’s approach than with the “correctness” of
his or her answer. Concrete interpretations are more commonly given by indi-
viduals with less than a high school education, schizophrenia (whose interpre-
tations are also often bizarre), and dementia. The ability to abstract can also be
assessed more subtly by observing the patient’s response to and use of figures of
speech, analogies, and metaphors.

Screening Tools for

Bedside Cognitive Assessment
Several bedside examinations can be used to screen patients for cognitive dys-
function. For nonpsychiatric physicians who do not typically perform a formal
MSE or for medical students who are learning to treat mental status problems,
screening MSEs are useful. In addition, serial screening MSEs are often used to
follow up the clinical course of a patient with delirium, especially in response to
treatment. Also, the score obtained from a screening MSE may influence a
physician who doubts that the patient is cognitively impaired but believes
“hard data.” For the consultation psychiatrist, however, a screening MSE is
only one part of a more extensive cognitive examination.

Advantages and Disadvantages

Advantages of most bedside screening tools include the following:

• Brief time requirements (can be completed in 5–10 minutes)

• Structured format
• Simple administration and scoring
• Minimal effort required of medical patients

Disadvantages of most bedside screening tools include the following:

• Failure to identify focal deficits

• Failure to identify mild global deficits
• Dependence on education (risk of false negatives in well-educated patient
with deficits and of false positives in patients with limited education)
• False sense of security when score indicates “normal” function
40 Clinical Manual of Psychosomatic Medicine

Commonly Used Bedside Cognitive Screening Tools

Mini-Mental Status Examination
The Mini-Mental Status Examination (MMSE) is probably the most widely
used and best-known screening MSE (Folstein et al. 1975). The MMSE takes
about 5 minutes to administer, can be administered serially to monitor a patient’s
clinical course, and is a reliable and valid MSE for medical patients (Nelson et al.
1986). A score of 20 or less may indicate impairment (Folstein et al. 1975); how-
ever, Mungas (1991) proposed that scores of 0–9 correspond to severe cognitive
impairment, 10–20 to moderate impairment, 21–24 to mild impairment, and
25–30 to questionable impairment or intact function. A high score on the
MMSE is insufficient to declare that the patient has normal cognitive function.

Short Test of Mental Status

The Short Test of Mental Status (STMS) was developed to be more sensitive
than the MMSE for assessing problems of learning and recall in patients with
early and mild dementia (Kokmen et al. 1987, 1991). Additionally, the STMS
includes items that allow an improved evaluation of abstract reasoning and
mental agility in comparison with the MMSE (Tang-Wai et al. 2003).

Montreal Cognitive Assessment

The Montreal Cognitive Assessment (MoCA; available at www.mocatest.org)
is a 30-item test that can be administered in 10 minutes and was developed to
better discriminate between mild cognitive impairment and normal function
(Nasreddine et al. 2005). The MoCA also contains elements, such as a mod-
ified Trail Making Test, that help assess executive function.

Addenbrooke’s Cognitive Examination

Addenbrooke’s Cognitive Examination–Revised (ACE-R) is a detailed bed-
side cognitive screening test that requires the clinician to read from a copy of
the test during administration (Miosha et al. 2006). The ACE-R can be ad-
ministered in 15–20 minutes. The instrument, on which patients can score up
to 100 points, assesses complex language and executive function, as well as
visuospatial ability. The ACE-R is more sensitive to early deficits in Alzhei-
mer’s disease and frontotemporal dementia compared with the MMSE, and
has a role in screening patients whose results on the MMSE are ambiguous
(Mathuranath et al. 2000).
 Mental Status and Cognitive Examination 41

Other Useful Tests of Cognitive Function

The consultation psychiatrist may encounter patients for whom the adminis-
tration and interpretation of more focal cognitive tests will yield increased
diagnostic clarity. Lishman’s (1998) classic text has an excellent detailed dis-
cussion of cognitive function and psychometric tests. A few clinically helpful
examples are described below. Observing the patient while he or she attempts
to draw, calculate, name, or recall is quite informative regarding both brain
function and personality style.

Tests Requiring No Accompanying Specialized Kit

Clock Drawing Test
The Clock Drawing Test is a very useful bedside test and is part of a basic MSE.
Many examiners hand the patient a blank sheet of paper and ask the patient to
draw the entire clock, including the circle; however, patients often draw a small
circle and scribble numbers inside. This makes assessment of dyspraxia impos-
sible, especially if the patient is mildly impaired. For this reason, the clinician
might choose instead to give the patient a sheet of paper with a large circle al-
ready drawn on it and then say, “Write the numbers as if this circle is the face of
a clock.” After the patient is partially finished with the task, the psychiatrist
should interject, “When you finish, draw the hands of the clock so that the
time says 15 minutes past 10 o’clock.” The clinician can simplify the task by
naming an easier time (e.g., 3 o’clock). This task is easy to administer and is in-
structive, particularly for documenting constructional apraxia and, therefore,
early dementia (Esteban-Santillan et al. 1998) or delirium (Trzepacz et al.
2011). Visuospatial errors are more common in patients with right-hemisphere
damage; by contrast, left-hemisphere injury is more likely to result in time set-
ting errors (Tranel et al. 2008). More than a dozen methods are used to score
the Clock Drawing Test (Colombo et al. 2009). A practical bedside approach is
to observe the following principal components of the patient’s product (Freund
et al. 2005):

• Numbers. Are all 12 numbers present, inside the clock face, and without
omission or duplication?
• Spacing. Are the numbers spaced (nearly) equally from one another and
the edge of the circle?
42 Clinical Manual of Psychosomatic Medicine

• Time. Are there two clock hands that are at least approximating the in-
structed time? (Further, the patient should not resort to additional mark-
ings, such as arrows pointing to an intended number or the time written
out in digital clock format, such as “10:15.”)

Frank Jones Story

The Frank Jones story tests the patient’s ability to conceptualize a situation
and to solve a problem (Bechtold et al. 2001). The patient is asked to explain
the following story: “I have a friend by the name of Frank Jones whose feet are
so big that he has to put on his pants by pulling them over his head.” The psy-
chiatrist should watch the patient’s immediate response closely to see whether
the patient instantly smiles or appears puzzled and confused. Then the psy-
chiatrist asks the patient, “Can Mr. Jones do that?” A patient with normal cog-
nitive function will chuckle and explain in an understandable way why it is
impossible. When patients with cognitive difficulties hear the story, they often
do not laugh because they do not “get it.” They are also unable to rationally
explain their response. Patients with delirium may smile (they seem to under-
stand), but their explanations often are bizarre (e.g., “Well, maybe he can if he
unzips his fly” or “I guess so if he takes off his shoes”).

Set Test
The Set Test is an assessment of verbal fluency designed to screen elderly pa-
tients for dementia (Isaacs and Kennie 1973). The patient is asked to name 10
items from each of four categories: fruits, animals, colors, and towns. (A useful
mnemonic to recall the four categories is FACT.) The patient is asked to name
10 fruits, then 10 animals, and so on. The score is the total number of items
correctly named, with a maximum score of 40. For patients ages 65 and older,
scores lower than 15 are clearly abnormal and indicate impairment. This test
is not timed, and it should not require such patience that the examiner is
tempted to forgo its use. The Set Test is a challenging distraction after the ex-
aminer has presented four words for the patient to recall later and is a sensitive
indicator of frontal lobe dysfunction. The test also introduces the opportunity
for a patient to unwittingly demonstrate perseveration, another clue that the
patient might have frontal deficits.
 Mental Status and Cognitive Examination 43

Vigilance Test
The vigilance test (Strub and Black 1985; Wong et al. 2010) measures the pa-
tient’s ability to sustain attention. For example, the psychiatrist reads—at a
rate of one letter per second—a series of 60 letters, in which 18 are the letter
A, and the patient is asked to raise his or her hand each time the letter A is read.
Two or more errors are considered abnormal.

Tests That Require Accoutrements

Bender-Gestalt Test
The Bender-Gestalt Test (Bender 1938) examines the patient’s ability to copy
designs. During a full protocol, nine designs are presented, one at a time, and
the patient is asked to copy them. Errors suggest brain dysfunction, and error-
free performance strongly supports the absence of brain disease. Visual mem-
ory can be tested by asking the patient to reproduce the figures from memory
after a brief period has elapsed. A clinician can select and carry three or four of
these cards for bedside testing.

Blessed Dementia Scale

The Blessed Dementia Scale has two parts, which are used separately or to-
gether (Blessed et al. 1968). One part measures the patient’s ability to perform
everyday activities, and the second part measures the patient’s performance on
an information-memory-concentration test. Information about daily activities
is provided by a knowledgeable family member or close friend. The Blessed
Dementia Scale does not have a cutoff score to establish the diagnosis of de-
mentia. Instead, an increasing score correlates with worsening dementia.

The Marie Three Paper Test

The Marie Three Paper Test provides a quick assessment for comprehension
and receptive aphasia (Lishman 1998). Three different-sized pieces of paper
are placed in front of the patient. The patient is asked to take the biggest piece
and hand it to the examiner, take the smallest piece and throw it to the
ground, and take the middle-sized piece and place it in his or her pocket or un-
derneath the hospital bed pillow.
44 Clinical Manual of Psychosomatic Medicine

Trail Making Test

The Trail Making Test has two parts, each consisting of several circles distrib-
uted on a sheet of paper (Reitan 1958). In Part A, the circles contain numbers,
and the patient is asked to connect the numbers in sequence by drawing a line
as quickly as possible from one circle to the next. In Part B, each circle con-
tains either a number or a letter. The patient is asked to connect the circles, al-
ternating between numbers and letters (i.e., 1, A, 2, B, etc.). Parts A and B are
timed, and age-corrected norms are available. More than one error on either
test is usually significant.

Tests of Executive Function

The term executive function refers to an array of mental skills used to initiate,
maintain, and organize the flow of information and to coordinate actions. Ex-
amples of these processes include attention allocation, goal maintenance, and
other functions that stabilize performance. Several of the tests already men-
tioned, such as the Trail Making Test Part B, the Set Test, and the Clock
Drawing Test, are used to test executive function. The following are additional
bedside methods of assessing this critical contribution of the frontal lobes
(Kipps and Hodges 2005).

Letter and Category Fluency

To assess letter fluency, the patient is asked to list as many words as possible in
1 minute that begin with a given letter of the alphabet (F, A, and S are com-
mon examiner choices), excluding proper names and sequential word deriva-
tives (e.g., nut, nuts, nutter). A score of 15 words per letter is normal. Category
fluency is assessed by asking the patient to list as many names of animals as
possible in 1 minute. Young adults can typically list 20 animals; 15 is consid-
ered a low average score, and a score of 10 or less confirms impairment. Pa-
tients with executive dysfunction typically perform poorly in both letter and
category fluency, and individuals with subcortical or frontal pathology usually
have particular difficulty with letter fluency. By contrast, patients with Alz-
heimer’s disease are likely to have more prominent impairment with category
fluency.
 Mental Status and Cognitive Examination 45

Go–No Go Evaluation of Impulsivity

In the go–no go evaluation, the patient is instructed, “Tap your fingers [on
your lap/bed/table] once when I tap once, but do not tap at all when I tap
twice.” The examiner proceeds with a series of taps, randomly alternating sin-
gle and double taps. This challenge can be heightened by inverting the in-
structions before a second trial (i.e., telling the patient to withhold tapping in
response to a single tap of the examiner, but to tap once when the examiner
taps twice). Impulsivity is believed to indicate a failure of response inhibition.
The patient who is unable to regulate taps as instructed and instead responds
as if cued by the examiner’s activity demonstrates probable inferior frontal pa-
thology.

Cognitive Estimates
Patients with executive dysfunction do not estimate effectively and may give
unusual or even bizarre answers to estimation questions. The clinician can eas-
ily present estimation questions that give the appearance of arising naturally
from the clinician’s conversation with a patient (e.g., “Yes, this is a large hos-
pital. Big buildings are interesting. What do you think is the height of the Em-
pire State Building?” or “You mentioned you have a daughter in Dallas. How
many hours do you think it would take to drive to Detroit?”).

Similarities
Inferential reasoning is often hobbled in patients with frontal lobe impair-
ment. The examiner can evaluate this reasoning by asking the patient to ex-
plain the similarity between two conceptually equivalent objects; the task can
be made progressively more challenging by moving from obvious pairs, such
as “bananas and strawberries,” to more complicated pairs, such as “concertos
and mosaics.”

Three-Step Luria
The left frontal lobe is believed to enable motor sequencing. This executive
function can be assessed with the Luria three-step test (Weiner et al. 2011), in
which the patient is asked to demonstrate an ongoing, unbroken, three-step
sequence of a fist on the thigh, followed by an upright hand with the edge of
46 Clinical Manual of Psychosomatic Medicine

the hand contacting the thigh, followed by an open palm on the thigh, then
back to the fist, and so on. The examiner typically illustrates this sequence first
for two or three cycles to be sure the patient understands what is expected.

Neurological Examination
A basic bedside neurological examination can provide illuminating informa-
tion about any patient with cognitive dysfunction, suspected somatoform or
conversion disorder with neurological complaints, or malingering. The exam-
ination does not need to be time consuming. Often, the patient’s history sug-
gests deficits and helps focus the examination.

Basic Neurological Examination

In a basic neurological examination, the clinician should do the following:

1. Check deep tendon reflexes for symmetry. Check for the presence of a Ba-
binski reflex (extension of the great toe, with flexion and splaying of the
other toes, when the sole of the foot is firmly stroked). Some clinicians also
check for primitive reflexes (snout, grasp, glabellar, and palmomental).
2. Check muscle strength for asymmetry, weakness, tone, or embellishment.
3. Observe gait and associated arm movements, when possible.
4. Examine cranial nerve function.
5. Check the distribution of any sensory complaints.
6. Check for signs of meningeal irritation, such as neck stiffness, headache,
Kernig’s sign (inability to straighten the leg when the hip is flexed to 90 de-
grees), or Brudzinski’s sign (flexion of the hips and knees when the neck is
fixed).

Consultation Psychiatrist as Neuropsychiatrist

Knowledge of brain-behavior relationships and familiarity with neurological
terminology is useful for psychiatrists to function well as consultants in the
hospital setting. The list below contains a few commonly used neurological
terms. The prefix a- means complete loss of ability (e.g., aphasia is the loss of
 Mental Status and Cognitive Examination 47

ability to comprehend or express speech), and the prefix dys- means an im-
paired ability, as in the following examples:

• Dysarthria—disturbance of articulation of speech caused by muscle dys-

function
• Dysbulia—decrease in willpower
• Dyscalculia—impaired ability to do mathematical calculations
• Dysgnosia—impaired ability to recognize the importance of sensory im-
pressions
• Dysgraphia—impaired ability to express thought in writing
• Dyslexia—impaired ability to read
• Dysphasia—impaired ability to comprehend, elaborate, or express speech
• Dyspraxia—impaired ability to use objects correctly
• Dysprosody—impaired pitch, rhythm, and variation of speech

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 4
Personality and
Response to Illness

P ersonality is a fairly consistent but individual worldview that shapes a per-

son’s emotional experience of life and the subsequent—often predictable—set
of behaviors that characterize a person’s management of day-to-day living.
These long-term traits are generally stable and usually ego-syntonic; only a
minority of individuals have a style so inflexible and maladaptive as to cause
significant interpersonal impairment or subjective distress (i.e., a personality
disorder). In a hospital, however, two additional factors are at work. First, the
patient is obliged to interact within a confined, often unfamiliar, psychological
and literal space in which friction and collision are commonplace. Second,
even the proverbial well-adjusted person who is medically ill is confronted with
new stressors that can disturb the usual balance between needs, longings, ex-
ternal reality, and conscience. Medical illness and hospitalization present the
patient with a strange, demanding environment that may destabilize personal-
ity function. Under severe stress, many individuals regress (unconsciously, in
an attempt to “retreat” to former, more familiar, and seemingly more secure
psychological ground). Most individuals are resilient and cope well with an ill-

51
52 Clinical Manual of Psychosomatic Medicine

ness or injury, but when personality is strained and a patient’s behavior bends
beyond its usual boundaries, treatment might be complicated or the patient’s
cooperation with the medical or nursing staff might be hindered. In these cases,
the consultation-liaison psychiatrist is often called. From the patient’s perspec-
tive, the psychiatrist’s arrival may add insult to injury; the psychiatrist is unex-
pected and unwelcome in a setting with limited privacy that is already littered
with unpleasant surprises and pain, and his or her uninvited presence has un-
certain meaning.

The Person
Whether the patient has a serious acute illness prompting urgent hospital ad-
mission, has already been in the hospital for 2 months, or is referred for out-
patient evaluation in the context of a new medical diagnosis, several factors
shape the patient’s perspective on his or her situation and life when he or she en-
counters the psychiatrist. The more aware the consulting psychiatrist can be-
come of the role of these factors for an individual patient, the better equipped
the psychiatrist will be to offer the patient and the requesting physician effective
recommendations. These factors include the disease itself; the patient’s premor-
bid personality and past history; and the individual’s spiritual and existential
strengths or struggles, and the experience of illness and suffering introduced by
the disease—often molded by the presence or absence of supportive family,
friends, or other networks of support.

Nature of the Disease

Disease is no respecter of persons. Pauper or president may experience loss of
control of basic bodily functions, such as eating, sleeping, walking, breathing,
or bladder and bowel control.
The disease may be common or rare. The diagnosis may have been estab-
lished immediately and easily, or it may remain uncertain even after tertiary re-
ferral and extensive testing. The disease may be traceable in the family tree or
an unknown intruder; its boundaries may be distinct, or the disease may bring
a lifetime of uncertainty. Effects of the disease may mean that the patient can
no longer drive or can no longer bowl. Some diseases gnaw and nag, whereas
others threaten life. The effects may be unseen or may draw covert stares in
 Personality and Response to Illness 53

public. Whatever the current dimensions of the disease, for most patients,
there was a day when the disease had no place in their lives, and now their story
of life will not be complete without inclusion of the disease.

Acute Versus Chronic Disease

The disease may be acute or chronic. An acute disease presents particular in-
trapsychic challenges that cause a patient to contemplate what the disease
means for him or her at this moment and whether he or she can exert any con-
trol. Chronic disease involves additional interpersonal factors, in that the pa-
tient tries to see himself or herself through the eyes of others, including their
reactions and expectations.

Collateral Factors
Collateral factors, such as medical and toxic conditions, can independently
produce profound personality change.

• Acute conditions, particularly central nervous system insults, can either

change personality traits or magnify preexisting ones. The family of a pa-
tient with a secondary personality syndrome, for example, may report that
the patient is “not himself.” Appropriate social behavior often disappears.
Apathy, suspiciousness, affective instability, poor impulse control, and a
change in demeanor can occur.
• Chronic pain or chronic illness can lead to maladaptive chronic behavior
patterns (e.g., expectation of disappointment and rejection).
• Medications used to treat medical and neurological disease may also have
direct effects on a patient’s experience and behavior.

Personality and Past History

A patient’s behavior during times of severe stress does not necessarily reflect
long-term personality dysfunction or the presence of a personality disorder. Pa-
tients with personality disorder do not commonly seek mental health treat-
ment for the behavior itself, although they may try to find relief from the emo-
tional distress that is provoked by their style; the patterns of behavior are
ingrained, stable, and “comfortable.” More commonly, someone else, such as a
family member or hospital staff, wants the patient’s behavior to change, espe-
cially when the behavior complicates medical management. Patients with per-
54 Clinical Manual of Psychosomatic Medicine

sonality disorders also affect the physician’s and staff ’s abilities to respond ap-
propriately, leading the medical team members to demonstrate nontherapeutic
behaviors, such as avoiding the patient, not responding to a change in symp-
toms, or assigning the patient’s care to the least skilled member of the team. In
this way, countertransference can influence the patient’s clinical outcome.

• Personality patterns. Personality patterns are a mosaic of traits, in which

particular “colors” or combinations often predominate. The more com-
mon patterns are described with further detail below (see “Personality Pat-
terns of Patients”).
• Past history. Patients perceive their current medical difficulties through a
lens shaped not only by prior psychiatric illness but also by previous ex-
periences with general medical hospitalizations.

Meaning of Illness
Disease, personality, and spiritual or existential perspective each play a role in
the patient’s subjective experience of the medical plight that has pushed the
patient to a physician’s office or a hospital. One approach to assessing what
meaning the patient attributes to an illness is to review the following common
themes (Rowland 1989):

• Distance—disruption, separation, or loss of close relationships

• Dependence—necessity of relying on others for care and support
• Disability—interruption in the trajectory of life and day-to-day achieve-
ment
• Disfigurement—physical changes that distort body image and integrity
• Death—threat of final closure of personal connection with family and
friends

Personality Patterns of Patients

Personality may be viewed as a constellation of characteristic assumptions, in-
terpretive framework, and behavioral responses that emerge over time from a
person’s biological propensities, developmental context, life experience, and
 Personality and Response to Illness 55

view of the future (Ursano et al. 2002). Behaviors associated with personality
are characteristically ego-syntonic; because they feel “natural,” the individual
may not understand why his or her actions distress others. Trauma and medical
illness often induce psychological regression and can exacerbate personality
dysfunction. The following descriptions of personalities, as well as the possible
psychological factors that may drive patient behavior in the medical setting and
the common responses among medical staff, are drawn from multiple sources,
each of which will reward the reader who reflects on the original manuscript
(Geringer and Stern 1986; Groves 1978; Groves and Muskin 2011; Kahana
and Bibring 1964; Leigh and Reiser 1992; Levenson et al. 2000; Miller 2001;
Nash et al. 2009; Perry and Viederman 1981; Strous et al. 2006).

Dependent, Demanding Patients

Dependent, demanding patients communicate an urgent, intense, and persis-
tent insistence on exceptional attention to assuage their anxiety and deep un-
certainty regarding their acceptability and security. They seem to act as though
they cannot tolerate the current stress without a perpetual demonstration that
their medical team will be as omnipresent and solicitous as the imagined “per-
fect mother” of a helpless infant. Unmet demands often provoke anger, occa-
sionally depression or apathy, and less commonly a paradoxical and impulsive
demand to leave the hospital.

• Perceived threat. Patient fears being neglected, overlooked, dismissed, or

abandoned.
• Clinician response. The physician may initially feel gratified and enhanced
by the patient’s profuse expression of need and appreciation, but when the
patient’s hunger for reassurance proves insatiable, the physician may feel
overwhelmed, irritated, and angry. The physician must avoid withdraw-
ing from the patient or responding to the patient’s demands by withhold-
ing support and punitively curtailing responses. Rather, the physician is
more likely to calm the patient’s fears through neutral and judicious reas-
surance, sensible limits accompanied by clear statements of continuing
commitment to care, mobilization of other resources, and rewarding of
the patient’s efforts toward independence.
56 Clinical Manual of Psychosomatic Medicine

Orderly, Controlling Patients

Orderly, controlling patients have concluded that the vicissitudes of life, not
to mention the raw risk of impulsive or rebellious behavior, are best kept in
check by hypertrophied thinking, lest action break away and shame the
owner. Accordingly, these patients are likely to be self-disciplined, fastidious,
orderly, earnest, and given to serious concern with right and wrong. These
patients may respond to the anxious uncertainties that accompany illness by
redoubling their determination to suppress emotion, exhibit responsibility,
practice self-restraint, and find refuge in inflexible (i.e., immutably true) per-
ceptions of how details should be approached. This behavior may set the
stage for vigorous critique of perceived shortcomings by the staff.

• Perceived threat. The patient fears loss of control over life, including im-
pulses, emotions, and body (not far removed from a fear of helplessness).
• Clinician response. The physician may initially admire the patient’s appar-
ent stoic, impervious response to stress, but if the patient responds to per-
ceived impotence by obstinate complaining and contentious accusations,
the physician must avoid responding with blanket reassurances and im-
pressionistic optimism. Rather, communicating respect for the patient’s
high regard for responsibility and autonomy, the physician will reinforce
predictable routine where possible and look for opportunities to give the
patient choices to restore some sense of control. Furthermore, the physi-
cian can engage such a patient’s interest in detail and desire to understand
by offering ample data and explanation of the illness, and then enlist the
patient’s collaboration in care, such as by having the patient record specific
symptoms or responses to particular interventions. The physician should
remember to recognize the patient’s attentive participation in subsequent
encounters.

Dramatizing, Emotional Patients

Dramatizing, emotional patients unwittingly feel that a close relationship with
the physician or medical team is likely to prove more soothing than physician
knowledge and skill. Achieving an intense, idealized connection becomes im-
portant to reinforce a sense of desirability and prove one’s femininity or mas-
culinity. Female patients are often effusive and sometimes overtly seductive.
 Personality and Response to Illness 57

Male patients flirt with female nurses and physicians, perhaps peppering their
conversation with stories that exaggerate their courage or manliness. Unfortu-
nately, the patient’s eagerness for a special relationship often evokes anxiety,
discomfort, and distancing in others, and these reactions in turn serve to ag-
gravate the patient’s fear of diminishing physical appeal. In working with these
patients, the medical team members (including multiple shifts of nurses) often
find that they are of two minds: some rally to reassure these colorful, emo-
tional patients, whereas others are angered by the patients’ behavior.

• Perceived threat. The patient fears loss of attractiveness, admiration, or af-

fection.
• Clinician response. The physician may respond to the patient’s expression
of keen personal warmth with charmed interest, fascination, or attraction.
The patient often provides his or her history with flourishes that suggest
unique vitality. The impressionistic history, with a diffusion of detail, may
exasperate the physician who is striving to build a precise and sequential
clinical story. The challenge for the physician is to acknowledge the pa-
tient’s anxieties and encourage the patient to discuss his or her fears while
maintaining clear boundaries; responding with a respectful balance of per-
sonal concern and professional formality will model the reassuring stance
that the patient finds so difficult to provide for himself or herself. Further
underscoring the imperative of explicit boundaries, these patients often
have a tangled sexual or relational past and may perceive intimacy when
no such offer is intended.

Long-Suffering, Complaining Patients

Long-suffering, complaining patients often present their self-sacrificing resig-
nation to life’s adversities and disappointments with apparent humility and
modesty, but a different angle reveals a patina of exhibitionistic relief, if not
muted pleasure. Close examination may eventually reveal a propensity to will-
ingly forgo comfort, sometimes choosing service or difficulty—perhaps with
unconscious choreography—that invites misfortune. Such a patient longs for
acceptance, care, and a relationship, but at some level feels unworthy or too
guilty to receive this without purchasing it with self-sacrifice and heartache.
Accepting reassurance or, worse yet, experiencing resolution of symptoms
58 Clinical Manual of Psychosomatic Medicine

would jeopardize the economy whereby this patient negotiates the complex
relationship of affliction and gratification.

• Perceived threat. The patient fears the potential loss of deserved punish-
ment or the pleasure of pain.
• Clinician response. The physician may respond to the patient’s account of
misery and suffering with earnest efforts to comfort or frame the patient’s
tribulations in a redemptive light, only to be put off, frustrated, and pos-
sibly eventually angered by a patient who answers any encouragement or
hope with increased complaint. The unaware physician may doubt his or
her effectiveness and begin to feel as impotent as the patient’s accentuation
of unending hardship suggests. The physician who appreciates the dy-
namic at work understands that the patient who laments, “It’s not easy,
Doctor,” will successfully resist any encouragement but will find consola-
tion when the physician shares the patient’s pessimism and grimly ap-
plauds the patient’s sacrifice and perseverance. Recovery poses a deep di-
lemma for these patients, so much so that cooperation with treatment may
be undermined, either covertly or openly. The astute physician will down-
play potential treatment benefit and suggest that the treatment is an ad-
ditional burden that the patient must endure, not for his or her own sake,
but to garner some relief for concerned family members or to enable the
patient to continue to serve others sacrificially.

Guarded, Suspicious Patients

Guarded, suspicious patients are particularly fearful of being placed in a vul-
nerable position where they could, without warning, be exposed, used, or
hurt. When ill, the fundamentally suspicious person is at a particular disad-
vantage; not only does dependence on the medical team magnify this patient’s
fear of being found defenseless, but he or she cannot trust the physician to act
in the patient’s best interests and may therefore withhold relevant history. It
feels like a no-win situation for the patient, confirming his or her perspective
that the world is more often than not oppressive and persecutory, and that re-
lationships with people (i.e., physicians and nurses) are dangerous.

• Perceived threat. The patient fears that harm will result from invasive, ex-
ploitative medical care.
 Personality and Response to Illness 59

• Clinician response. The physician may try to win over such a patient with gen-
erous attention, but this effort will more likely stir the patient’s fear and guard-
edness even further, prompting the physician to become defensive when the
patient lashes out, perhaps attributing malicious motives to the medical team.
When the patient persists in quarrelsome attribution of negative intentions,
the physician may feel repeatedly accused and attacked, and thus torn be-
tween defending the team or nursing staff and overlooking the patient’s exag-
gerations and oversensitivity. The physician may ease the patient’s anxiety by
identifying perceived suspiciousness as “sensitivity,” acknowledging the pa-
tient’s criticisms by observing, “I can see how you would feel that way given
the circumstances.” Although disputing either the patient’s feelings or the per-
ceived facts that fuel the patient’s accusations is never useful, commiserat-
ing—from a distance—about the inconveniences of impersonal hospital
policies may be useful. The physician should avoid undue warmth and am-
biguity, both of which arouse distrust. A useful tactic is for the physician to ad-
vise this patient as far in advance as possible about forthcoming diagnostic
tests, being candid about details. The physician should strive for an objective,
neutral presentation of recommended procedures to avoid provoking unnec-
essary resistance when the patient concludes that a physician’s preference for
one option over another is evidence that the patient is being manipulated.

Superior, Critical Patients

Superior, critical patients see themselves as powerful, all-important, and brim-
ming with self-confidence, although some of these patients partially obscure
this reality with a feigned, patronizing humility. The inevitable jostling be-
tween such a patient’s urgent need to be superior in every domain and the loss
of an idealized body image, not to mention function, that accompanies illness
places these patients in a precarious plight. Anxious and feeling acutely endan-
gered, such patients may come across to the medical team as snobby, conde-
scending, or grandiose. They may hint that they are privy to elusive and
exclusive knowledge, and they often relish detailing their achievements and
prowess, whether physical, financial, or otherwise. Such a patient, when threat-
ened by disease, often dismisses the value of “lesser” members of the staff, so
that the patient can reinforce his or her foundering sense of grandeur by noting
that the situation can only be addressed by a senior, eminent physician.
60 Clinical Manual of Psychosomatic Medicine

• Perceived threat. The patient fears the shameful loss of self-identity as per-
fect and invulnerable.
• Clinician response. The physician may momentarily be pleased to be in-
volved in the care of a very important person, if indeed the patient is such,
but this reaction typically fades quickly and is replaced by feelings of infe-
riority as the patient “name-drops” and points out the physician’s short-
comings, whether obliquely by inquiring about particular details of the
physician’s educational pedigree or directly by noting alleged details that re-
veal substandard care. The physician’s irritation may grow to anger and an
urge to take advantage of his or her knowledge of medicine and the func-
tion of the hospital to counterattack and “trim down to size” the patient’s
entitlement. The astute physician resists this urge; reframes the patient’s
entitlement as deserving of the best advice, care, and outcome; and enlists
the patient’s adherence to treatment recommendations in the service of this
deserved prerogative. An additional challenge for the physician is to avoid
excessive humility, a quality that may be so foreign to the patient’s personal
experience that it will succeed only in awakening the patient’s fear that he
or she is under the care of an incompetent. A secure, confident physician
will comfortably create room for the patient to show off and even comple-
ment the patient’s strengths.

Seclusive, Aloof Patients

Seclusive, aloof patients give the impression of disinterest in everyday events,
preferring solitary activities and sometimes appearing socially awkward or inhib-
ited. They find solace in detachment, and their inner tranquility is best sustained
by absorption in themselves and things familiar to them, occasionally expressed
by solitary immersion in unusual fringe interests. This deep reluctance to engage
the world and risk a loss of equilibrium may translate into considerable delay in
seeking medical attention. Such patients may succeed in muting the anxiety one
expects to accompany certain diagnoses or procedures so thoroughly that they
appear conspicuously unconcerned. Close friends are few, if they exist at all, and
even family may allow that the patient has been a loner, and perhaps eccentric.

• Perceived threat. The patient fears intrusion, obligatory interaction, and

loss of privacy.
 Personality and Response to Illness 61

• Clinician response. The physician may feel ill at ease or question his or her
skills of communication and empathy because the patient seems difficult
to engage and conversations show no sign of establishing a connection.
The physician may suspect depression or conclude that the patient’s desire
to preserve a “circle of distance” reflects indifference toward the medical
problem; however, either interpretation is likely wrong. The challenge for
the physician is to respect the patient’s stance of “unsociability” while
maintaining a gentle, quiet interest in the patient that accepts the absence
of any reciprocal effort. Beneath the unemotional, seemingly imperturb-
able exterior, these patients may have a history of repeated disappoint-
ments in early life that taught them to regard the love of others as fickle
and untrustworthy. The physician, then, should try to honor the patient’s
preference for privacy, but not to the extremity of allowing the patient to
withdraw completely.

Impulsive, Acting-Out Patients

Impulsive, acting-out patients are intolerant of frustration, acute distress,
pain, and the necessity of either sustained collaboration or delayed gratifica-
tion. Sometimes even minor discomfort, delay, or frustration will leave the pa-
tient feeling overwhelmed by unbearable impotence. The patient will demand
immediate relief but rail against attempted intervention if it involves further
time or a procedure. The patient may curse, kick an IV pole, or demand to
sign out against medical advice. Such a patient seems devoid of the capacity to
deliberate; the patient may reach decisions immediately and later express re-
morse and explain that he or she acted “without thinking.”

• Perceived threat. The patient fears loss of comfort and consequent disinte-
gration.
• Clinician response. The physician may react to this patient with reflexive
dislike, concluding that the patient is choosing to throw a childish temper
tantrum that warrants forceful, adult discipline. By viewing the behavior as
possibly reflecting a defect in executive brain function, the physician will
find greater tolerance for the patient, and thereby more emotional “elbow
room” to select constructive interventions. Judicious but proactive use of
anxiolytic and analgesic medications may avert untimely and disruptive
62 Clinical Manual of Psychosomatic Medicine

eruptions of anger that often only delay treatment. Firm, but not punitive,
limit setting may actually reassure such patients that they will not be al-
lowed to utterly “fall to pieces.” The physician might recruit the presence of
family or a trusted friend to shore up the patient’s sense of safety.

Idealizing, Provocative Patients

Idealizing, provocative patients often seek to secure their self-esteem and yearning
for stability by searching for relationships that shower them with attention and
apparent singular commitment. The urgent longing to feel valued in relation-
ships, coupled with an amplified capacity to misinterpret, sets the stage for in-
tense, idealized perceptions. However, the inverse is also true: any disappointment
or perception of slight can unleash devastating doubt and explosive rage. Feeling
massively violated, such patients may be convinced that yesterday’s uniquely com-
passionate hero is today’s persecutory monster. Tumult spreads like contagion.

• Perceived threat. The patient fears that attachment, although desperately

desired, may prove all-consuming.
• Clinician response. The physician may initially endeavor to go the extra mile
in response to the patient’s provocative style and lament that he or she was
misunderstood by a prior insensitive and hurried physician, who, the pa-
tient may imply, simply did not display the attentive sagacity so clearly
present now. The physician may warm to the patient’s generous praise and
unwittingly allow overly optimistic expectations to blossom in the patient’s
imagined construction of a special connection. Disappointment is assured,
may be triggered by imperceptible snubs, and will lead to distracting up-
heaval. The physician may avoid disruptive commotion by conducting
himself or herself with consistent, caring clarity regarding necessary limits
and boundaries and by ensuring that the team communicates with a united
voice to the patient.

Cold, Deceitful Patients

Cold, deceitful patients may arouse suspicion and distaste from the outset, or
may assume a calculated charm that hides their true personality until they
have achieved their objective. These individuals have no regard for accepted
rules of fair play and consider the clinical encounter as one more relationship,
 Personality and Response to Illness 63

however brief, to exploit for social, legal, financial, or medicinal benefit. Some
of these patients may be confirmed criminals, and a few are dangerous. Un-
principled and sometimes devoid of conscience, such a patient may threaten
violence to self or hint at violence to another when he or she thinks it will bend
the physician to favorable action.

• Perceived threat. The patient believes that every relationship is a prelude to

betrayal, whether accomplished by foil or seduction.
• Clinician response. The physician may overlook early clues to the source
of the patient’s inappropriate demands, unconsciously preferring to avoid
confrontation. Most physicians resist being used and, even more so,
abused. When the antisocial patient’s effort to exploit becomes apparent,
the physician may be tempted to retaliate; however, even a liar who has
exaggerated his or her symptoms for personal gain may have an illness
that warrants medical attention. Physicians must stow their anger or dis-
gust, which may otherwise contaminate their medical reasoning. Special
requests from the patient (e.g., for a letter to court or a particular pre-
scription) are best answered in a straightforward, calm and firm manner
that relies on observation of fact and medical judgment, and the physi-
cian should avoid showing personal antipathy for the impropriety of the
patient’s demand. Argument is never constructive. The physician should
respect his or her own fear, and if he or she feels uncomfortable, should
suspend the examination until safety can be ensured.

Timid, Apprehensive Patients

Timid, apprehensive patients may be prone to private self-critique and may feel
either undeserving or unworthy of pressing for medical attention. They may be
willing to downplay any symptoms in the hope of dodging or deferring knowl-
edge of a medical diagnosis that may provoke fresh anxiety and uncertainty.
Some of these patients may have a dysthymic propensity that inclines them to
doubt that help or hope could be in store; they may reason that any malady that
does not utterly incapacitate them is best borne silently. Such a perspective may
collude with the patient’s anxiety to protect himself or herself from further un-
comfortable contact with the medical profession and the risk of discovering ad-
ditional reasons for anxiety.
64 Clinical Manual of Psychosomatic Medicine

• Perceived threat. The patient fears confirmation of his or her unfit, mar-
ginal, and onerous status.
• Clinician response. The physician may allow time constraints to conspire
with the patient’s innately hesitant style and gloss over meek responses
without summoning the patience and deliberate effort to extract a full, co-
hesive history from the patient. Occasionally, such patients will provide
more detail, with less censorship, on a written questionnaire than in an in-
terview. The careful physician will guard against betraying impatience or
irritation, lest the patient feel confirmed in his or her misgivings and seek
an early exit from the examination. The physician must be alert to subtle
clues of minimization or underreporting of symptoms and may seek fam-
ily for collateral history.

Common Defenses in Medical Patients

Understanding a patient’s defenses is one way to identify his or her behavioral
tendencies during times of stress. The consulting psychiatrist must remember
that patients under the stress of hospitalization and severe illness use less “ma-
ture” defenses that are nevertheless adaptive for the patients. Even if the de-
fenses cause problems for the patient care unit or clinic, these defenses are the
patient’s best available coping tools and, unless dangerous, should initially be
supported. Attempts to remove psychological defenses are almost always coun-
terproductive. A frontal assault on a patient’s less mature defenses usually
makes matters worse, causing intense fear, despair, anger, or even psychosis. If
the consulting psychiatrist’s interventions can reduce anxiety and discomfort,
the patient should be able to return to more characteristic, hopefully mature,
defenses. A patient’s defensive style may stir powerful feelings among the med-
ical team; these feelings may prompt the consultation request and may provide
important diagnostic information for the consulting psychiatrist. The follow-
ing are a sampling of mature, neurotic, and immature defenses that may be en-
countered in medical patients (Groves and Muskin 2011; Vaillant 1971).

Mature Defenses
• Anticipation—arranging whatever details are open to control to maximize
the odds of coping effectively
 Personality and Response to Illness 65

• Humor—giving open voice to “unacceptable feelings” by diluting the in-

tensity with irony, self-deprecation, or a surprising punch line
• Suppression—conscious distraction from ruminating about a coming diag-
nostic procedure

Neurotic Defenses

• Displacement—changing subjects when asked to talk about the illness or

injury
• Isolation of affect—discussing a diagnosis or serious prognosis devoid of
any expression of anxiety, fear, or dysphoria
• Rationalization—constructing a plausible, but typically untrue (in this in-
stance), reason for being untroubled by medical issues at hand
• Repression—unintentional, unconscious forgetting of a frightening, pain-
ful, or threatening experience or reaction

Immature Defenses

• Denial—steadfastly refusing to recognize threatening medical realities

• Passive aggression—“forgetting” to follow instructions (e.g., for urine col-
lection or for avoiding food or liquid intake), thus indirectly expressing
anger and thwarting a caregiver’s efforts
• Projection—ascribing intolerable motives, thoughts, or impulses to the
medical team
• Splitting—resorting to categorization of some caregivers as “all good” and
others as “all bad” to manage conflicting feelings

Helping the Patient Cope Constructively

Optimal management of maladaptive stress responses is not possible without
an understanding of how the patient sees himself or herself with this illness at
this time. Armed with this information, the consultant can recommend the
most appropriate psychopharmacological, psychotherapeutic, and unit man-
agement interventions. Therefore, after receiving a consult on a patient with
personality or coping style problems, the psychiatrist must do the following:
66 Clinical Manual of Psychosomatic Medicine

1. Identify and attempt to reverse any remediable organic factors.

2. Carefully consider whether other psychiatric disorders are present.
3. Clarify the patient’s style of personality functioning and past responses to
stressors.
4. Try to understand the meaning of the illness and hospitalization to the
patient.
5. Whenever possible, strive to engage the patient in ways that strengthen
resilience.
6. Recommend indicated somatic therapies, recognizing that in many con-
ditions, the foregoing steps may yield more immediate benefit than do
medications.

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sonality disorders, in The American Psychiatric Publishing Textbook of Consul-
tation-Liaison Psychiatry: Psychiatry in the Medically Ill, 2nd Edition. Edited by
Wise MG, Rundell JR. Washington, DC, American Psychiatric Publishing,
2002, pp 107–125
Vaillant GE: Theoretical hierarchy of adaptive ego mechanisms. Arch Gen Psychiatry
24:107–118, 1971
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 5
Suicidality

S uicidal statements made by medical-surgical patients usually lead to

prompt psychiatric referral. Inpatient consultation-liaison services work with
patients who have attempted suicide and been hospitalized in an intensive care
unit or general medical unit. Occasionally, even a hospitalized medical-surgi-
cal patient attempts or completes a suicide. Outpatient consultation services
work with patients whose medical conditions may be associated with thoughts
of suicide or of life as not worth living. Suicidality assessment is an integral
part of almost every psychosomatic medicine consultation.

Epidemiology
Completed Suicides
General Population

• Suicide is the eleventh leading cause of death in the United States and ac-
counts for over 33,000 documented deaths per year (Centers for Disease
Control and Prevention 2007).
• The most successful suicide method is firearms, followed by hanging and
self-poisoning (Juurlink et al. 2004).

69
70 Clinical Manual of Psychosomatic Medicine

• The elderly account for approximately 25% of suicides, although they ac-
count for only 10% of the population (Bostwick and Levenson 2005).
• Suicides among whites occur at twice the rate as nonwhites (excepting Na-
tive Americans) (Bostwick and Levenson 2005).
• The male-to-female ratio for suicide is 3:1 (Runeson and Asberg 2003).
Men tend to use more violent means, such as shooting, hanging, and
jumping from high places.
• Loss of a partner increases the risk for suicide (Bostwick and Levenson
2005). Divorced men have four times the suicide rate of married men, and
divorced women have three times the rate of married women.

Medical-Surgical Patients

• Physical disease is an independent suicide risk factor, present in 25%–

75% of people who commit suicide (Kontaxakis et al. 1988).
• Medical-surgical patients who commit suicide may have experienced a re-
cent loss of emotional support; anger may be a predominant affect.
• The reported suicide rate in most hospitals is lower than in the general
population. Access to means of suicide is more difficult in hospitals, and
patients who give clear warning signs are usually promptly attended to.
• Jumping is the most successful suicide method for general hospital pa-
tients (Bostwick and Levenson 2005).
• Most general hospital patients who commit suicide have chronic, painful,
or disfiguring illnesses (Sanders 1988). They also have a high frequency of
psychiatric illness, particularly mood disorders and alcohol use disorders.
Interpersonal problems with family members and ward staff are common.
• Institutional response is important. A suicide in a hospitalized patient can
be devastating. Successful organizational management of the aftermath of
an in-house suicide includes the formation of a multidisciplinary leader-
ship team (Ballard et al. 2008).

Attempted Suicides
General Population

• The ratio of suicide attempts to completions is about 10:1 (Bostwick and

Levenson 2005).
 Suicidality 71

• A 3:1 female-to-male ratio exists for suicide attempts, in contrast to the 3:1
male-to-female ratio for completed suicides (Bostwick and Levenson 2005).
• Suicide attempts are a common reason for admissions to general hospitals.
For example, 1%–2% of all admissions to emergency departments and
1%–5% of all admissions to medical intensive care units are drug overdose
patients (Bostwick and Levenson 2011).
• Drugs used in nonlethal suicide attempts are commonly available: benzo-
diazepines, alcohol, nonnarcotic analgesics, antidepressants, barbiturates,
and antihistamines. Overdoses of acetaminophen, with its potential liver
toxicity and over-the-counter availability, are particularly likely to result in
a medical-surgical or psychiatric admission.

Medical-Surgical Patients

• Although not well studied, the rate of attempted suicide in general hospital
settings is estimated at 24 per 100,000 patients per year (Sanders 1988).
• The most frequent psychiatric diagnosis in attempters is personality dis-
order, in contrast to depression and alcoholism in patients on medical-
surgical services who complete suicide (Sanders 1988).
• A recent history of loss of emotional support is common.
• Wrist slashing and drug overdose are the most common nonlethal suicide
attempt methods in hospitals (Sanders 1988).

Clinical Assessment
Psychiatric Risk Factors Associated
With Increased Suicide Risk
Psychiatric Diagnoses
Based on psychological autopsies, 95% of patients who completed suicides
had psychiatric diagnoses. Of these individuals, 40% had mood disorders,
20%–25% had alcoholism, 10%–15% had schizophrenia, and 20%–25%
had personality disorder (Litman 1989).
Past Attempts
History of a suicide attempt is an important predictor of future suicide risk.
One of every 100 suicide attempt survivors will die by suicide within 1 year af-
72 Clinical Manual of Psychosomatic Medicine

ter the index attempt, a suicide risk approximately 100 times that of the gen-
eral population (Hawton 1992).

Psychological Factors
Suicide is often a response to a loss, real or metaphorical. Fantasies of revenge,
punishment, reconciliation with a rejecting object, relief from the pain of loss,
or reunion with a dead loved one may be evident (Furst and Ostow 1979).
Holidays and anniversaries of important days also increase suicide risk.

Medical Disorders Associated With Increased Suicide Risk

Terminal Illness
Reviews of death certificates indicate that about 5% of suicide completers
have a terminal illness (Murphy 1986); however, this rate may underrepresent
the true prevalence. Physicians may misstate causes of death on death certifi-
cates to help patients’ families avoid adverse financial and psychosocial con-
sequences.

Medical Disorders With Specific Risk

Suicide rates higher than those in the general population are reported in pa-
tients with congestive heart failure, chronic obstructive pulmonary disease,
urinary incontinence, chronic pain, Alzheimer’s disease, diabetes, cancer, and
HIV, as well as in patients undergoing renal dialysis (Bostwick and Levenson
2011; Juurlink et al. 2004; Polednak 2007; Pompili et al. 2009; Voaklander et
al. 2008). The fear of pain, disfigurement, and loss of function from cancer,
HIV, and chronic renal failure can precipitate suicide, particularly early in the
patient’s course.

Treatment and Management

Identify the Risk Level
Initial management decisions may be difficult because patients are often am-
bivalent about suicide. In outpatient medical-surgical screening for suicidal-
ity, many times more patients may meet organizational criteria for mental
health referral for further suicidality assessment than are actually suicidal
(Shemesh et al. 2009). Patients demonstrate a gradation of risk. Most patients
 Suicidality 73

examined are at “some risk.” Information from a third party often helps the
clinician gain other perspectives on a patient’s situation. The clinician should
always err on the side of safety. The response of both patient and third party to
the treatment plan gives some indication of the patient’s resilience and of the
social resources available to aid in recovery from the suicidal crisis.

Protect the Patient

Arrange for Psychiatric Hospitalization
If the patient’s suicide potential is substantial, he or she should be hospitalized,
voluntarily or involuntarily.

Secure the Surroundings

If the patient requires medical hospitalization, once he or she is admitted to
the hospital, the patient’s room should be secured (Bostwick and Levenson
2011). The staff must do the following:

1. Remove dangerous articles (i.e., anything that a patient could potentially

use for self-injury, such as sharp objects or material that could be fash-
ioned into a noose). Access to means of suicide is associated with likeli-
hood of successful suicide completion in an impulsive in-hospital attempt
(Bostwick and Rackley 2007).
2. Search luggage and possessions.
3. Monitor all objects coming into the room that are potential weapons (e.g.,
the cutlery on the dinner tray).
4. Assertively address agitation. Agitation and anger are two emotional states
associated with likelihood of successful suicide completion in an impul-
sive in-hospital attempt (Bostwick and Rackley 2007).
5. Provide constant observation (e.g., by using a sitter).

Establish Capacity When Patients Reject

Life-Prolonging Treatments
A patient may decline life-prolonging treatments that complicate the natural
course of death and dying. This may sometimes be seen as a suicidal act. The
consulting psychiatrist should establish capacity for decision making in the
context of a suicidality assessment. Reality testing and rationality of explana-
74 Clinical Manual of Psychosomatic Medicine

tion for a decision to avoid life-prolonging treatments or technology are com-

ponent parts of this multiaxial assessment (Bostwick and Cohen 2009;
Sullivan and Youngner 1994).

Document Communications
The psychiatric consultant must carefully document the clinical diagnosis and
treatment plan in the patient’s chart. Frequent updates and reassessments of sui-
cide potential and the treatment plan are necessary. The consultant’s chart notes
should identify the level of risk, clearly state the plan, and report the interval at
which the consultant will return to continue the assessment and recommend
modifications to the plan (Bostwick and Levenson 2011). The consultant
should also arrange follow-up care for the patient before discharge and detail
this care in the chart so that it is part of the inpatient’s discharge plan.

Remove Risk Factors

Treat Psychiatric Disorders

• Mood disorders. Depressed patients receiving treatment should be ob-

served for a period of increased suicide risk during early phases of treat-
ment.
• Substance-related disorders. Alcohol and drug abuse is underdiagnosed
among medically ill patients, including patients in the general hospital.
• Psychosis. The consulting psychiatrist should ask about command halluci-
nations and treat psychotic symptoms.
• Delirium. Any remediable causes of cognitive impairment must be re-
moved.

Provide Medical Psychotherapy

Brief psychotherapy may be quite helpful for some suicidal patients, especially
when dealing with themes of loss. The psychiatrist or psychotherapist should
approach such patients with an accepting, supportive, empathic, and con-
cerned manner and attempt to develop a therapeutic alliance. The patient’s
family should be involved, whenever possible. The clinician should make an
effort to reestablish or strengthen the patient’s connections to friends or com-
munity social service agencies.
 Suicidality 75

Manage Patient in Emergency Department and Outpatient Setting

According to Davidson (1993), the emergency department or outpatient
clinic setting is acceptable for outpatient management if the suicidal patient
has the following:

• Satisfactory impulse control

• No psychosis or intoxication
• No specific plan or easily accessible means for suicide
• Accessible social supports to which he or she is willing to turn
• The capacity for establishing rapport with the consultant

References
Ballard ED, Pao M, Horowitz L, et al: Aftermath of suicide in the hospital: institu-
tional response. Psychosomatics 49:461–469, 2008
Bostwick JM, Cohen LM: Differentiating suicide from life-ending acts and end-of-life
decisions: a model based on chronic kidney disease and dialysis. Psychosomatics
50:1–7, 2009
Bostwick JM, Levenson JL: Suicidality, in The American Psychiatric Publishing Text-
book of Psychosomatic Medicine. Edited by Levenson JL. Washington, DC,
American Psychiatric Publishing, 2005, pp 219–234
Bostwick JM, Levenson JL: Suicidality, in The American Psychiatric Publishing Text-
book of Psychosomatic Medicine, 2nd Edition. Edited by Levenson JL. Wash-
ington, DC, American Psychiatric Publishing, 2011, pp 199–218
Bostwick JM, Rackley SJ: Completed suicide in medical/surgical patients: who is at
risk? Current Psychiatry Reports 9:242–246, 2007
Centers for Disease Control and Prevention: 20 leading causes of death, United States,
2007. WISQARS Leading Causes of Death Reports, 1999–2007. Office of Sta-
tistics and Programming, National Center for Injury Prevention and Control.
Data Source: National Center for Health Statistics (NCHS), National Vital Sta-
tistics System. 2007. Available at: http://webappa.cdc.gov/sasweb/ncipc/
leadcaus10.html. Accessed April 6, 2011.
Davidson L: Suicide and aggression in the medical setting, in Psychiatric Care of the
Medical Patient. Edited by Stoudemire A, Fogel BS. New York, Oxford Univer-
sity Press, 1993, pp 71–86
76 Clinical Manual of Psychosomatic Medicine

Furst S, Ostow M: The psychodynamics of suicide, in Suicide: Theory and Clinical As-
pects. Edited by Hankoff LD, Einsidler B. Littleton, MA, PSG Publishing, 1979,
pp 165–178
Hawton K: Suicide and attempted suicide, in Handbook of Affective Disorders, 2nd
Edition. Edited by Paykel ES. New York, Guilford, 1992, pp 635–650
Juurlink DN, Nerrman N, Szalai JP, et al: Medical illness and the risk of suicide in the
elderly. Arch Intern Med 164:1179–1184, 2004
Kontaxakis VP, Christodoulou GN, Mavreas VG, et al: Attempted suicide in psychiatric
outpatients with concurrent physical illness. Psychother Psychosom 50:201–206,
1988
Litman RE: Suicides: what do they have in mind? in Suicide: Understanding and Re-
sponding. Edited by Jacobs D, Brown HN. Madison, CT, International Univer-
sities Press, 1989, pp 143–154
Murphy GE: Suicide and attempted suicide, in The Medical Basis of Psychiatry. Edited
by Winokur G, Clayton PJ. Philadelphia, PA, WB Saunders, 1986, pp 562–579
Polednak AP: Suicide among breast cancer patients who have had reconstructive sur-
gery: a population-based study. Psychosomatics 48:178–179, 2007
Pompili M, Lester D, Innamorati M, et al: Quality of life and suicide risk in patients
with diabetes mellitus. Psychosomatics 50:16–23, 2009
Runeson B, Asberg M: Family history of suicide among suicide victims. Am J Psychi-
atry 160:1525–1526, 2003
Sanders R: Suicidal behavior in critical care medicine: conceptual issues and manage-
ment strategies, in Problems in Critical Care Medicine. Edited by Wise MG.
Philadelphia, PA, JB Lippincott, 1988, pp 116–133
Shemesh E, Annunziato RA, Rubinstein D, et al: Screening for depression and suicid-
ality in patients with cardiovascular illnesses. Am J Cardiol 104:1194–1197,
2009
Sullivan MD, Youngner SJ: Depression, competence, and the right to refuse lifesaving
medical treatment. Am J Psychiatry 151:971–978, 1994
Voaklander DC, Rowe BH, Dryden DM, et al: Medical illness, medication use and
suicide in seniors: a population-based case control study. J Epidemiol Commu-
nity Health 62:138–146, 2008
PA R T I I

Syndromes
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 6
Anxiety

Anxiety in medically ill patients has various causes. Anxiety can be a reac-
tion to the stress of illness or hospitalization, a manifestation of a medical or
psychiatric disorder, a result of substance abuse or withdrawal, or an adverse
effect of a medication (Miller and Massie 2006).
Anxiety is associated with medical morbidity. The impact of anxiety dis-
orders on function and outcome in persons with chronic medical illness is not
as well studied as the impact of depression. Available evidence, however, sug-
gests that anxiety may have as great an impact as depression in terms of risk,
outcomes, and measures of morbidity (Roy-Byrne et al. 2008). Kessler et al.
(2003) reported that anxiety disorders had an association equal to or greater
than that of depression with four chronic medical conditions: hypertension,
arthritis, asthma, and ulcers. Anxiety often amplifies somatic symptoms (e.g.,
tachycardia, dyspnea, pain) and worsens outcomes (Roy-Byrne et al. 2008).
Anxiety is associated with health care utilization. Anxiety accounts for up
to 10% of all visits to physicians (Colon and Popkin 2002). Anxiety symptoms
are easily mistaken for cardiac arrhythmia, asthma, cerebrovascular disease,
coronary disease, an endocrine disorder, or vertigo. Consequently, patients

79
80 Clinical Manual of Psychosomatic Medicine

with anxiety disorders are frequently referred for expensive and unnecessary ex-
aminations, such as ambulatory electrocardiographic monitoring, cardiac cath-
eterization, and pheochromocytoma testing (Simon and Walker 1999). Anxi-
ety severity also correlates with frequency of health care use, health care cost,
and length of hospital stay, even when accounting for illness severity (Colon
and Popkin 2002; Epstein and Hicks 2011; Levenson et al. 1992; Saravay et al.
1991).

Epidemiology
General Population
Anxiety disorders are among the most common psychiatric disorders. The
lifetime prevalence of anxiety disorders is 25%; the 12-month prevalence is
17% (Colon and Popkin 2002; Epstein and Hicks 2011). Compared with
men, women are at twice the risk for having a current anxiety disorder.

Medically Ill Patients

Patients with chronic medical conditions have a 50% higher lifetime preva-
lence of an anxiety disorder (Wells et al. 1988). Panic disorder is present in 3–
10 times more patients with asthma than in the general population (Colon and
Popkin 2002). When panic disorder is treated in medical patients, hospitaliza-
tion rates decline (Katon 1984).

Biology of Anxiety
Neurotransmitters
Basic science and clinical research implicate noradrenergic, serotonergic, and
γ-aminobutyric acid (GABA) systems, and possibly glucocorticoid neuropep-
tides, in the genesis of normal and pathological anxiety.

Neurophysiology
Patients with anxiety disorders appear to have unstable autonomic nervous sys-
tems, hypersensitive respiratory control mechanisms, and hypersensitive cen-
tral nervous system (CNS) carbon dioxide (CO2) chemoreceptors (Colon and
Popkin 2002).
 Anxiety 81

Neuroanatomy
Pharmacological challenge studies and functional CNS imaging suggest that
key CNS structures that are important in producing normal and pathological
anxiety include the locus coeruleus, amygdala, hippocampus, temporal lobes,
and frontal lobes. Projections from the amygdala and hypothalamus modulate
autonomic and endocrine responses associated with regulation of vigilance
and anxiety; amygdala stimulation in humans induces anxiety and fear (Colon
and Popkin 2002).

Anxiety Disorders
Secondary Anxiety (Toxic or Metabolic Etiologies)
Anxiety Secondary to General Medical Condition
Anxiety due to a general medical condition exists when a patient has patholog-
ical anxiety that is an integral part of the pathophysiology of a medical illness or
metabolic syndrome (e.g., anxiety caused by a hyperthyroid state). Sometimes,
the diagnosis is finalized only after the fact, when removing the medical etiol-
ogy remediates the anxiety or panic symptoms. Even then, relations between
organic and reactive aspects of an overall anxiety syndrome are complex; having
a medical condition causally related to a secondary anxiety syndrome does not
rule out reactive anxiety.

Anxiety Induced by Substance

Substance-induced anxiety disorder is diagnosed when the anxiety symptoms
are linked to substance intoxication or withdrawal. The symptoms must emerge
within a month of substance intoxication or withdrawal.

Causes of Secondary Anxiety

Causes of secondary anxiety are numerous, as demonstrated in the following
list. (Examples are given for each category.)

• Cardiovascular conditions (e.g., angina, cardiac dysrhythmia, cerebrovas-

cular insufficiency, congestive heart failure, hypovolemia, left ventricular
assist device, myocardial infarction, syncope, paroxysmal atrial tachycar-
dia, valvular disease)
82 Clinical Manual of Psychosomatic Medicine

• Metabolic conditions (e.g., anemia, hyperkalemia, hyperthermia, hypona-

tremia)
• Endocrine conditions (e.g., carcinoid syndrome, hyperadrenalism, hyper-
thyroidism, hypocalcemia, hypoparathyroidism, pheochromocytoma)
• Neurological conditions (e.g., encephalitis, postencephalitic syndromes,
Huntington’s disease, multiple sclerosis, neurosyphilis, restless legs syn-
drome, seizure disorder [especially temporal lobe epilepsy], stroke, vascu-
lar headaches)
• Respiratory conditions (e.g., asthma, chronic obstructive pulmonary dis-
ease, pneumonia, pneumothorax, pulmonary edema, pulmonary embo-
lus, ventilator dependence)
• Drugs and withdrawal (e.g., alcohol and its withdrawal, aminophylline/
theophylline, amphetamine, anticholinergics, antidepressants, caffeine,
calcium channel blockers, cannabis, cocaine, digitalis toxicity, ephedrine,
epinephrine, hallucinogens, insulin, levodopa, lidocaine, methylpheni-
date, antipsychotics (akathisia), phenylephrine, procaine, procarbazine,
pseudoephedrine, salicylates, sedative-hypnotic withdrawal, steroids, sym-
pathomimetics, thyroid preparations, yohimbine)

Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is characterized by excessive anxiety plus
apprehensive expectations about events or activities. A patient’s incessant worry
is difficult to control and commonly evokes restlessness, fatigue, irritability,
muscle tension, and sleep dysfunction (American Psychiatric Association 2000).
When encountered in psychosomatic medicine, GAD is often an established
condition that is exacerbated or unmasked in the outpatient or inpatient med-
ical-surgical setting. Patients with GAD often have other psychiatric disorders.
Motor tension, which may include trembling and twitching, is a routine part of
GAD. Age at onset is usually the 20s or 30s.

Panic Disorder
Patients with primary panic disorder have recurrent, unexpected panic at-
tacks, followed by worry, concern, and behavior changes related to the attacks
(American Psychiatric Association 2000). The attacks are not due to a general
medical condition or the direct effects of a substance. Panic disorder is under-
 Anxiety 83

recognized, underdiagnosed, and undertreated in outpatient medical settings.

Panic disorder was present in about 35%–45% of the patients with chest pain
whose cardiac catheterizations indicated normal coronary arteries (Colon and
Popkin 2002).

Agoraphobia Without Panic Disorder

Patients with agoraphobia are not seen in medical-surgical settings for the
simple reason that they rarely leave home unless there is a life-threatening
emergency or unless their family or an outreach program brings them to med-
ical attention.

Specific Phobias and Social Anxiety Disorder

Specific phobias and social anxiety disorder are usually hidden by the patient
and are seldom identified by the primary care physician (Colon and Popkin
2002), unless the degree of impairment is pronounced or interferes with clin-
ical care, such as when a claustrophobic patient cannot tolerate the magnetic
resonance imaging procedure or when phobias involve blood, injection, gen-
eral anesthesia, or injury. Patients often delay seeking medical attention be-
cause of avoidance associated with specific phobias.

Obsessive-Compulsive Disorder
Ego-dystonic obsessions and irresistible compulsive behaviors can produce so-
matic manifestations. For example, patients can develop dermatoses from fre-
quent washing, and scarring from scratching. Obsessive-compulsive disorder
(OCD) is highly comorbid with major depressive disorder and other anxiety
disorders. Primary OCD, when it appears or recurs during a hospitalization or
an outpatient workup for a new medical problem, may be aggravated by the
stress, uncertainty, and loss of control experienced by patients. Secondary ob-
sessive-compulsive syndromes occur in several neuropsychiatric conditions,
including Tourette syndrome and epilepsy, and after head injury.

Acute Stress Disorder

Acute stress disorder (ASD) involves exposure to a life-threatening event that
produces dissociative symptoms, reexperiencing of the trauma, avoidance of as-
sociated stimuli, increased arousal, and significant distress or social or occupa-
84 Clinical Manual of Psychosomatic Medicine

tional impairment (American Psychiatric Association 2000). Symptoms must

last for more than 2 days but no more than 4 weeks and emerge within 1 month
of the trauma. The symptoms are not substance induced and do not result from
metabolic aspects of a general medical condition, although a life-threatening
medical condition can certainly be the stressor associated with the psychological
symptoms. ASD identifies patients at risk for posttraumatic stress disorder
(PTSD); 50% of individuals with ASD go on to develop PTSD.

Posttraumatic Stress Disorder

A diagnosis of PTSD requires that a life-threatening trauma is persistently re-
experienced, that the duration of the symptoms is longer than 1 month, that
emotional numbing and increased arousal are present, and that stimuli linked
to the trauma are avoided (American Psychiatric Association 2000). The expe-
rience of hospitalization or severe illness can trigger reexperiencing phenomena,
nightmares, strong emotions, and autonomic arousal. A PTSD diagnosis
should alert the clinician to the potential presence of comorbid psychiatric dis-
orders, especially substance-related disorders, mood disorders, and panic disor-
der. PTSD risk is elevated when a person has traumatic brain injury. Traumatic
stress disorders and their treatment are discussed in more detail in Chapter 19,
“Disaster and Terrorism Casualties.”

Adjustment Disorder With Anxiety

Adjustment disorder is a maladaptive response to an identifiable stressor. For
many patients, the stressors are the medical illness, the clinic or hospital en-
vironment, and the treatment. Common sources of anxiety include uncer-
tainty regarding medical diagnosis or prognosis; fears of amputation, loss of
functional capacities, dependency, pain, or death; the potential impact of ill-
ness on the ability to work, perform essential household functions, or main-
tain income; and discomfort in the hospital due to being alone or entrusting
one’s care to strangers.

Health Anxiety
Definition
Health anxiety is worry or fear about having or getting a serious disease. There
is a substantial focus on somatic symptoms, checking for signs of physical ill-
ness, and efforts to get reassurance from loved ones and the health care system.
 Anxiety 85

Prevalence
In the U.S. general population, 3%–10% of individuals have significant
health anxiety (Abramowitz and Braddock 2008); up to 30% of the popula-
tion experience intermittent or milder fears about health.

Causes
The etiology of pathological health anxiety may be multifactorial in an indi-
vidual patient. Causes may include genetically anxious temperament, early
negative childhood experiences, social learning and modeling, and previously
stressful experiences with illness and death (Abramowitz and Braddock 2008).

Differential Diagnosis
When pathological anxiety is present, the symptoms may be due to situational
stress, a primary anxiety disorder, or a medical or toxic etiology. Several im-
portant questions must be answered when differentiating among causes of
pathological anxiety:

1. What past and family historical data are present? Past or family history of a
primary anxiety disorder increases the probability that current signs and
symptoms are manifestations or recurrences of a primary anxiety disorder.
2. Is there an identifiable potential medical or toxic cause for the anxiety? The
differential diagnosis of anxiety disorders includes a wide range of physical
illnesses and psychoactive substances. Evaluation directed toward the body
system most prominently affected by anxiety symptoms (e.g., gastrointes-
tinal, respiratory) may provide diagnostic evidence for the etiology.
3. What other potential psychiatric disorders are present? Anxiety disorders are
sometimes mistaken for other psychiatric disorders, especially agitated
depression. Anxiety disorders usually have an earlier age at onset and are
less episodic than mood disorders. Anxiety disorders frequently coexist
with other psychiatric disorders, especially depression and substance-
related disorders.
4. What does the mental status examination show? The mental status exami-
nation differentiates agitated delirium and psychotic disorders from anx-
iety disorders. The akathisia that occasionally occurs with antipsychotics
can resemble anxiety.
86 Clinical Manual of Psychosomatic Medicine

Treatment and Management

Anxiety Disorder Due to General Medical Condition
or Substance
When a remediable etiology for an anxiety syndrome is found, the clinician
should reverse it, unless medically impossible or contraindicated. Unless anx-
iety symptoms are self-limited, treatment is indicated.

Acute Anxiety and Generalized Anxiety Disorder

Benzodiazepines
Benzodiazepines are effective anxiolytics. Few features make them potentially
dangerous, especially with short-term use, in medically ill hospitalized patients.
However, tolerance, dependence, and accident proneness present limitations to
long-term use of benzodiazepines for some patients in the ambulatory setting.
In patients without a history of previous addiction or risk factors for it, iatro-
genic addiction is seldom a concern. Table 6–1 summarizes clinical and phar-
macodynamic information about the most commonly used benzodiazepines.
Dosages for elderly and medically ill patients should start lower than those for
physically healthy younger patients.
Importance of half-life. Agents with longer half-lives (e.g., diazepam, clo-
nazepam) can be administered less frequently and may be easier to taper after
prolonged use than agents with shorter half-lives. However, the former are
more likely to accumulate in patients who have impaired hepatic function or
who are taking multiple medications. Agents with shorter half-lives reach
steady state much more rapidly and are eliminated more quickly, making
them reasonable options for the short-term management of anxiety.
Lorazepam and oxazepam. Lorazepam and oxazepam are metabolized by
glucuronidation, have no active metabolites, and are better suited for patients
with liver impairment or patients taking multiple medications.
Alternate routes of administration. Among benzodiazepines, only loraz-
epam and midazolam are reliably absorbed when administered intramuscu-
larly. Lorazepam, midazolam, and diazepam can be given intravenously, and
lorazepam can be absorbed sublingually.
 Anxiety 87

Adverse effects. The most common side effect of benzodiazepines is seda-

tion. Dizziness, weakness, anterograde amnesia (correlated with decreasing du-
ration of action), nausea, and impaired motor performance are also reported.
Tolerance can develop with chronic use. Withdrawal syndromes occur if dos-
age is reduced rapidly.

Buspirone
Advantages in medically ill patients. Buspirone has advantages in medi-
cally ill patients because it is not sedating, has few drug interactions, and has
no known abuse potential. Buspirone may be a particularly desirable choice in
treating chronic anxiety in patients with severe chronic lung disease because it
does not cause respiratory depression (Garner and Eldridge 1989).
Efficacy. Evidence indicates that buspirone may be effective for GAD for
some patients. Buspirone is not useful in the treatment of acute anxiety be-
cause its onset of therapeutic response requires 2–4 weeks or possibly longer.
Buspirone is not effective as a primary treatment for panic disorder.
Dosage. The average total daily dosage of buspirone is 30 mg, but the initial
dosage is 5 mg twice daily, which can be increased by 5 mg/day every 3–4
days.
Adverse effects. The adverse effects of buspirone include nausea, vomiting,
headache, and dizziness. Buspirone can produce serotonin syndrome when
taken with monoamine oxidase inhibitors (MAOIs) or with other medica-
tions that increase serotonin activity (Fait et al. 2002). It also can displace less
firmly protein-bound drugs such as digoxin.

Antidepressants
Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and
serotonin-norepinephrine reuptake inhibitors (SNRIs), are effective in the
treatment of GAD and other anxiety disorders (Gorman and Kent 1999).
Most patients obtain some benefit within 2 weeks, with additional improve-
ment over the next 6–8 weeks of treatment (Schatzberg 2003). Duloxetine,
citalopram, paroxetine, sertraline, and venlafaxine have been approved by the
U.S. Food and Drug Administration (FDA) for treatment of GAD.
Table 6–1. Benzodiazepines in medical-surgical patients

88 Clinical Manual of Psychosomatic Medicine

Usual therapeutic Approximately Approximately
Duration of dosage range equivalent anxiolytic equivalent hypnotic
Generic name Trade name Onset action (mg/day)a dosage (mg) dosage (mg)

Alprazolam Xanax Intermediate Short 2–8 0.5 1

Chlordiazepoxide Librium Intermediate Long 15–150 10 25
Clonazepam Klonopin Intermediate Long 1–3 1 1
Clorazepate Tranxene Rapid Long 15–60 7.5 15
Diazepam Valium Rapid Long 5–40 5 10
Estazolam ProSom Rapid Intermediate 1–2 — 1
Flurazepam Dalmane Rapid to Long 15–30 — 30
intermediate
Lorazepam Ativan Intermediate Intermediate 1–6 1 2
Midazolam Versed Rapid Very short 0.1 mg/kg 2 2
Oxazepam Serax Intermediate to Intermediate 30–120 15 30
slow
Prazepam Centrax Slow Long 20–60 10 20
Quazepam Doral Rapid Long 7.5–15 — 15
Table 6–1. Benzodiazepines in medical-surgical patients (continued)
Usual therapeutic Approximately Approximately
Duration of dosage range equivalent anxiolytic equivalent hypnotic
Generic name Trade name Onset action (mg/day)a dosage (mg) dosage (mg)

Temazepam Restoril Intermediate to Short 15–30 15 30

slow
Triazolam Halcion Intermediate Short 0.125–0.5 — 0.5
aDoses for elderly and medically ill patients are often lower.
Source. Adapted from Fait ML, Wise MG, Jachna JS, et al.: “Psychopharmacology,” in The American Psychiatric Publishing Textbook of Consultation-
Liaison Psychiatry: Psychiatry in the Medically Ill, 2nd Edition. Edited by Wise MG, Rundell JR. Washington, DC, American Psychiatric Publishing, 2002,
pp. 939–987. Copyright, American Psychiatric Publishing, Inc. Used with permission.

Anxiety
89
90 Clinical Manual of Psychosomatic Medicine

Antipsychotic Medications
Antipsychotics may be beneficial in the medical setting when anxiety is accom-
panied by extreme fear, agitation, or delirium, although this is an off-label use.
For example, 0.5 mg of haloperidol two or three times per day can markedly re-
duce the extreme fear that patients sometimes experience when they are being
weaned from a ventilator. Low-dose antipsychotics can be useful in treating
secondary anxiety disorders and other secondary psychiatric disorders resulting
from high-dose steroids. Patients who are medically ill and have severe, refrac-
tory anxiety or panic or those in whom sedation from benzodiazepine agents
cannot be tolerated also may benefit from a cautious trial of antipsychotics.
The treating physician usually checks an electrocardiogram and observes the
patient for acute dystonia, akathisia, and signs of neuroleptic malignant syn-
drome.

Beta-Blockers
Beta-blockers help control some peripheral sympathetic nervous system
symptoms of anxiety, such as palpitations and sweating. The psychological
components of anxiety are not ameliorated. Adverse effects of beta-blockers
include bradycardia, hypotension, and fatigue.

Medical Psychotherapy
Supportive psychotherapy. Supportive psychotherapy can help patients
cope with acute stressors during a hospitalization or series of clinic visits.
Cognitive-behavioral therapy. Cognitive-behavioral therapy (CBT) has
demonstrated efficacy in treatment of anxiety disorders, including in medi-
cally ill patients (Kunik et al. 2008; Welkowitz et al. 1991). CBT involves ac-
tive exploration, clarification, and testing of the patient’s perceptions, beliefs,
and self-perpetuating pathological behavior patterns.
Psychodynamic psychotherapy. Common psychodynamic themes in pa-
tients with anxiety are loss, real and metaphorical physical threats, and lack of
control. The clinician needs to address potential factors in the hospital envi-
ronment that may be associated with the hospitalized patient’s anxiety. These
include intrusive medical procedures, sleep deprivation, financial stressors,
noise, loss of privacy, and medical uncertainty.
 Anxiety 91

Behavior therapies. Behavior therapies provide an opportunity for reduc-

tion of acute anxiety, enhancement of the patient’s sense of mastery, and clar-
ification of measurable goals. Behavioral interventions commonly used in psy-
chosomatic medicine include relaxation techniques, systematic exposure and
desensitization, biofeedback, meditation, hypnosis, and establishing graded
goals with simple reinforcement schedules.

Panic Disorder
Benzodiazepines
Alprazolam and clonazepam are approved by the FDA for treatment of panic
disorder; they may be most useful when rapid control of attacks is necessary. A
significant limitation of alprazolam in chronic treatment of panic is the poten-
tial for dependence, withdrawal, and rebound symptoms on discontinuation
and between doses. Discontinuation of alprazolam should be very gradual.
Clonazepam has a longer half-life than alprazolam (24–48 hours); it is quite se-
dating for many patients.
Antidepressants
Four antidepressants (fluoxetine, paroxetine, sertraline, and venlafaxine) have
received FDA approval for use in treating panic disorder. After a 2-week sin-
gle-blind placebo lead-in, 168 patients with panic disorder entered a 10-week
double-blind phase in which they were randomly assigned to treatment with
either sertraline or placebo. Compared with placebo-treated patients, patients
receiving the SSRI experienced decreases in frequency, severity, and duration
of panic attacks (Pohl et al. 1998). Antidepressant dosages used for panic are
similar to those used for depression, but higher dosages are frequently neces-
sary for complete control of panic attacks, including the elimination of lim-
ited-symptom panic attacks. Tricyclic antidepressants, trazodone, and MAOIs
are also efficacious, but panic disorder is an off-label usage. Bupropion is not
effective in treating panic disorder. Chapter 10, “Mood Disorders,” contains
information on normal antidepressant dosages and potential adverse effects.
Antipsychotic Medications
Antipsychotics can be effective for rapid relief of acute panic attacks that en-
danger life or medical status. Parenteral haloperidol, in dosages of 2–5 mg (or
higher if needed), can help control attacks, but this is an off-label use.
92 Clinical Manual of Psychosomatic Medicine

Other Medications
Propranolol blocks some peripheral manifestations of panic attacks. Cloni-
dine is effective in decreasing symptoms in some patients.

Medical Psychotherapy
Explaining panic disorder to the patient as a part of supportive psychotherapy
is helpful and reassuring. Behavioral, cognitive-behavioral, and relaxation ther-
apies are effective primary or adjunctive treatments for panic disorder (Kunik
et al. 2008). Cognitive-behavioral approaches emphasize the combination of
symptom control (especially breathing) and cognitive restructuring to give
physical symptoms a noncatastrophic interpretation. Use of medication and
psychotherapy together is particularly efficacious, especially for patients with
severe panic disorder.

Specific Phobia and Social Anxiety Disorder

The treatment of choice for specific phobia is graded exposure. In the hospi-
talized patient, exposure treatments do not have to be in vivo. Imagery-based
exposure that uses a graded hierarchy of anxiety-producing stimuli is also ef-
fective (Hollander et al. 1988). Social anxiety in the outpatient setting is ame-
nable to treatment with SSRIs and SNRIs. Paroxetine, sertraline, and the ex-
tended-release version of venlafaxine are approved by the FDA to treat social
anxiety disorder and are superior to placebo, although overall, fewer than half
of patients respond favorably (Stein et al. 1999).

Obsessive-Compulsive Disorder
Clomipramine is a potent serotonin reuptake blocker but is not well tolerated
because of side effects. Two-thirds of patients with OCD who take clomipra-
mine can expect significant symptomatic improvement; some patients have
almost complete remission (Hollander et al. 1988). SSRIs are also effective for
obsessive-compulsive symptoms, and they lack anticholinergic and sedating
side effects. Three SSRI antidepressants—fluoxetine, paroxetine, and sertra-
line—are approved by the FDA for treating OCD. OCD treatment is en-
hanced when medication is combined with behavioral treatments, such as
graded exposure and response prevention techniques.
 Anxiety 93

Acute Stress Disorder and Posttraumatic Stress Disorder

Patients may have experienced traumatic events that resulted in hospitaliza-
tion (e.g., motor vehicle accidents) or events that occurred in medical facilities
(e.g., cardiac arrests). The mainstay of treatment of ASD and PTSD is CBT-
based group and individual psychotherapy, along with antidepressant medi-
cation. Detailed discussion of the treatment of ASD and PTSD appears in
Chapter 19, “Disaster and Terrorism Casualties.”

Health Anxiety
Antidepressants and antianxiety medications may address some of the physi-
ological manifestations of health anxiety. The primary psychological treat-
ment shown to be effective for health anxiety is CBT. The goals of treatment
(Abramowitz and Braddock 2008) are to help the patient do the following:

1. Decrease specific behaviors, such as frequent checking of the body for

symptoms and asking for reassurance about health
2. Overcome avoidance of situations related to illness
3. Learn to face worries about illness realistically
4. Learn to reduce fear associated with thoughts about health and death
5. Accept the reality of ultimate death and resolve to enjoy life to its fullest
6. Improve relaxation and stress management skills
7. Improve physical conditioning

References
Abramowitz J, Braddock A: Treatment of Health Anxiety and Hypochondriasis: A
Biopsychosocial Approach. Ashland, OH, Hogrefe & Huber, 2008
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disor-
ders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Associ-
ation, 2000
Colon EA, Popkin MK: Anxiety and panic, in The American Psychiatric Publishing
Textbook of Consultation-Liaison Psychiatry: Psychiatry in the Medically Ill, 2nd
Edition. Edited by Wise MG, Rundell JR. Washington, DC, American Psychi-
atric Publishing, 2002, pp 393–415
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Epstein SA, Hicks D: Anxiety disorders, in The American Psychiatric Publishing Text-
book of Psychosomatic Medicine, 2nd Edition. Edited by Levenson JL. Wash-
ington DC, American Psychiatric Publishing, 2011, pp 241–260
Fait ML, Wise MG, Jachna JS, et al: Psychopharmacology, in The American Psychi-
atric Publishing Textbook of Consultation-Liaison Psychiatry: Psychiatry in the
Medically Ill, 2nd Edition. Edited by Wise MG, Rundell JR. Washington, DC,
American Psychiatric Publishing, 2002, pp 939–987
Garner SJ, Eldridge FL: Buspirone, an anxiolytic drug that stimulates respiration. Am
Rev Respir Dis 139:945–950, 1989
Gorman JM, Kent JM: SSRIs and SNRIs: broad spectrum of efficacy beyond major
depression. J Clin Psychiatry 60 (suppl 4):33–38, 1999
Hollander E, Liebowitz MR, Gorman JM: Anxiety disorders, in The American Psy-
chiatric Press Textbook of Psychiatry. Edited by Talbott JA, Hales RE, Yudofsky
SC. Washington, DC, American Psychiatric Press, 1988, pp 443–491
Katon W: Panic disorder and somatization: review of 55 cases. Am J Med 77:101–106,
1984
Kessler RC, Ormel J, Demler O, et al: Comorbid mental disorders account for the role
impairment of commonly occurring chronic physical disorders: results from the
National Comorbidity Survey. J Occup Environ Med 45:1257–1266, 2003
Kunik ME, Veazey C, Cully JA, et al: COPD education and cognitive behavioral ther-
apy group treatment for clinically significant symptoms of depression and anxiety
in COPD patients: a randomized controlled trial. Psychol Med 38:385–396,
2008
Levenson JL, Hamer RM, Rossiter LF: Psychopathology and pain in medical inpa-
tients predict resource use during hospitalization but not rehospitalization. J Psy-
chosom Res 36:585–592, 1992
Miller K, Massie MJ: Depression and anxiety. Cancer J 12:388–397, 2006
Pohl RB, Wolkow RM, Clary CM: Sertraline in the treatment of panic disorder: a dou-
ble-blind multicenter trial. Am J Psychiatry 155:1189–1195, 1998
Roy-Byrne PP, Davidson KW, Kessler RC, et al: Anxiety disorders and comorbid med-
ical illness. Focus 6:467–485, 2008
Saravay SM, Steinberg MD, Weinschel B, et al: Psychological comorbidity and length
of stay in the general hospital. Am J Psychiatry 148:324–329, 1991
Schatzberg A: Antidepressants, in Manual of Clinical Psychopharmacology, 4th Edi-
tion. Edited by Schatzberg AF, Cole JO, DeBattista C. Washington, DC, Amer-
ican Psychiatric Publishing, 2003, pp 37–157
Simon GE, Walker EA: The consultation psychiatrist in the primary care clinic, in Es-
sentials of Consultation-Liaison Psychiatry. Edited by Rundell JR, Wise MG.
Washington, DC, American Psychiatric Press, 1999, pp 513–520
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Stein MB, Fyer AJ, Davidson JRT, et al: Fluvoxamine treatment of social phobia (social
anxiety disorder): a double-blind, placebo-controlled study. Am J Psychiatry
156:756–760, 1999
Welkowitz LA, Papp LA, Cloitre M, et al: Cognitive-behavior therapy for panic dis-
order delivered by psychopharmacologically oriented clinicians. J Nerv Ment Dis
179:472–476, 1991
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lation with and without chronic medical conditions. Am J Psychiatry 145:976–
981, 1988
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 7
Delirium

Definition
Delirium is a global dysfunction in cerebral metabolism that generally has an
acute onset; is often reversible; may be persistent; and is associated with sig-
nificant mortality, morbidity, and health care cost.

Recognition
Delirium is underrecognized, even in settings where it is common. Palliative
care physicians and nurses identify patients with rating scale–confirmed de-
lirium only 44% of the time (Fong et al. 2009).

Consultation Effectiveness
Psychiatric consultation can improve outcomes for patients with delirium.
General hospital patients with delirium who receive psychiatric consultations,
compared with those who do not, have a lower readmission rate (33% vs.
50%, P=0.01) and lower likelihood of discharge to a nursing home (21% vs.
36%, P=0.02) (Mittal et al. 2006).

97
98 Clinical Manual of Psychosomatic Medicine

Epidemiology
Incidence
The prevalence of delirium is 1%–2% in the community but 15%–25%
among patients in the general hospital and 30%–80% among patients in the
intensive care unit (ICU) (Fong et al. 2009). Delirium incidence in the hos-
pital varies widely by setting. Prevalence and incidence are highest in complex
care settings, such as postoperative, intensive care, and palliative care settings
(Fong et al. 2009; Franco et al. 2001; Robinson et al. 2009; Siddiqi et al.
2006).

Mortality
Mortality in delirium patients is estimated to be 15%–30% in the hospital
and up to 40% over 1 year in elderly patients with delirium (Inouye 2006;
Tennen and Rundell 2008).

One-Year Mortality
The relative risk for mortality in elderly patients with delirium and age-
matched control subjects without delirium is 3.44 (95% confidence interval,
1.18–3.77). This effect is sustained over 12 months, adjusted for covariates
(McCusker et al. 2002).

Accelerated Death
Delirium may also hasten death among patients who die from other causes,
especially cancer. Among Mayo Clinic psychiatrically consulted medical-
surgical inpatients who died within a year of hospitalization, the mean time to
death was 122 days for patients with delirium and 218 days for patients with-
out delirium (Tennen and Rundell 2008). Patients with cancer and delirium
who died had a mean time to death of 60 days.

Morbidity
The more severe the delirium is, the poorer the outcome for the patient (Mar-
cantonio et al. 2002). The agitation or lethargy associated with delirium can
produce significant medical complications, including decreased oral intake,
pulmonary emboli, aspiration, and decubitus ulcers (Fong et al. 2009).
 Delirium 99

Health Care Costs

After adjusting for preexisting risk factors, researchers have found that delir-
ium is an independent determinant of duration of hospital stay, duration of
ICU stay, rate of postdischarge institutionalization, nursing time per patient
per day, and higher per-day hospital costs (Fong et al. 2009; Franco et al.
2001; Inouye 2008; Maldonado et al. 2009; Robinson et al. 2009; Siddiqi et
al. 2006). For patients with delirium, significant increases in medical costs re-
sult from additional consultations, nursing, and support services such as lab-
oratory testing and pharmacy (Fick et al. 2005; Millbrandt et al. 2004).

Predisposing Factors
Common Risk Factors
Several common risk factors predispose patients to delirium (Inouye 2006;
Robinson et al. 2009):

• Age over 65 years

• Dementia (two-thirds of delirium patients have underlying dementia)
• Visual or hearing impairment
• Dehydration or malnutrition
• Multiple medications
• Multiple medical conditions
• Impaired functional status

Relationship of Predisposing Factors to Delirium Etiology

Delirium in higher-vulnerability patients (i.e., those with more risk factors pre-
disposing to delirium) is often the result of mild precipitants, such as urinary
tract infections and dehydration, which are treatable. By contrast, delirium in
lower-vulnerability patients (who tend to be resistant to mild precipitants) is
more likely to be the result of serious insults, such as head trauma, which are
not treatable.
Assertive management of remediable etiologies in vulnerable patients,
such as elderly individuals with dementia, can result in robustly positive re-
sponses. Figure 7–1 summarizes the relationship between patient vulnerabil-
ity and severity of precipitating factors in delirium.
100 Clinical Manual of Psychosomatic Medicine

DELIRIUM MORTALITY/MORBIDITY FACTORS

Predisposing Factors/ Precipitating Factors/

Vulnerability Etiologies
High Vulnerability Severe Etiology

Low Vulnerability Mild Etiology

Figure 7–1. Relationship between vulnerability and etiology in delirium.

Precipitating Factors and Etiologies

Delirium always has at least one etiology, often remediable or partly remedi-
able. Development of delirium is a complex interaction between predisposing
factors, context of care, and precipitating factors. Dozens of precipitants of de-
lirium have been reported; the more frequently reported are listed below.

Toxic Etiologies
Toxic etiologies of delirium that are related to substances or poisons and as-
sociated abstinence syndromes include the following:

• Medications (Table 7–1)—normal dosages of medications may produce

toxicity when polypharmacy results in hepatic enzyme inhibition or when
an individual is a slow metabolizer at one of the cytochrome P450 en-
zymes.
• Substances of abuse—cocaine, amphetamines, cannabis, sedative-hypnotics.
 Delirium 101

Table 7–1. Common medications associated with delirium

Analgesics: meperidine, opiates
Antibiotics: acyclovir, ganciclovir, amphotericin B, interferon, cephalosporins,
rifampin, isoniazid, ciprofloxacin
Anticholinergics: antihistamines, antispasmodics, atropine, benztropine,
scopolamine, tricyclic antidepressants, trihexyphenidyl, belladonna alkaloids
Anticonvulsants: phenobarbital, phenytoin, valproic acid
Antineoplastic drugs: methotrexate, tamoxifen, vinblastine, vincristine, asparaginase,
aminoglutethimide
Antiparkinsonian drugs: amantadine, bromocriptine, L-dopa
Cardiac drugs: beta-blockers, captopril, clonidine, digitalis, lidocaine, mexiletine,
methyldopa, quinidine, tocainide, procainamide
Corticosteroids
Sedative-hypnotics: barbiturates, benzodiazepines
Sympathomimetics: amphetamine, cocaine, ephedrine, epinephrine, phenylephrine,
theophylline
Others: cimetidine, disulfiram, lithium, metrizamide, ranitidine, quinacrine

• Withdrawal syndromes—alcohol, drug withdrawal delirium.

• Poisons—pesticides, solvents, lead, mercury.

Metabolic Etiologies
Delirium may result from neuropsychiatric effects of hypermetabolic or hypo-
metabolic states, including but not limited to the following:

• Acid-base balance abnormalities—acidosis, alkalosis

• Electrolyte disturbances—hyponatremia, hyperkalemia, hypokalemia
• Organ failure consequences—hepatic failure (e.g., serum ammonia eleva-
tion), renal failure (elevated creatinine)
• Burns—electrolyte disturbances, acid-base problems, organ failure
• Vitamin deficiencies—vitamin B12, folate, niacin, thiamine
• Endocrinopathies—hyperadrenalism, hypoadrenalism, hyperthyroidism,
hypothyroidism, hyperglycemia, hypoglycemia
102 Clinical Manual of Psychosomatic Medicine

Central Nervous System Conditions and Events

The following central nervous system (CNS) conditions and events can con-
tribute to delirium:

• CNS trauma—closed head injury, postoperative states, heatstroke, severe

burns
• Structural lesions—stroke, CNS tumors (primary and metastatic), subdu-
ral hematoma, hydrocephalus, abscess, hemorrhage
• Vasculitis
• Limbic encephalitis
• Seizure disorders—including complex partial seizures and partial status
epilepticus
• Hypertensive encephalopathy

Hypoxic Etiologies
Delirium can be caused by conditions or events, including the following, that
decrease delivery of oxygen to the CNS:

• Anemia—including acute blood loss

• Carbon monoxide
• Hypotension
• Pulmonary failure
• Cardiac failure—congestive heart failure, myocardial infarction, arrhyth-
mia, shock

Inflammatory Etiologies
Inflammatory etiologies of delirium include the following:

• CNS infections—meningitis, encephalitis

• CNS effects of systemic infections—syphilis, HIV, hepatitis, sepsis
 Delirium 103

Clinical Characteristics
Core Features
Delirium has a core set of clinical features that are virtually always present, and
other signs and symptoms that are occasionally present (American Psychiatric As-
sociation 2000; Cole et al. 2007). Cole et al. (2007) used the Confusion Assess-
ment Method (CAM; Inouye et al. 1990) to assess the frequency of core features
among 290 medical inpatients older than 65 years diagnosed with delirium. Ta-
ble 7–2 lists the frequency of various delirium symptoms in this population.
In addition, Cole et al. (2007) used a delirium rating measure to screen
elderly patients admitted to medical services. The patients were studied over
the course of their admissions. Three DSM-IV-TR symptoms—orientation
to person, hyperactivity, and inattention—were associated with recovery in
these patients. The authors recommended that these three symptoms be em-
phasized when screening elderly medical inpatients for delirium.

Table 7–2. Frequency (%) of symptoms in an elderly medical

inpatient population diagnosed with delirium
Confusion Assessment Method (CAM) item* Percentage identified

Acute onset* 100

Inattention* 100
Disorientation* 100
Fluctuation* 100
Memory impairment* 99
Psychomotor changes (agitation or retardation) 87
Altered level of consciousness* 59
Altered sleep-wake cycle 59
Perceptual disturbance* 25
Note. *Indicates DSM-IV-TR criteria item.
Source. Adapted from Cole et al. 2007.
104 Clinical Manual of Psychosomatic Medicine

Prodromal and Subsyndromal States

Some patients manifest mild to moderate prodromal and subsyndromal de-
lirium symptoms, such as restlessness, anxiety, irritability, distractibility, or
sleep disruption. How to differentiate subsyndromal symptoms from prodro-
mal ones is not yet known, suggesting that assertive evaluation for potential
delirium etiologies is important when these early or milder symptoms and
signs emerge.

Psychomotor Variations
Patients with delirium may be hyperkinetic (psychomotor agitation), hypoki-
netic (somnolent or stuporous), or mixed (alternating between hyperkinetic
and hypokinetic).

Frequency
Hyperkinetic delirium represents 15%–45% of delirium cases, hypokinetic
delirium 20%–30%, and mixed delirium 25%–50% (J.R. Rundell, “Review
of 129 Articles Between 2000 and 2008 Discussing Frequency, Mortality and
Morbidity of Delirium in Inpatient Medical-Surgical Facilities,” unpublished
data, 2009). Variation in reported proportions can be accounted for by dif-
ferences in clinical setting, patient populations, and definitions used.

Prognosis
Hypokinetic delirium patients have the worst prognosis in terms of illness se-
verity, length of stay, mortality, and morbidity (J.R. Rundell, “Review of 129
Articles Between 2000 and 2008 Discussing Frequency, Mortality and Mor-
bidity of Delirium in Inpatient Medical-Surgical Facilities,” unpublished
data, 2009). Hypokinetic delirium is more likely than hyperkinetic delirium
to be underrecognized and undertreated.

Complications
The higher frequency of medical-surgical complications in patients with
hypokinetic delirium may be partly due to their being more severely ill to be-
gin with (Rundell 2008), and partly due to a higher risk of nosocomial infec-
tions, falls, venous thromboses, pressure sores, and aspiration because of the
hypokinesis.
 Delirium 105

Temporal Course
Initial Phase of Delirium
Three features of the temporal course of acute delirium are characteristic and
assist in differential diagnosis:

• Abrupt acute or subacute onset of symptoms

• Fluctuation of symptom severity during an episode—relatively lucid in-
tervals alternating with more severe symptoms
• Subsyndromal or prodromal signs and symptoms

Persistence of Cognitive Dysfunction

Jackson et al. (2004) reviewed seven prospective studies of patients who devel-
oped delirium as inpatients and were compared over time (median 2 years)
with control patients without delirium. Four studies showed that patients with
delirium had lower scores over time on cognitive measures, and three studies
found a higher incidence of dementia in patients with a history of delirium.

Characteristic Neuropsychiatric Impairments

on Mental Status Examination
Impaired Attention and Concentration
The patient with delirium has difficulty sustaining attention and is usually
either distractible or unable to focus.

Impaired Short-Term Memory

In the presence of impaired attention and registration, memory difficulties in
patients with delirium are secondary unless a patient has preexisting dementia.
After recovering from delirium, some patients are amnestic for the entire epi-
sode, others have islands of memory, and a few will recall the entire episode.

Disorientation
Disorientation to time and place is typical in patients with delirium.

Changes in Level of Consciousness

Level of consciousness varies from hyperalert in a patient with hyperkinetic de-
lirium to stuporous or comatose in a patient with severe hypokinetic delirium.
106 Clinical Manual of Psychosomatic Medicine

Impaired Visuospatial Skills

Patients with delirium often have visuoconstructional impairment and have
difficulty drawing simple geometric designs or drawing more complex figures
such as a clock face. Clock face drawing requires input from the following:

• Nondominant parietal cortex for overall spatial proportions and relations

• Dominant parietal cortex for details such as numbers or hands
• Prefrontal cortex for understanding the concept of time

Disturbed Executive Functions

Many higher-level executive functions are dependent on the prefrontal cortices
and are affected by delirium. These functions include switching mental sets, ab-
straction, sequential thinking, verbal fluency, and judgment (Trzepacz 1994).

Disorganized Thought Processes

Patients with delirium often have disorganized thought patterns. The severity
of the thought disturbance can range from tangentiality and circumstantiality
to loose associations. At the most severe level of thought disorganization,
speech may resemble a fluent aphasia (Wise and Trzepacz 1999).

Impaired Language and Speech

Language and speech impairments in patients with delirium range from mild
dysarthria or mumbling to dysphasia or muteness. Word-finding difficulty,
dysnomia with paraphasias, and reduced comprehension are common.

Perceptual Disturbances
The patient with delirium often experiences misperceptions, usually illusions
or hallucinations. Perceptual disturbances can be auditory or visual; visual il-
lusions and hallucinations are more common than auditory.

Diagnosis
Components of Diagnostic Assessment
1. History. Establishing a time line is vital to understanding temporal asso-
ciations of potentially related medical conditions or events. Although
 Delirium 107

temporality does not equate to causality, it raises the index of suspicion

and helps prioritize evaluation and management recommendations.
2. Physical and neurological examination, including vital signs.
3. Medication review. Dosage initiation or changes should be correlated with
behavior changes.
4. Mental status examination. The clinician should use standardized formats
that can be repeated over time (e.g., clock drawing, Mini-Mental State
Examination).
5. Electrocardiogram.
6. Chest X ray.
7. Electroencephalogram and lumbar puncture, if indicated.
8. Laboratory tests. The following should be tested: electrolytes, glucose, cal-
cium, liver function, renal function, magnesium, complete blood count,
serum drug levels, urine drug levels, and oxygen saturation or arterial blood
gases.

Differential Diagnosis
The differential diagnosis of delirium is extensive. Delirium may have multi-
ple etiologies. Francis et al. (1990) found that 55% of elderly patients with de-
lirium had a single definite or probable etiology, and the remaining 45% had
an average of 2.8 etiologies per patient.
Differentiating delirium from dementia and depression is particularly im-
portant because considerable comorbidity among these three conditions (“the
3 Ds”) exists (Trzepacz et al. 2011; see Table 7–3).

Electroencephalogram Findings
Almost all cases of delirium show diffuse slowing (delta waves) on the electro-
encephalogram. Although other electroencephalographic patterns are sugges-
tive of particular delirium etiologies (Kennard et al. 1945; Trzepacz 1994), none
are pathognomonic.

Diagnostic Instruments
Several instruments are available that measure a broad range of symptoms of
delirium and can be used for screening purposes or to quantitate symptom se-
verity over time.
Table 7–3. The 3 Ds: delirium, dementia, and depression

108 Clinical Manual of Psychosomatic Medicine

Delirium Dementia Depression

Onset Acute or subacute Chronic Subacute/variable

Course Fluctuating Progressive Variable
Reversibility Common Rare Remission
Orientation Impaired Impaired late Clear
Attention Impaired Impaired late Impaired
Memory Impaired Impaired Intact
Hallucinations Usually visual Visual or auditory Auditory
Delusions Fleeting/fragmented More fixed Mood congruent

Source. Adapted from Trzepacz et al. 2011.

 Delirium 109

Confusion Assessment Method

The CAM (Inouye et al. 1990) is an algorithm of four cardinal symptoms of
delirium intended for use in high-risk settings by nonpsychiatric clinicians.
The CAM can be supplemented by more intensive interviews to diagnose de-
lirium.

Delirium Rating Scales

The Delirium Rating Scale (DRS; Trzepacz et al. 1988) and the substantially
revised DRS-R-98 (Trzepacz et al. 2001) can help distinguish delirium from
dementia, schizophrenia, depression, and other medical conditions; it is avail-
able in several languages.

Memorial Delirium Assessment Scale

The Memorial Delirium Assessment Scale (MDAS; Breitbart et al. 1996) is a
10-item severity rating scale that is used after a patient has been diagnosed
with delirium and in serial examinations.

Prevention
Prevention is the most effective delirium management principle. Attention to
the following six factors, all of which can be addressed by nursing staff in the
general hospital, reduces delirium frequency (15% vs. 10%), number of de-
lirium episodes, and delirium duration (Inouye et al. 1999):

1. Frequent orientation
2. Noise reduction protocol—attention to a quiet environment, and normal-
izing lighting for as normal a sleep-wake cycle as possible
3. Early mobilization—encouraging ambulation and mobility as soon as
possible, especially after surgery, and continuing on a regular and increas-
ing basis
4. Visual aids—ensuring that spectacles are on the patient’s head and not on
the bedside stand
5. Hearing aids—ensuring that patients with hearing aids are wearing them
6. Hydration—assertive attention to intake, output, and serum electrolytes
110 Clinical Manual of Psychosomatic Medicine

Management and Symptomatic Treatment

Management and symptomatic treatment of delirium have two separate and
important goals. The first is critical and bears directly on the survival of the
patient: to identify and reverse, when possible, the reason(s) for the delirium.
The second is to reduce neuropsychiatric symptoms of delirium with environ-
mental and pharmacological interventions (American Psychiatric Association
1999).

Identification and Reversal of Remediable Etiologies

Careful attention to diagnostic assessment, as summarized in the “Diagnosis”
section earlier in this chapter, is important to identify remediable etiologies.
Construction of a time line to identify and prioritize potentially related med-
ical conditions or events is a key component of this assessment.

Reduction of Symptoms
Environmental Management of Delirium Signs and Symptoms
Preventive measures, implemented by the entire health care team, can be effec-
tive once delirium has occurred or when a prodrome is evident. The need to use
pharmacological symptomatic treatment indicates a failure of prevention. The
health care team can apply the following measures, which may obviate the need
for pharmacotherapy in some patients and reduce pharmacotherapy require-
ments in others:

1. Monitor vital signs, fluid intake and output, and oxygenation.

2. Avoid sleep interruptions whenever possible.
3. Place the patient in a room near the nursing station.
4. Arrange for a sitter if safety is a potential issue.
5. Maintain the bed in a low position; exercise caution with the use of side
rails.
6. Avoid placing delirious patients in a room together.
7. Encourage presence of family members; educate patients and families
about delirium.
8. Provide familiar objects and visual cues, such as family photos, clocks,
and calendars.
 Delirium 111

9. Provide adequate lighting, including a night-light at night.

10. Minimize transfers; perform procedures in the patient’s room when pos-
sible.
11. Maximize staff continuity and familiarity.
12. Reduce excessive environmental stimuli.
13. Repeatedly orient the patient to staff, surroundings, and situations.
14. Make sure glasses and hearing aids are used.
15. Use mechanical restraints only as a last resort, when potential danger to
patient or others cannot be addressed by other environmental measures or
by chemical restraint.

Pharmacological Management of Delirium Signs and Symptoms

Medications are used when an etiology of delirium is not immediately reme-
diable and when hyperactive signs and symptoms produce clinical or safety
complications. Antipsychotics are most commonly used; the most frequently
used nonantipsychotic medication is lorazepam, which may be administered
instead of or along with an antipsychotic.
There is scant evidence to support the use of psychotropic medications in
managing hypoactive delirium.
Evidence base for antipsychotic medication treatment of delirium target
symptoms. There are more than a dozen studies of pharmacological man-
agement of delirium symptoms conducted in well-designed prospective par-
adigms that included severity ratings and structured assessments (Seitz et al.
2007). No double-blind, placebo-controlled clinical trials have been con-
ducted; giving placebo medications to patients with such a potentially lethal
condition may be unethical.

• Equivalent clinical responses—Clinical improvement of delirium signs and

symptoms has been reported with the medications studied: chlorproma-
zine, haloperidol, quetiapine, olanzapine, and risperidone. No clinical ben-
efit has been demonstrated for one antipsychotic medication over another
in terms of target symptoms of delirium, although the medications have
different adverse effects (Fong et al. 2009).
• Lorazepam versus haloperidol—A 2004 review identified nine studies com-
paring haloperidol with lorazepam. In the only double-blind study, halo-
112 Clinical Manual of Psychosomatic Medicine

Table 7–4. Antipsychotic medication management of delirium

symptoms: average daily dosages
Medication Average daily dosage (range)

Haloperidol (all forms) 5.9 mg (0.5–30 mg)

Oral haloperidol 3.2 mg (0.5–20 mg)
Intramuscular haloperidol 6.5 mg (0.5–17.5 mg)
Intravenous haloperidol 7.3 mg (0.5–30 mg)
Olanzapine 6.2 mg (2.5–20 mg)
Quetiapine 100.4 mg (12.5–1,000 mg)
Risperidone 2.8 mg (0.25–35 mg)
Ziprasidone 101.8 mg (20–160 mg)
Source. Adapted from Rundell 2008.

peridol was found to be more effective. The other eight studies were open-
label and found the two drugs to be similar in efficacy (Khasati et al. 2004).
Lorazepam was more likely to cause sedation and worsening of symptoms;
haloperidol was more likely to have QTc prolongation. The authors con-
cluded that haloperidol would be a superior first choice, although loraz-
epam, either alone or in combination with haloperidol, would be an accept-
able alternative, particularly for patients with cardiac risks.

Medication management guidelines.

• Frequently used antipsychotic medications—At Mayo Clinic, the five antipsy-

chotic medications most frequently used in pharmacological management
of delirium symptoms are haloperidol, olanzapine, quetiapine, risperidone,
and ziprasidone (Rundell 2008) (see Table 7–4). Haloperidol has a number
of clinical advantages, including its availability as a parenteral formulation,
its low cost, and decades of experience in seriously ill patients. Other anti-
psychotics have advantages for particular subgroups of patients with delir-
ium (e.g., patients with Parkinson’s disease and other movement disorders,
patients with severe insomnia).
 Delirium 113

• Antipsychotic medication dosages—Dosage ranges vary among all medica-

tions used. Starting dosages are often difficult to determine. At Mayo
Clinic, daily dosage ranges for frequently used antipsychotic medications
administered in the inpatient medical-surgical setting vary considerably
(Rundell 2008), as shown in Table 7–4.
• Haloperidol for hyperactive delirium symptoms—Starting doses and adminis-
tration guidelines (Mayo Clinic Delirium Workgroup 2007 [unpublished])
for haloperidol in the management of hyperactive delirium symptoms are
provided in Table 7–5.

Table 7–5. Haloperidol management of hyperactive delirium:

starting doses and administration guidelines
Starting doses

Agitation level
Mild: 0.5–2.5 mg
Moderate: 2.5–5.0 mg
Severe: 5.0–10.0 mg
Administration guidelines
For elderly patients, use a starting dose about half that recommended in Table 7–4.
Allow 30 minutes between parenteral doses and 60 minutes between oral doses
before readministering.
Check QT and QTc intervals if haloperidol is newly initiated or changed from
another antipsychotic.
For continued agitation, double the previous dose and monitor patient’s vital signs.
Once the patient is calm, add the total milligrams of haloperidol required; administer
the same number of milligrams over the next 24 hours.
If the patient remains calm, reduce the dose by 50% every 24 hours.
To convert haloperidol from intravenous to oral dosage, double the intravenous total
daily dosage and administer orally in two or three divided doses.

Source. Mayo Clinic Delirium Workgroup 2007 (unpublished).

114 Clinical Manual of Psychosomatic Medicine

Morbidity and Mortality Risks Associated

With Antipsychotic Medications
All antipsychotic medications may prolong the QT or QTc interval, but some
increase it more than others do. Most antipsychotic medications, including all
atypical antipsychotics, carry a black box warning regarding reports of in-
creased mortality in elderly patients with dementia-related psychosis who are
treated with antipsychotics. Although the relevance of studies that support the
black box warnings to short-term use for delirium symptoms is unclear, clini-
cians need to be aware of findings from these studies.

Associations Between Antipsychotic

Medication Use and Mortality
Fifteen of 17 antipsychotic medication trials of ziprasidone showed higher
mortality in treated patients than in nontreated patients; most deaths were due
to cardiac events (U.S. Food and Drug Administration 2005). A subsequent re-
view suggested elevated mortality for patients taking any antipsychotic medi-
cation (Gill et al. 2007). Although statistically significant, absolute elevations
of mortality risk are slight (e.g., 0.2%–2.2% absolute risk differences in the
landmark review by Gill et al. 2007). None of these studies were done in the
specific setting of delirium treatment.

Potential Reasons for Association Between

Antipsychotic Medications and Mortality
A number of possible reasons, apart from cardiac concerns, may explain the
association between antipsychotic medications and elevated mortality, espe-
cially in elderly patients with dementia. Sedation may lead to elevated risk for
choking, aspiration, and deep vein thromboses. Hypotension may lead to fall
and fracture risk.

Practice Guideline Recommendations

Although absolute causality has not been established, the presence of elevated
mortality risk suggests the importance of following the American Psychiatric
Association’s (1999) recommendation to check electrocardiograms before and
 Delirium 115

after initiating or changing an antipsychotic medication in a delirious hospi-

talized patient.

Prolongation of QT or QTc Interval

Caution should be exercised when the patient’s baseline QT interval is greater
than 436 milliseconds or the QTc is greater than 475 milliseconds, or when a
prior dose caused prolongation of the QTc interval from baseline (Tisdale et al.
2007). Evidence indicates that monitoring either the uncorrected QT interval
or the QTc interval may be helpful; Tisdale et al. (2007) found that each was
equally accurate in predicting haloperidol-associated torsade de pointes in a re-
view of ICU patients.

Risk of Torsade de Pointes

Prolonged cardiac conduction is associated with development of torsade de
pointes. The precise risk and frequency of torsade de pointes following anti-
psychotic administration is unknown.

• Reported frequency varies between 1/2,500 and 1/25 depending on clin-

ical setting (e.g., general medical unit or ICU treating overdose patients).
In one report of 1,100 consecutive ICU patients, intravenous haloperidol
was implicated in inducing torsade de pointes tachyarrhythmia in 4 pa-
tients (Wilt et al. 1993).
• Associated factors found to be present in patients who develop torsade de
pointes include preexisting advanced heart disease, doses of haloperidol
>35 mg over 24 hours, baseline elevated QTc interval, baseline bradycar-
dia, personal or family history of sudden death or syncope (suggestive of
familial long QT syndrome), concurrent use of other QT-prolonging
medications, hypokalemia, and hypomagnesemia (Tisdale et al. 2007).

Medication Management Alternatives

Administration of small doses of intravenous lorazepam, particularly in pa-
tients whose symptoms have not responded to haloperidol alone, often helps to
reduce agitation and decrease the amount of antipsychotics required. Benzodi-
azepines are the symptomatic treatment of choice in the setting of alcohol or
benzodiazepine withdrawal associated with delirium. Propofol, midazolam,
116 Clinical Manual of Psychosomatic Medicine

and sometimes dexmedetomidine are used for short-term or emergent behav-

ioral control when other alternatives in the ICU setting have been ineffective.

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 8
Dementia

D ementia is present in a substantial number of patients admitted to med-

ical and surgical inpatient units and is associated with longer lengths of stay
and higher costs for those patients than for patients without dementia. An es-
timated 2.4–4.5 million individuals in the United States have dementia, and
if no scientific advances reduce the incidence of dementia, the prevalence is
anticipated to increase to 11–18.5 million by 2050 (Holsinger et al. 2007).

Epidemiology
Prevalence
The prevalence of dementia increases with advancing age. The rate is 6%–8%
in individuals ages 65 years and older, and more than 30% in those older than
85 years (Knopman et al. 2003).

Incidence and Survival

Incidence rates of dementia are about 1% per year. Survival rates for patients
with dementia are lower than for individuals without dementia; however, sur-

119
120 Clinical Manual of Psychosomatic Medicine

vival is still relatively long, with a median survival of 6 years after the onset of
dementia symptoms. Therefore, the prevalence rate surpasses the incidence
rate (Knopman et al. 2003).

Clinical Features of Dementia

Decline and Sufficient Impairment

• The person with dementia demonstrates a decline from his or her previous
level of functioning.
• The impairment is sufficient to cause disruption in social and occupa-
tional activities.

Multiple Cognitive Deficits

Multiple cognitive deficits are present that include memory impairment (the
ability to learn, retain, and retrieve newly acquired information) and at least
one of the following (Holsinger et al. 2007; Knopman et al. 2003):

• Aphasia—impaired ability to comprehend and express verbal information

• Apraxia—impaired ability to execute motor activities despite intact motor
abilities, sensory function, and comprehension of the required task
• Agnosia—failure to recognize or identify objects despite intact sensory
function
• Disturbance in executive functioning—impaired ability to perform abstract
reasoning, plan for future events, solve problems, maintain focus despite
distraction, and manipulate more than one idea at a time

Memory Impairment
Memory impairment as a primary feature does not encompass all dementias.
For example, memory is relatively spared in primary progressive aphasia and
frontotemporal dementia (Holsinger et al. 2007).

Neurological Disorders
The definition of dementia includes neurological disorders, such as head
trauma, that are associated with cognitive impairment and disruption in func-
 Dementia 121

tioning but are not progressive. The definition does not include impairment
due to Axis I disorders or delirium (American Psychiatric Association 2000).

Mild Cognitive Impairment

Definition
Cognitive dysfunction without functional decline. Individuals who have
cognitive dysfunction beyond what is expected for normal aging but do not
have functional decline as seen in dementia are said to have mild cognitive im-
pairment (MCI).
At least one cognitive domain affected. In MCI, cognitive dysfunction af-
fects at least one cognitive domain, most commonly recent memory as dem-
onstrated by impaired performance on delayed recall (referred to as the amnesic
type).

Prevalence and Incidence

The reported prevalence and incidence of MCI vary widely because of incon-
sistencies in the way the diagnostic criteria are used and the frequency of co-
morbid depression. Findings from some studies have suggested that up to
60% of patients with MCI who progress to Alzheimer’s disease (AD) have de-
pression (Chertkow et al. 2008).

Risk of Progression to Dementia

The risk of progression from MCI to dementia is high. The risk of developing
dementia is 5–10 times higher for individuals with MCI than for individuals
with normal cognition (Knopman et al. 2003).

Risk Factors for Dementia

• Age is the strongest risk factor for dementia, especially for AD.
• Baseline cognitive impairment.
• Family history. The relative risk of dementia in individuals with at least one
first-degree relative with AD is 3.5, and the risk is higher for female rela-
tives than males (Green et al. 2002; van Duijn et al. 1991). Familial risk is
greater for early-onset dementia (Silverman et al. 2003) and for African
Americans (Green et al. 2002).
122 Clinical Manual of Psychosomatic Medicine

• Genetic factors. The allele producing the ε4 type of apolipoprotein E

(APOE*E4) has the strongest evidence for a genetic risk factor in late-life
nonfamilial AD (Li et al. 2008).
• Vascular factors. Vascular disease is a risk factor for most dementias, includ-
ing AD. Diabetes mellitus, hypercholesterolemia, and tobacco smoking
have been associated with a higher risk of AD, whereas hypertension, an-
gina, and atrial fibrillation have been associated with accelerated decline in
patients with AD (Viswanathan et al. 2009).
• Other. Lack of alcohol consumption (compared with consumption of only
1–2 drinks per day), low body mass index (<18.5), low educational at-
tainment, and history of coronary bypass surgery may also be risk factors
(Barnes et al. 2009).

Major Types of Dementia

Alzheimer’s Disease
Prevalence
AD is the most common cause of dementia in elderly people. AD accounts for
at least 50%–60% of all dementias, and up to 80% if combined with other
pathological lesions (Knopman et al. 2003).

Pathophysiology
The accumulation of β-amyloid peptide is primary in the pathogenesis and
leads to neuritic plaques. Formation of neurofibrillary tangles is considered to
be secondary to the deposition of β-amyloid (Cummings 2004).

Key Diagnostic Features

The DSM-IV-TR (American Psychiatric Association 2000) diagnostic criteria
for dementia of the Alzheimer’s type are listed in Table 8–1. The following are
important features:

• The pattern of progression varies, but most often recent memory impair-
ment is observed first, with pervasive forgetfulness demonstrated through
repetitive questions and statements.
 Dementia 123

• Deficits in executive function, such as problems with paying bills or pre-

paring a meal, are generally seen early in the course of the disease.
• Motor and sensory deficits, incontinence, gait disturbances, and seizures
are evident late in the disease (Cummings 2004).

Neuropsychiatric Symptoms
The following neuropsychiatric symptoms are common in AD:

• Depression prevalence estimates among patients with AD vary widely, but

most estimates range from 30% to 50%, which suggests that major depres-
sive syndrome of AD may be among the most common mood disorders of
late life. A high rate of major depressive episodes occurs at or after the onset
of cognitive decline (Zubenko et al. 2003).
• Agitated or aggressive behaviors occur in up to 70% of patients with AD.
• Delusions or hallucinations are seen in 30%–50% of patients with AD. Psy-
chotic symptoms usually present in the later stages of disease.

Neuropsychiatric symptoms typically result in longer hospital stays, a

higher rate of nursing home placement, increased cost, and more caregiver
stress (Kales et al. 2007; Sink et al. 2005; Sultzer et al. 2008).

Dementia Due to Cerebrovascular Disease

Prevalence
The prevalence of pure vascular dementia ranges from 10% to 15%, or about
one-fifth that of AD, and an additional 20% of patients have a combination of
vascular dementia and AD. The definition of dementia due to cerebrovascular
disease generally includes pure vascular dementia and vascular dementia com-
bined with AD (Knopman et al. 2003).
Pathophysiology
Cerebrovascular disease is most often secondary to atherosclerotic disease or
amyloid angiopathy. Rarely, autoimmune mechanisms are the etiology. Cere-
bral injury can be caused by large-vessel infarctions, multiple lacunar infarc-
tions, extensive subcortical and periventricular white matter disease, and mi-
crovascular changes (American Psychiatric Association Work Group 2007).
124 Clinical Manual of Psychosomatic Medicine

Table 8–1. DSM-IV-TR diagnostic criteria for dementia of the

Alzheimer’s type
A. The development of multiple cognitive deficits manifested by both
(1) memory impairment (impaired ability to learn new information or to recall
previously learned information)
(2) one (or more) of the following cognitive disturbances:
(a) aphasia (language disturbance)
(b) apraxia (impaired ability to carry out motor activities despite intact
motor function)
(c) agnosia (failure to recognize or identify objects despite intact sensory
function)
(d) disturbance in executive functioning (i.e., planning, organizing,
sequencing, abstracting)
B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in
social or occupational functioning and represent a significant decline from a
previous level of functioning.
C. The course is characterized by gradual onset and continuing cognitive decline.
D. The cognitive deficits in criteria A1 and A2 are not due to any of the following:
(1) other central nervous system conditions that cause progressive deficits in
memory and cognition (e.g., cerebrovascular disease, Parkinson’s disease,
Huntington’s disease, subdural hematoma, normal-pressure
hydrocephalus, brain tumor)
(2) systemic conditions that are known to cause dementia (e.g.,
hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency,
hypercalcemia, neurosyphilis, HIV infection)
(3) substance-induced conditions
E. The deficits do not occur exclusively during the course of a delirium.
F. The disturbance is not better accounted for by another Axis I disorder (e.g.,
major depressive disorder, schizophrenia).
Code based on presence or absence of a clinically significant behavioral disturbance:
294.10 Without behavioral disturbance: if the cognitive disturbance is not
accompanied by any clinically significant behavioral disturbance.
294.11 With behavioral disturbance: if the cognitive disturbance is accompanied
by a clinically significant behavioral disturbance (e.g., wandering, agitation).
 Dementia 125

Table 8–1. DSM-IV-TR diagnostic criteria for dementia of the

Alzheimer’s type (continued)
Specify subtype:
With early onset: if onset is at age 65 years or below
With late onset: if onset is after age 65 years
Coding note: Also code 331.0 Alzheimer's disease on Axis III. Indicate other
prominent clinical features related to the Alzheimer’s disease on Axis I (e.g., 293.83
mood disorder due to Alzheimer’s disease, with depressive features, and 310.1
personality change due to Alzheimer’s disease, aggressive type).

Source. Reprinted from American Psychiatric Association: Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association,
2000, pp. 157–158. Used with permission.

Key Diagnostic Features

DSM-IV-TR diagnostic criteria for dementia with cerebrovascular disease are
listed in Table 8–2. The following are important clinical features:

• The onset or significant worsening of cognitive impairment occurs within

3 months of a clinically recognized stroke.
• Evidence of bilateral brain infarctions that involve cortical or subcortical
gray matter structures is present on neuroimaging.
• Controversy exists regarding the significance of magnetic resonance imag-
ing (MRI)–confirmed white matter hyperintensities in the diagnosis of
cerebrovascular dementia. White matter hyperintensity is a nonspecific
marker for cerebrovascular disease and does not confirm the diagnosis of
cerebrovascular dementia.
• A specific pattern of cognitive dysfunction is not seen with cerebrovascular
dementia, although attentional and executive functioning deficits may be
more prominent than short-term memory impairment.
• The prognosis is worse than that of AD. The median survival rate is 3 years
(Knopman et al. 2003).
126 Clinical Manual of Psychosomatic Medicine

Table 8–2. DSM-IV-TR diagnostic criteria for vascular dementia

A. The development of multiple cognitive deficits manifested by both
(1) memory impairment (impaired ability to learn new information or to recall
previously learned information)
(2) one (or more) of the following cognitive disturbances:
(a) aphasia (language disturbance)
(b) apraxia (impaired ability to carry out motor activities despite intact
motor function)
(c) agnosia (failure to recognize or identify objects despite intact sensory
function)
(d) disturbance in executive functioning (i.e., planning, organizing,
sequencing, abstracting)
B. The cognitive deficits in criteria A1 and A2 each cause significant impairment in
social or occupational functioning and represent a significant decline from a
previous level of functioning.
C. Focal neurological signs and symptoms (e.g., exaggeration of deep tendon
reflexes, extensor plantar response, pseudobulbar palsy, gait abnormalities,
weakness of an extremity) or laboratory evidence indicative of cerebrovascular
disease (e.g., multiple infarctions involving cortex and underlying white matter)
that are judged to be etiologically related to the disturbance.
D. The deficits do not occur exclusively during the course of a delirium.
Code based on predominant features:
290.41 With delirium: if delirium is superimposed on the dementia
290.42 With delusions: if delusions are the predominant feature
290.43 Without depressed mood: if depressed mood (including presentations that
meet full symptom criteria for a major depressive episode) is the predominant feature.
A separate diagnosis of mood disorder due to a general medical condition is not given.
290.40 Uncomplicated: if none of the above predominates in the current clinical
presentation
Specify if: With behavioral disturbance
Coding note: Also code cerebrovascular condition on Axis III.
Source. Reprinted from American Psychiatric Association: Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Associa-
tion, 2000, p. 161. Used with permission.
 Dementia 127

Dementia of Parkinson’s Disease and

Dementia With Lewy Bodies
Two subtypes of dementia are dementia of Parkinson’s disease and dementia
with Lewy bodies (DLB). Differential diagnosis depends on whether Parkin-
son’s disease precedes the onset of dementia (dementia of Parkinson’s disease)
or cognitive impairment is the predominant symptom (DLB).

Prevalence
Lewy body pathology is present in 10%–20% of patients with dementia at au-
topsy (Knopman et al. 2003).

Pathophysiology
Lewy inclusion bodies are seen in both cortical and subcortical regions. Pa-
thology associated with AD may also be seen in conjunction with Lewy body
pathology (American Psychiatric Association Work Group 2007).

Key Diagnostic Features

Diagnostic criteria for DLB are listed in Table 8–3. DLB is characterized by
the presence of at least two of the following symptoms:

• Parkinsonism, including muscular rigidity, resting tremor, bradykinesia,

postural instability, and parkinsonian gait disorder
• Prominent, fully formed visual hallucinations
• Substantial fluctuations in alertness or cognition
• Other clinical features
1. Rapid eye movement disorder is considered by some to be a key diag-
nostic feature (Knopman et al. 2003).
2. Increased sensitivity to extrapyramidal symptoms may be caused by
antipsychotic medications.
3. Psychiatric treatment is often necessary because of the high prevalence
of depression in Parkinson’s disease and associated psychotic symp-
toms (American Psychiatric Association Work Group 2007).
128 Clinical Manual of Psychosomatic Medicine

Table 8–3. Diagnostic criteria for dementia with Lewy bodies

A. On the basis of evidence from a patient’s history and mental status examination,
dementia with cerebrovascular disease is characterized by the presence of at least
two of the following impairments:
1. Impaired learning and impaired retention of new information
2. Impaired handling of complex tasks
3. Impaired reasoning ability
4. Impaired spatial ability and orientation
5. Impaired language
B. The impairments in criterion A notably interfere with work or usual social
activities or relationships with others
C. The impairments in criterion A represent a notable decline from a previous level
of functioning
D. Dementia with Lewy bodies is characterized by the presence of at least two of
the following symptoms:
1. Parkinsonism (muscular rigidity, resting tremor, bradykinesia, postural
instability, parkinsonian gait disorder)
2. Prominent, fully formed visual hallucinations
3. Substantial fluctuations in alertness or cognition
4. Rapid eye movement sleep behavior disorder
E. The impairments in criterion A do not occur exclusively during the course of
delirium
F. The impairments in criterion A are not better explained by a major psychiatric
diagnosis
G. The impairments in criterion A are not better explained by a systemic disease or
another brain lesion
Note. Rapid eye movement is an additional characteristic diagnostic feature.

Source. Based on the Consortium on Dementia With Lewy Bodies (McKeith et al. 1996) with
modifications by Knopman et al. (2003).
 Dementia 129

Frontotemporal Dementia
Prevalence
Frontotemporal dementia is relatively rare, but it accounts for 20%–50% of
dementia cases with age at onset of less than 65 years (Mendez et al. 2008).
Specific genetic defects have been identified, and approximately one-third of
the cases are familial (American Psychiatric Association Work Group 2007).

Pathophysiology
Frontotemporal lobar degeneration is seen on gross pathology, with circum-
scribed and often asymmetrical lobar atrophy. The previous term of “Pick’s
disease” referred to frontotemporal lobar degeneration with intranuclear in-
clusion bodies (Mendez et al. 2008).

Key Diagnostic Features

Criteria for frontotemporal dementia are listed in Table 8–4. The following
are also important features (Mendez et al. 2008):

• The primary features are changes in personality, behavior, and judgment;

therefore, the presentation of patients with frontotemporal dementia can
often mimic a psychiatric disorder.
• Changes in personality can range from apathy with loss of interest and ini-
tiative to elevated mood and disinhibition.
• Loss of insight occurs early in the disease; patients lack awareness into
their deficits and do not appreciate the consequences of their behavior.
Decreased empathy is also seen; patients appear indifferent and emotion-
ally unresponsive.
• Disturbances in social and moral behavior include physical aggressiveness,
sexually inappropriate behaviors, and loss of social manners.
• Eating behavior changes occur in about 80% of patients; changes include
hyperorality, carbohydrate craving, and indiscriminate eating (including
placing nonfood items in mouth).
• Repetitive acts of simple verbal and motor behaviors (e.g., hand clapping,
lip smacking), as well as more complex rituals (e.g., cleaning, hoarding,
checking), can develop.
130 Clinical Manual of Psychosomatic Medicine

Table 8–4. American Neuropsychiatric Association consensus

criteria for frontotemporal dementia
Core diagnostic features (all need to be present for diagnosis)
1. Insidious onset and gradual progression
2. Early decline in social interpersonal conduct
3. Early impairment in regulation of personal conduct
4. Early emotional blunting
5. Early loss of insight
Features that support the diagnosis
1. Decline in personal hygiene and grooming
2. Mental rigidity and inflexibility
3. Distractibility and impersistence
4. Hyperorality and dietary changes
5. Perseverative and stereotyped behavior
6. Utilization behavior
Source. Adapted from Mendez et al. 2008 and Neary et al. 1998.

Other Clinical Features

• Relative preservation of memory is a unique feature of frontotemporal de-

mentia. Visuospatial function can also be normal. Psychometric testing
demonstrates deficits primarily in tests of executive function.
• Prefrontal or anterior temporal atrophy on computed tomography (CT)
or MRI is useful in confirming frontotemporal dementia but is not nec-
essary to make the diagnosis.

Rapidly Progressive Dementias

Creutzfeldt-Jakob disease should be considered when a patient presents with
dementia of subacute onset, typically having lasted for weeks to months. Mo-
tor and cognitive symptoms are present early in the disease, and seizures may
develop later. The 14-3-3 protein in the cerebrospinal fluid is a useful marker
 Dementia 131

in supporting the diagnosis. Nonvasculitic autoimmune inflammatory men-

ingoencephalopathies, such as Hashimoto’s encephalopathy and Sjogren-
associated encephalopathy, can be misdiagnosed as Creutzfeldt-Jakob disease,
and the essential difference is that these latter dementias respond to high-dose
steroids (Knopman et al. 2003).

Differential Diagnosis
The differential diagnosis of dementia syndromes is summarized in Table 8–5.

Evaluation
Figure 8–1 shows a hierarchical approach to diagnosing MCI, dementia, and
the major subtypes of dementia. The components of a thorough evaluation, as
described in the following subsections, are important in diagnosis.

History

• A knowledgeable informant such as a family member, spouse, or friend is crit-

ical, because another person often recognizes cognitive deficits and per-
sonality changes before the patient does. Collateral history from a reliable
informant may be as useful as the brief screening instruments for detecting
dementia, although history from an informant combined with cognitive
testing is recommended.
• Consideration should be given to interviewing the spouse or family member
separately from the patient, because the informant may not be as forth-
coming with the patient present due to concerns about the patient’s reac-
tions.
• Data on subjective memory loss as an indicator of dementia are conflicting,
with some reports indicating that memory problems correlate more closely
with depressive symptoms and personality traits than with dementia (Hol-
singer et al. 2007).
• Assessment of daily activities may include questions about the patient’s abil-
ity to recall recent events and conversations, to balance a checkbook, and
to remember medications. Table 8–6 lists other important daily activities
that should be assessed.
132 Clinical Manual of Psychosomatic Medicine

Table 8–5. Differential diagnosis of dementias and subacute

confusional states
Irreversible conditions
Alzheimer’s disease
Dementia due to cerebrovascular disease
Dementia with Lewy bodies
Frontotemporal dementia
Progressive supranuclear palsy
Huntington’s disease
Creutzfeldt-Jakob disease
Paraneoplastic limbic encephalitis
HIV-associated dementia
Potentially reversible conditions
Toxic disturbances
Alcohol-related syndromes, including Wernicke-Korsakoff syndrome
Medication effects
Metabolic abnormalities
Vitamin B12 deficiency
↑↓ Thyroid level
Hepatic or renal failure
Electrolyte disturbances
Depressive disorders
Central nervous system infections: meningitis or encephalitis
Autoimmune and inflammatory encephalopathies
Lupus erythematosus
Hashimoto’s encephalopathy
Neurosarcoidosis
Brain structural lesions
Primary or secondary brain tumors
Subdural hematoma
Normal-pressure hydrocephalus
Head trauma
Acute stroke
 Dementia 133

Assessment of suspected cognitive dysfunction—

not delirium—by history and/or examination

Evaluate daily functioning with mental status examination/

psychometric testing and talking with informant

Normal ADL Abnormal ADL Normal ADL Abnormal ADL

Impaired MS Normal MS Normal MS Impaired MS

Mild cognitive Consider Cognitively

depression Dementia
impairment intact
Consider
frontotemporal
dementia
Reevaluate in Headache, seizures
1 year No Yes

Rapidly Yes Brain tumor,

progressive disorder subdural hematoma
No Yes

Temporal link to stroke or bilateral cerebral infarctions Other medical features

Yes No Yes No

Parkinsonism, Specific medical Creutzfeldt-Jakob disease,

Dementia with
prominent disorders: nonvasculitic autoimmune
cerebrovascular
hallucinations, infections, inflammatory
disease
arousal disorder metabolic, toxic meningoencephalopathies
Yes No

Dementia with Lewy bodies Dominant cognitive disorder

Anterograde amnesic Dysexecutive/behavioral Primary

syndrome of disorder of frontotemporal progressive
Alzheimer’s disease dementia aphasia

Figure 8–1. A hierarchical approach to diagnosing mild cognitive impair-

ment, dementia, and the major subtypes of dementia.
The sequence of decisions reflects a hierarchy of importance of diagnostic information:
features appearing earlier in the decision tree suggest diagnoses regardless of features
assessed later.
ADL=activities of daily living necessary for independent life, including complex ac-
tivities such as managing finances. MS=mental status, assessed through bedside men-
tal status testing or formal neuropsychological evaluations.
Source. Reprinted from Knopman DS, Boeve BF, Petersen RC: “Essentials of the
Proper Diagnoses of Mild Cognitive Impairment, Dementia, and Major Subtypes of
Dementia.” Mayo Clinic Proceedings 78:1302, 2003. Used with permission.
134 Clinical Manual of Psychosomatic Medicine

Table 8–6. Assessment of daily activities

Recalling recent events and conversations
Keeping track of personal items (e.g., keys, wallet, purse, glasses)
Writing checks, paying bills, balancing a checkbook
Assembling tax records, business affairs, or papers
Shopping alone for clothes, household necessities, or groceries
Playing a game of skill, working on a hobby
Heating water, making a cup of coffee, turning off stove
Preparing a balanced meal
Keeping track of current events
Paying attention to, understanding, discussing a TV show, book, or magazine
Remembering appointments, family occasions, holidays, medications
Traveling out of the neighborhood, driving, arranging to take buses
Source. Reprinted from Knopman DS, Boeve BF, Petersen RC: “Essentials of the Proper Diag-
noses of Mild Cognitive Impairment, Dementia, and Major Subtypes of Dementia.” Mayo Clinic
Proceedings 78:1301, 2003. Used with permission.

Mental Status Examination

Mini-Mental State Examination

• The Mini-Mental State Examination (MMSE; Folstein et al. 1975) is the

most studied of the brief cognitive tests with proven validity, but it may
often be insensitive in screening for MCI and mild dementia.
• Scores need to be adjusted for age and are influenced by education.

Other Cognitive Instruments

• The Short Test of Mental Status (Kokmen et al. 1991) is similar to the
MMSE, but it has added features that improve sensitivity in detecting
mild cognitive deficits (Tang-Wai et al. 2003).
• Table 8–7 lists brief cognitive tests used to screen patients. Instruments
that require more time but may increase accuracy include the Modified
Mini-Mental State Examination (Teng and Chui 1987) and the Montreal
 Dementia 135

Cognitive Assessment (Nasreddine et al. 2005; see also Feldman et al.

2008; Holsinger et al. 2003).

Laboratory Assessment
Laboratory assessment is outlined in Table 8–7. A patient’s medical comorbidities
need to be considered in the determination of appropriate laboratory screening.
Vitamin B12 levels and thyroid function tests are recommended for elderly pa-
tients suspected of having dementia, because vitamin B12 deficiency and hypothy-
roidism are not uncommon in this population and are easily treated.

Neuropsychological Testing
Table 8–7 indicates the potential uses of neuropsychological testing for pa-
tients with dementia.

Neuroimaging
Table 8–7 includes information about the use of neuroimaging for diagnostic
evaluation for dementia.

• Some experts support the use of neuroimaging (noncontrast CT or MRI)

for most patients during the initial evaluation of dementia to detect struc-
tural lesions such as brain neoplasms or subdural hematomas, but the
yield is very low if the patient has no focal signs.
• Medial temporal lobe atrophy, specifically hippocampal atrophy or ento-
rhinal atrophy, may support a diagnosis of AD (Knopman et al. 2001).

Treatment
Considerations for General Management
Review of Potential Contributions
A detailed review of potential contributions (e.g., infection, dehydration, pain)
to a patient’s neuropsychiatric symptoms is necessary before treatment is insti-
tuted, because addressing the concurrent problem may result in resolution of
agitation or aggression. Other considerations include visual or auditory impair-
ment and the level of environmental stimulation (Ballard et al. 2009a).
136 Clinical Manual of Psychosomatic Medicine

Table 8–7. Diagnostic evaluation for dementia

Brief cognitive tests
Examples: Mini-Mental State Examination, Montreal Cognitive Assessment, and
Short Test of Mental Status
Insufficient evidence to recommend one test over another
Failure to discriminate between dementia subtypes
Laboratory investigations
Thyroid-stimulating hormone
Serum vitamin B12
Serum electrolytes
Complete blood count
Liver function tests
Serum creatinine and blood urea nitrogen
Serum calcium
Serum fasting glucose
Other tests if clinically indicated
Serum folate
Fluorescent treponemal antibody absorption
Serum HIV
Serum and urine screens for alcohol, drugs, and heavy metals
Erythrocyte sedimentation rate
Arterial blood gases
Urinalysis
Chest X ray
Electrocardiogram
Lumbar puncture
Neuropsychological testing
Not required for a diagnosis of dementia
May assist with distinguishing between normal aging, mild cognitive impairment,
and dementia
May assess for other syndromes of cognitive impairment apart from dementia
May address the risk of progression from mild cognitive impairment to dementia
 Dementia 137

Table 8–7. Diagnostic evaluation for dementia (continued)

Neuroimaging and CSF
In some cases: structural neuroimaging with either a noncontrast CT or MRI scan in
routine evaluation of dementia
Not recommended for routine use: PET imaging and SPECT
For patients with rapid deterioration in cognition, or unexplained fever or elevated
white blood count: CSF examination
If Creutzfeldt-Jakob disease is suspected: CSF 14-3-3 protein

Note. CSF=cerebrospinal fluid; CT=computed tomography; MRI=magnetic resonance imaging;

PET=positron emission tomography. SPECT=single-photon emission computed tomography.
Source. Adapted from Feldman et al. 2008; Knopman et al. 2001; Tang-Wai et al. 2003.

Pain
Observational studies suggest that pain is undertreated among patients with
cognitive impairment. Assessment of pain in patients with dementia is a
needed area of research because existing pain rating scales are designed for
communicative patients (Scherder et al. 2005).

Management of Comorbid Medical Conditions

Management of comorbid medical conditions is essential. For example, con-
trol of hypertension and hyperlipidemia may stabilize vascular dementia.

Decisions Regarding Life-Prolonging Interventions

Decisions regarding life-prolonging interventions, such as intravenous fluids,
antibiotics, feeding tubes, and surgery, should respect the patient’s advance di-
rective and involve collaboration with the surrogate decision makers (Cum-
mings 2004).

Treatment of Cognitive Deterioration

Cognitive Training
The data are mixed regarding the effectiveness of cognitive training or cognitive
rehabilitation in improving or maintaining cognitive and functional perfor-
mance (Hogan et al. 2008). One meta-analysis showed that cognitive training
had a modest effect size on learning, memory, executive function, and activities
of daily living (Sitzer et al. 2006).
138 Clinical Manual of Psychosomatic Medicine

Cholinesterase Inhibitors

• Cholinesterase inhibitors may slow cognitive decline in patients with mild

to moderate dementia.
• Available cholinesterase inhibitors include donepezil, rivastigmine, galan-
tamine, and tacrine. Tacrine is rarely used due to hepatotoxicity.
• Side effects include nausea, vomiting, bradycardia, syncope, fatigue, and
abnormal dreams (Cummings 2004).

Memantine

• Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is

used either as monotherapy or as adjunctive therapy with a cholinesterase
inhibitor for patients with moderate to severe dementia.
• Side effects include dizziness, constipation, confusion, headache, and hy-
pertension (Hogan et al. 2008).

Other Medications
Insufficient evidence is available for the use of anti-inflammatory agents, hor-
mone replacement therapy, or vitamin E (Cummings 2004).

Nonpharmacological Interventions for Management

of Neuropsychiatric Symptoms
Because of the limited long-term efficacy and the adverse effects of pharma-
cological treatment, nonpharmacological interventions should be tried first in
most circumstances. Most studies that have evaluated the efficacy of nonphar-
macological interventions have been methodologically weak, but emerging
evidence supports the use of practical psychosocial treatments (Ayalon et al.
2006).
Randomized controlled trials (RCTs) have demonstrated that intensive 6-
to 12-month programs to educate staff in person-centered care resulted in
decreased use of psychotropic medications in nursing homes, with no increase
in patients’ behavioral problems (Fossey et al. 2006). Some evidence supports
the efficacy of validation therapy, a group-based treatment that focuses on em-
pathy for the patient and respecting the individual’s reality with activities that
involve movement and music (Ballard et al. 2009a).
 Dementia 139

Pharmacological Treatment of Agitation and Aggression

Typical Antipsychotics
Efficacy.

• Haloperidol, the typical antipsychotic that has been studied most exten-
sively, has been associated with modest improvement in symptoms of ag-
gression compared with placebo but has shown minimal benefit in treating
other symptoms of agitation (Ballard et al. 2009a). When adverse effects
are taken into account, the risks generally outweigh the benefits, especially
for long-term treatment, but this issue remains debatable.
• No data are available to suggest that one typical antipsychotic is more ef-
ficacious than another.
• RCTs have not been done to compare the efficacy of typical and atypical
antipsychotics in the treatment of dementia (Sink et al. 2005).

Adverse effects.

• The U.S. Food and Drug Administration (FDA) warning in 2005 about
increased mortality with the use of atypical antipsychotics for treatment of
dementia in elderly patients was extended to the typical antipsychotics in
2007. The warning came after studies suggested that the mortality rates
from typical antipsychotics are comparable to or higher than those from
atypical antipsychotics (Gill et al. 2007; Wang et al. 2005).
• One study showed that the risk of death was increased with higher dos-
ages. The relative risk was 1.14 with low dosages (less than the median
dosage) and 1.73 with high dosages (greater than the median) (Wang et al.
2005). The absolute risk, however, is still quite low.
• Other serious adverse effects include dystonia, parkinsonism, tardive dys-
kinesia, and QTc prolongation.

Atypical Antipsychotics.
Efficacy.

• Atypical antipsychotics are the most commonly used pharmacological

treatment for agitation and psychosis in patients with dementia.
140 Clinical Manual of Psychosomatic Medicine

• Most trials have studied efficacy over 6–12 weeks of treatment, and mod-
est benefit has been found for the treatment of aggression but not for non-
aggressive symptoms of agitation.
• One meta-analysis of RCTs found support for the use of risperidone and
aripiprazole but not olanzapine or quetiapine (Schneider et al. 2006).
• In the Clinical Antipsychotic Trials of Intervention Effectiveness—Alz-
heimer’s Disease (CATIE-AD) project (Sultzer et al. 2008), outpatients
with AD and psychosis or agitated/aggressive behavior were treated for up
to 36 weeks with olanzapine, quetiapine, risperidone, or placebo. Clinical
symptoms such as anger, aggression, and paranoid ideas improved some-
what with the atypical antipsychotics, but overall functioning and quality
of life did not change. Olanzapine and risperidone were associated with
improved Neuropsychiatric Inventory total scores. No significant change
occurred with quetiapine, although the dosage was relatively low because
of sedation with higher dosages. The mean dosages for olanzapine, que-
tiapine, and risperidone were 5.5 mg/day, 56.5 mg/day, and 1.0 mg/day,
respectively.
• Treatment beyond 6–12 months has generally not been found beneficial,
and/or the adverse effects outweigh the advantages (Ballard et al. 2009a).

Adverse effects.
Increased mortality. The FDA’s 2005 warning regarding the increased risk
of death with atypical antipsychotics was based on a review of RCTs that in-
cluded risperidone, olanzapine, quetiapine, and aripiprazole. Fifteen of the 17
trials showed a higher mortality rate, with an approximate rate of 1.6–1.7 over
12 weeks (but the absolute risk was small). Cardiac-related events and infec-
tion were the most common causes of mortality in these studies. The relation-
ship of antipsychotics and mortality is complex and not yet understood (Kales
et al. 2007).
Increased mortality with prolonged treatment. The dementia antipsychotic
withdrawal trial showed increased mortality for patients who were random-
ized to continue antipsychotic treatment than for those allocated to placebo,
with marked differences appearing between groups during periods of follow-
up longer than 12 months. Survival at 36 months was 30% for patients who
continued taking antipsychotics compared with 60% for patients taking pla-
cebo (Ballard et al. 2009b). In one study of patients who were very frail and
 Dementia 141

had a mean age of 86 years, antipsychotic use did not increase mortality or
hospital admissions at 2-year follow-up, but use of restraints doubled mortal-
ity (Raivio et al. 2007).
Cerebrovascular events. Risperidone has been associated with a threefold
risk of serious cerebrovascular events, and a similar risk has been demonstrated
with olanzapine, although this finding has been debated. If an association ex-
ists, it is likely related to the entire class of atypical antipsychotics (Ballard et
al. 2009a).
Cognitive decline. Acceleration in the rate of cognitive decline has been
demonstrated in patients treated with atypical antipsychotics compared with
those taking placebo over 12 weeks (Schneider et al. 2006).
Other adverse effects. Other adverse effects of atypical antipsychotics in-
clude sedation, parkinsonism, QTc prolongation, and metabolic syndrome.

Cholinesterase Inhibitors
Cholinesterase inhibitors, if maintained over 6 months, may provide mild im-
provement in anxiety and apathy, but no changes in agitation (Ballard et al.
2009a).

Antidepressants for the Agitation of Dementia

• In a comparison of citalopram and risperidone in an RCT of patients with
dementia but not depression, both medication groups experienced im-
provement, including decreased psychotic symptoms and agitation (Pol-
lock et al. 2007).
• The evidence does not support use of trazodone for the treatment of agi-
tation in patients with dementia of the Alzheimer’s type (Teri et al. 2000).
• Although some data are encouraging, further studies are needed before
treatment with antidepressants for agitation of dementia in nondepressed
patients is recommended.

Anticonvulsants
• Valproate is not indicated due to sedation with no demonstrated benefit in
the treatment of neuropsychiatric symptoms.
• Preliminary results show that carbamazepine can help in managing agita-
tion in patients with AD, but additional data are needed (Ballard et al.
2009a).
142 Clinical Manual of Psychosomatic Medicine

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 9
Eating Disorders

Although eating disorders are infrequently diagnosed in the medical setting,

eating disorder symptoms, such as restricted intake, uncontrolled eating, and
body image distress, are common in patients (Devlin et al. 2011). Eating dis-
orders are associated with high rates of all-cause mortality and suicide (Crow
et al. 2009), and eating disorder symptoms may complicate treatment of med-
ical illness.

Definitions and Clinical Features

Diagnostic Overlap
The course and outcome of eating disorders are associated with a substantial
degree of crossover from one eating disorder diagnosis to another. More than
half of patients with anorexia nervosa cross over between restricting and binge-
eating/purging subtypes, and about one-third cross over to bulimia but are
likely to relapse to anorexia. Patients with bulimia most often cross over to eat-
ing disorder not otherwise specified (Steinhausen and Weber 2009) and are less
likely to develop anorexia nervosa (Eddy et al. 2008).

145
146 Clinical Manual of Psychosomatic Medicine

Definition of Anorexia Nervosa

To be diagnosed with anorexia nervosa, a patient needs to meet four criteria as
defined by DSM-IV-TR (American Psychiatric Association 2000):

1. Refusal to maintain weight at or above minimally normal weight for

height and age (body weight is more than 15% below ideal weight)
2. Intense fear of weight gain or of becoming fat, despite being underweight
3. Severe body image disturbance in which body image is the predominant
measure of self-worth with denial of the seriousness of low body weight
4. In postmenarchal females, amenorrhea (i.e., absence of at least three men-
strual cycles)

Restricting or Binge-Eating/Purging Subtypes

of Anorexia Nervosa
Patients with the restricting subtype of anorexia nervosa primarily use restric-
tion of intake to reduce their weight, whereas those with the binge-eating/
purging subtype regularly engage in binge eating or purging (e.g., vomiting,
abuse of laxatives or diuretics) or both to control their weight. A patient with
anorexia may induce vomiting yet still be considered anorexic (rather than bu-
limic) if criteria for anorexia are met (American Psychiatric Association 2000).

Definition of Bulimia Nervosa

DSM-IV-TR criteria for bulimia nervosa include the following (American
Psychiatric Association 2000):

1. Episodes of binge eating occur with a sense of loss of control.

2. Binge eating is followed by compensatory behavior of the purging type
(e.g., self-induced vomiting, laxative abuse, diuretic abuse) or nonpurg-
ing type (e.g., excessive exercise, fasting, strict dieting).
3. Binges and compensatory behavior occur at least two times per week for
3 months.
4. Patient feels dissatisfaction with body shape and weight.

Eating Disorder Not Otherwise Specified

Patients with clearly aberrant eating patterns and weight management habits
who do not meet the criteria for anorexia nervosa or bulimia nervosa are diag-
 Eating Disorders 147

nosed with eating disorder not otherwise specified (NOS). The treatment liter-
ature has been predominantly focused on bulimia nervosa and anorexia nervosa,
although eating disorder NOS is the most common eating disorder (Crow and
Peterson 2009). One example of eating disorder NOS is binge-eating disorder,
which is currently a research diagnosis requiring patients to meet three of the
five following criteria (American Psychiatric Association 2000, p. 787):

1. Eating much more rapidly than normal

2. Eating until uncomfortably full
3. Eating large amounts of food when not feeling physically hungry
4. Eating alone because of embarrassment about how much one is eating
5. Feeling disgusted, depressed, or very guilty after overeating

Night Eating Syndrome

Night eating syndrome is characterized by evening hyperphagia (eating more
than one-third of total daily calories after the evening meal) and nocturnal
awakenings with ingestion of food. It is likely to co-occur with substance use
disorders, use of atypical antipsychotics, and obesity (Lundgren et al. 2006).

Epidemiology
Prevalence
Lifetime prevalence estimates of anorexia nervosa, bulimia nervosa, and
binge-eating disorder are 1%, 1.5%, and 3.5%, respectively, among women,
and 0.3%, 0.5%, and 2.0%, respectively, among men (Hudson et al. 2007).

Chronic Course of Illness

Less than half of patients with bulimia have full recovery, and 25% have a
chronic protracted course (Steinhausen and Weber 2009). In one study, two-
thirds of women with anorexia nervosa showed clinical recovery by 5 years,
with no difference in recovery between cases that had been detected and cases
that were undetected in the medical system (Keski-Rahkonen et al. 2007).
The mean lifetime duration of binge-eating disorder is 14 years, significantly
longer than that of bulimia nervosa or anorexia nervosa, each of which has a
mean duration of about 6 years (Pope et al. 2006).
148 Clinical Manual of Psychosomatic Medicine

Comorbid Psychiatric Illness With High Rates

of Anxiety Disorders
Two-thirds of patients with anorexia and bulimia nervosa have had one or
more anxiety disorders in their lifetime, most commonly obsessive-compulsive
disorder and social phobia. For the majority of patients, the onset of the anxiety
disorder occurs in childhood before development of the eating disorder (Kaye
et al. 2004). Comorbid depression and substance use frequently co-occur; al-
cohol use is more often associated with bulimia nervosa and the binge-eating/
purging subtype of anorexia nervosa than with the restricting type of anorexia
nervosa (Bulik et al. 2004; Halmi et al. 1991).

Increased Mortality
Mortality rates for anorexia and bulimia nervosa are approximately 4%. Al-
though eating disorder NOS is sometimes viewed as less serious than the other
eating disorders, it has a similar mortality rate (Crow et al. 2009).

Pathogenesis
The etiology of eating disorders is multifactorial and includes genetics, central
nervous system abnormalities, personality traits, cultural influences, and fam-
ily environment. Substantial evidence supports the familial aggregation of eat-
ing disorders, and twin studies show higher rates among monozygotic twins
than among dizygotic twins. Personality traits such as perfectionism, impul-
sivity, and negative affect are potential risk factors (Yager and Andersen 2005).

Assessment and Differential Diagnosis

Assessment
Assessment of patients in the medical setting is challenging for many reasons, in-
cluding the difficulty of determining whether behaviors such as vomiting or food
restriction are due to somatic illness or psychological factors. Patients with eating
disorders are often secretive about their illness and may deny the severity. A thor-
ough history is the most important part of the assessment, and no diagnostic tests
are required to make a diagnosis unless the history suggests an organic etiology.
 Eating Disorders 149

1. Physical assessment. The physical examination should focus on evidence of

dehydration, lanugo, acrocyanosis, salivary gland enlargement, and scar-
ring on the dorsum of the hand (Russell’s sign). The patient should also
be checked for orthostatic hypotension and body mass index. Patients
who purge need a dental examination.
2. Laboratory assessment. The laboratory evaluation is individualized for each
patient but typically includes serum electrolytes, blood urea nitrogen and
creatinine, liver enzymes, serum albumin, thyroid function, complete
blood cell count, and urinalysis. For patients who are severely malnour-
ished, the assessment includes calcium, magnesium, and phosphate levels
and an electrocardiogram. Serum amylase may be considered for patients
suspected of self-induced vomiting but is not sufficiently sensitive or spe-
cific to be a useful routine screening tool.
3. Other studies to consider. Dual-energy X-ray absorptiometry of bone may
be used for patients who have been chronically underweight. Magnetic
resonance imaging (MRI) or computed tomography (CT) of the brain
may be needed for patients who have persistent cognitive impairment or
other mental status changes despite weight restoration (American Psychi-
atric Association 2006).

Differential Diagnosis
Preoccupation with body image or the presence of intentional weight manip-
ulation is helpful in differentiating an eating disorder from other medical eti-
ologies. In the absence of these features, the diagnosis of an eating disorder
should be considered provisional, and other causes need to be thoroughly
evaluated (Devlin et al. 2011). Table 9–1 lists medical conditions to consider
in the differential diagnosis.

Medical Complications
Eating disorders have some serious medical complications, as discussed in this
section. The medical effects of individual eating disorder symptoms are listed
in Table 9–2.
150 Clinical Manual of Psychosomatic Medicine

Table 9–1. Medical differential diagnosis of eating disorders

System Diagnosis

Endocrine Diabetes mellitus, hyperthyroidism, Addison’s disease, Sheehan’s

syndrome (postpartum pituitary necrosis), panhypopituitarism
Gastrointestinal Malabsorption, pancreatitis, inflammatory bowel disease, peptic
ulcer disease, dysmotility disorders, superior mesenteric artery
syndrome, cystic fibrosis
Neurological Psychomotor or limbic seizures, neurodegenerative disorders,
hypothalamic or diencephalic tumor
Other medical Malignancies (especially lymphomas and gastrointestinal cancers),
collagen vascular disorders, human immunodeficiency virus,
parasitic infections, chronic renal failure, drug-induced weight
change

Source. Adapted from Devlin et al. 2011.

Osteopenia
Osteopenia is one of the most severe complications of anorexia nervosa and is
difficult to reverse. The risk for fractures later in life is increased (Lucas et al.
1999). Treatment recommendations include weight gain, 1,200–1,500 mg/
day of elemental calcium, a multivitamin with vitamin D, and individual as-
sessments for estrogen/progestin replacement.

Cardiac Changes
Congestive heart failure, pericardial effusions, bradycardia, and conduction
abnormalities with arrhythmias or prolonged QTc interval can occur in pa-
tients who are undernourished (Cooke et al. 1994). Prolongation of the QTc
is often associated with hypokalemia, hypomagnesemia, or hypocalcemia and
may be exacerbated by medications. Syrup of ipecac used to induce vomiting
may cause muscle damage, including cardiotoxicity with manifestations of
bradycardia, hypotension, and conduction defects.

Endocrine Changes
Reduced metabolic rate due to starvation results in a change in thyroid hormone
synthesis, including normal thyroid-stimulating hormone level, low or normal
 Eating Disorders 151

Table 9–2. Eating disorder symptoms and medical effects

System Medical effect

Restrictive eating Cognitive dysfunction, fatigue, cold intolerance,

constipation, dizziness, hypoglycemia, acrocyanosis,
orthostatic pulse and blood pressure, edema,
amenorrhea
Vomiting Dehydration, metabolic alkalosis, hypokalemia,
arrhythmias, esophagitis/gastritis, esophageal tears,
dental caries, parotid/submandibular gland
hypertrophy, gastroesophageal reflux disease,
pharyngitis
Binge eating/overeating Obesity, dyslipidemia, hypertension, type 2 diabetes
with weight gain mellitus, coronary artery disease, stroke, gallbladder
disease, osteoarthritis, sleep apnea, respiratory
disorders
Laxative abuse Cathartic colon, dehydration, hypokalemia,
metabolic acidosis or mild metabolic alkalosis
Diuretic abuse Dehydration, hypokalemia, hypomagnesemia
Appetite-suppressant abuse Hypertension, tremor, arrhythmias
Compulsive exercise Bradycardia, overuse syndrome, stress fractures
Water loading Hyponatremia, headache, nausea, dizziness, seizure

Source. Adapted from Devlin et al. 2011.

thyroxine (T4) and triiodothyronine (T3) concentrations, and elevated concen-

tration of reverse T3 (euthyroid sick syndrome). Other endocrine features that are
associated with starvation and that normalize with weight restoration include in-
creased cortisol and growth hormone levels, decreased estrogen, luteinizing hor-
mone, and follicle-stimulating hormone levels in women, and decreased testoster-
one level in men. In women with anorexia, amenorrhea is due to decreased
pulsatile secretion of gonadotropin-releasing hormone, and patients with bulimia
may develop amenorrhea without body weight changes (Devlin et al. 2011).

Electrolyte Imbalances and Nutritional Deficiencies

Eating disorder behaviors such as vomiting, diuretic or laxative abuse, and fluid
restriction may lead to severe dehydration with decreased potassium, magne-
152 Clinical Manual of Psychosomatic Medicine

sium, phosphate, sodium, and calcium levels. If hypokalemia is chronic, it may

lead to nephropathy and renal failure (Devlin et al. 2011). Deficiencies in thia-
mine among patients with anorexia can be associated with adult beriberi or
Wernicke-Korsakoff syndrome.

Concurrent General Medical Conditions

Eating Disorders and Diabetes Mellitus
Data are conflicting about the frequency of eating disorders in patients with in-
sulin-dependent diabetes mellitus, although high rates of intentional insulin
omission appear to occur in young women with type 1 diabetes for the purpose
of weight control. Blood glucose is elevated in these patients, and the risk of
ketoacidosis and other complications is increased (Crow et al. 1998). Patients
with binge-eating disorder may have an increased risk of metabolic syndrome
independent of the risk of obesity (Hudson et al. 2010). Among individuals
with type 2 diabetes who are overweight or obese and are binge eaters, the rate
of success with weight loss intervention programs appears to be similar to those
who are not binge eaters (Gorin et al. 2008).

Eating Disorders and Pregnancy

Infertility
One study found that 17% of women with infertility have an eating disorder
(Stewart et al. 1990). Long-term studies have shown no differences in cumu-
lative pregnancy rates in women with bulimia nervosa compared with those
who do not have an eating disorder (Crow et al. 2002), although women with
anorexia have more difficulty conceiving (European Society of Human Re-
production and Embryology [ESHRE] Capri Workshop Group 2006).

Pregnancy and Postpartum Period

The data are conflicting, but eating disorder symptoms often improve during
pregnancy and return during the postpartum period (Andersen and Ryan
2009). Patients who present with hyperemesis gravidarum should be assessed
for potential warning signs of an eating disorder, such as lack of weight gain
during the second trimester, abnormal body mass index, unexplained hyper-
kalemia from laxative use, or dental problems indicative of a long-standing
 Eating Disorders 153

history of frequent emesis. Compared to women without eating disorders,

women with eating disorders are more likely to have pregnancies complicated
by fetal growth restriction and preterm labor (Bansil et al. 2008). Pregnant
women with active eating disorders appear to be at elevated risk for delivery by
cesarean section and for postpartum depression (Franko et al. 2001), and
those with bulimia have an increased risk of miscarriage and preterm birth
(Morgan et al. 2006). Infant feeding may also be affected by eating disorders.
For example, infants of women with anorexia nervosa have a higher risk of
feeding difficulties between birth and 6 months (Micali et al. 2009). Mealtime
interactions have also been described as less positive and less interactive for
mothers with an eating disorder than for those without an eating disorder
(Waugh and Bulik 1999).

Treatments
Anorexia Nervosa
Inpatient Care
Weight restoration is the first treatment challenge for low-weight patients
with anorexia nervosa. The following criteria are suggested for determination
of inpatient psychiatric care (American Psychiatric Association 2006):

1. Severe malnutrition—less than 85% of ideal body weight or acute weight

decline with refusal to eat
2. Autonomic dysfunction—bradycardia (heart rate <40 beats/minute),
hypotension, or temperature dysregulation
3. Electrolyte abnormalities or glucose <60 mg/dL
4. Acute medical complication of malnutrition (e.g., pancreatitis, cardiovas-
cular compromise, delirium, seizures, syncope)

Refeeding Syndrome
When patients who are severely malnourished (i.e., less than 75% of ideal body
weight) are re-fed too rapidly, refeeding syndrome may occur. Refeeding syn-
drome is a potentially lethal condition resulting from rapid shifts in fluids and
electrolytes. The risk is particularly high with enteral and parenteral feeding,
but it can also occur with aggressive oral refeeding. Patients with chronic mal-
154 Clinical Manual of Psychosomatic Medicine

nutrition and those who have rapidly lost a substantial amount of weight are at
risk of this development during the first 2–3 weeks of refeeding. The cardinal
feature of the syndrome is severe hypophosphatemia with manifestations of
heart failure, rhabdomyolysis, seizures, and delirium. Other abnormalities in-
clude hypokalemia, hypomagnesemia, low glucose, hypocalcemia, and thia-
mine deficiency. Prevention of refeeding syndrome begins with identification of
high-risk patients. Vitamin supplements, including thiamine, should be started
immediately, and refeeding needs to be done slowly (e.g., 20 kcal/kg and in-
crease by 100–200 kcal/day). In addition to monitoring patients’ electrolytes
(phosphate, magnesium, and potassium), physicians need to observe patients
for signs of edema, congestive heart failure, and mental status changes (Amer-
ican Psychiatric Association 2006American Psychiatric Association 2000; Me-
hanna et al. 2008).

Pharmacological and Behavioral Interventions

Literature on behavioral and pharmacological interventions for anorexia ner-
vosa is scarce, and the results are inconclusive. Cognitive-behavioral therapy
(CBT) may decrease the likelihood of relapse for adults after weight restora-
tion, and family therapy is effective for adolescents but not adults (Bulik et al.
2007). Selective serotonin reuptake inhibitors (SSRIs) may be considered for
patients with depressive, anxiety, or obsessive-compulsive symptoms, but
studies have not shown an advantage in weight restoration. Second-genera-
tion antipsychotics, including olanzapine, quetiapine, and risperidone, are
used, but limited data are available regarding efficacy, and patient compliance
is a limiting factor.

Bulimia
Psychological Treatments
CBT for bulimia nervosa results in better patient outcomes than do minimal
treatment, supportive therapy, or purely behavioral interventions. The goal of
CBT is to address cognitive disturbances, such as overemphasis on weight and
shape, rigid rules about eating, and low self-esteem, in addition to the behav-
iors of purging and weight regulation. Interpersonal therapy (IPT) has also
 Eating Disorders 155

been shown to result in significant symptom change, although CBT may re-
sult in more rapid improvement (Agras et al. 2000).

Pharmacological Treatments
Antidepressants are more effective than placebo in treating bulimia, with the
most evidence supporting SSRIs. Fluoxetine at dosages of 60 mg/day or
higher has been found to improve outcome and decrease the likelihood of re-
lapse, although pharmacotherapy alone is not sufficient for long-term remis-
sion (Romano et al. 2002).

Binge-Eating Disorder
Psychological Treatments
Both CBT and IPT are effective treatments for binge eating, especially for pa-
tients with low self-esteem and high eating disorder psychopathology; rather
than weight reduction, the primary change is in reducing binge days and im-
proving psychological features. At 2-year follow-up, one study found that
guided self-help based on CBT and IPT resulted in greater remission than be-
havioral weight loss treatment. Findings on whether behavioral weight loss
treatment results in significant weight reduction have been inconsistent, al-
though obese individuals with binge-eating disorder appear to lose less weight
than obese patients without binge-eating disorder while undergoing behav-
ioral weight loss treatment (Wilfley et al. 2008; Wilson et al. 2010).

Pharmacological Treatments
Sibutramine, a serotonin-norepinephrine reuptake inhibitor, has been approved
by the U.S. Food and Drug Administration for the long-term treatment of obesity,
and some evidence supports its efficacy in the treatment of obese patients with
binge-eating disorder (Appolinario et al. 2003; Wilfley et al. 2008). Topiramate
has also been found to be efficacious in the short-term treatment of binge-eating
disorder associated with obesity (McElroy et al. 2003).

Bariatric Surgery
Approximately 25% of patients seeking bariatric surgery have binge-eating
disorder. (For more information, see Chapter 16, “Bariatric Surgery.”)
156 Clinical Manual of Psychosomatic Medicine

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1488, 2005
 10
Mood Disorders

Depression
Epidemiology of Depression
Prevalence
General population. The lifetime prevalence of major depressive disorder
(MDD) in the general U.S. adult population is 16% (Kessler et al. 2003). The
point prevalence rates are 2%–3% for men and 5%–9% for women.
Patients with chronic medical illnesses. Rates of depression are higher in
patients with chronic medical illnesses—such as diabetes mellitus, myocardial
infarction, HIV–related illness, cancer, stroke, Parkinson’s disease, and epi-
lepsy—than in those without medical conditions. The prevalence of depression
is estimated to be almost three times as high in patients with chronic disease as
in healthy control subjects (Egede 2007). The rates of depression appear to in-
crease progressively from community settings (3%–5%) to primary care set-
tings (5%–10%) to inpatient medical settings (10%–15%) (Katon 2003).

High Rates of Comorbid Psychiatric Disorders

The majority of patients (70%) with lifetime MDD have a comorbid anxiety dis-
order, substance use disorder, or impulse-control disorder (Kessler et al. 2003).

159
160 Clinical Manual of Psychosomatic Medicine

Worse Depression Outcomes in Medically Ill Patients

The mean duration of MDD in the general population is estimated to be
16 weeks (Kessler et al. 2003). Despite similar rates of treatment for depres-
sion, patients with comorbid medical illness have worse depression outcomes,
including increased likelihood of depressive symptoms at 6- and 12-month
follow-ups (Koike et al. 2002). In a study of medical inpatients, McKenzie et
al. (2010) found that depression persisted for at least 3 months after discharge
in 35%–50% of patients. Poorer physical and mental functioning during hos-
pitalization and a family history of depression were associated with persistence
of depressive symptoms.

Greater Functional Impairment

Nearly 60% of respondents in the National Comorbidity Survey Replication
described role impairment from depression as severe or very severe. Among in-
dividuals with chronic medical conditions, those with concurrent major de-
pression have higher degrees of functional disability and productivity losses
than do those without depression (Egede 2007). Several studies have sug-
gested that depression and anxiety are more predictive of functional impair-
ment over time than is the severity of physical illness (Mayou et al. 2000;
Sullivan et al. 1997, 2000). Functional impairment in elderly patients is a pre-
dictor of the development of major depression (Katon 2003).

Increased Medical Utilization and Costs

Substantially higher costs are associated with the medical care of patients with
depression than of those without depression. The cost is related to all types of
care, including primary care, specialty care, emergency department, and men-
tal health visits; pharmacy costs; diagnostic tests; and inpatient fees (Katon
2003). One study showed that total ambulatory and inpatient costs were
about 50% higher for depressed than nondepressed patients after adjustment
for chronic medical illness costs (Katon 2003; Katon et al. 2003).

Sociodemographic Characteristics
The factors associated with increased risk of major depression are similar in pa-
tients with and without chronic illness. These characteristics include female sex,
younger age (<65 years), lower income, higher body mass index, smoking, un-
employment, and declining health status (Egede 2007). Maladaptive coping
 Mood Disorders 161

styles also increase the risk of developing a mood disorder (Vinberg et al. 2010).
Factors that may influence the likelihood of depression in medically ill patients
include the physical effects of the illness and treatment, the personal meaning
associated with the medical condition, and the level of social support.

Relationship of Depression With Medical Outcomes

Complex Interrelationship
Not only does medical illness increase the likelihood of developing depression,
but the reverse is also true: depression may increase risk for medical illness such
as cardiovascular disease and stroke. The interplay among depression, risk fac-
tors for depression, and chronic medical illness is complex. Genetic vulnerabil-
ity, childhood adversity, and stressful life events are three known risk factors for
the development of major depression (Kendler et al. 2002). Childhood adver-
sity, including neglect and sexual abuse, may lead to maladaptive attachment,
which then may contribute to difficulty collaborating with physicians (Ciech-
anowski et al. 2001). Both childhood adversity and major depression are asso-
ciated with risk factors for medical illnesses such as smoking, obesity, and sed-
entary lifestyle. The symptom burden and functional impairment associated
with medical illnesses, in addition to the indirect pathophysiological effects
that medical illnesses have on the central nervous system (CNS) through in-
creased cytokine levels or other inflammatory factors, may contribute to the
development of depression. The negative impact of depression on patients’ col-
laboration with their physician and compliance with treatment, as well as the
direct pathophysiological effects of depression, increases morbidity and mor-
tality in patients with major depression and chronic medical illness (Katon
2003).

Higher Likelihood of Noncompliance With Medical Treatment

Compared with nondepressed patients, depressed patients are reported to be
three times more likely to be noncompliant with medical treatment. Having
positive beliefs and expectations regarding the effectiveness of medical treat-
ment improves compliance, and if a patient is hopeless due to depression, the
capacity to be optimistic is diminished. Social support is also important for
treatment adherence, and patients who are depressed may withdraw and isolate
themselves from their support network. If cognitive functioning is affected by
162 Clinical Manual of Psychosomatic Medicine

depression, the patient’s ability to remember and follow through with treat-
ment may be affected (DiMatteo et al. 2000).

Increased Mortality
The data have been mixed, but growing evidence supports an association be-
tween major depression (even subthreshold depression) and increased mortal-
ity. The relationship is most strongly established in patients with cardiovascu-
lar or cerebrovascular disease (Roose et al. 2001; von Ammon Cavanaugh et
al. 2001; Wulsin et al. 1999). In a prospective study of stroke patients, de-
pressed patients were three times more likely than nondepressed patients to
die during the 10-year follow-up (Morris et al. 1993). One study found that
in-hospital mortality of medical inpatients was predicted by the severity of
medical illness, a diagnosis of major depression based on modified criteria,
and a past history of depression (von Ammon Cavanaugh et al. 2001).

Higher Number of Unexplained Symptoms

Patients with depression have more medically unexplained symptoms, even
when controlling for severity of medical illness. In a study of patients with dia-
betes, cardiac disease, arthritis, and pulmonary disease, somatic symptoms
were as strongly associated with depression and anxiety as were objective phys-
iological measures (Katon et al. 2007).

Diagnosing Depression in Medically Ill Patients

Misinterpreting Depression as “Appropriate” Reaction
A common but misleading and potentially harmful approach is for physicians
to consider depression in medically ill patients to be an “appropriate” reaction;
this attitude trivializes the importance of depression and leads to undertreat-
ment. Sadness, however, is an expectable response to the many adverse effects
associated with medical illness (Cassem 1995).

Challenges of Making a Diagnosis

Historically, the issue of diagnosing major depression in medically ill patients has
been fraught with controversy for the following reasons (Li and Rodin 2011):

• At least four of the DSM-IV-TR (American Psychiatric Association 2000)

criterion A symptoms of major depressive disorder—fatigue, anorexia or
 Mood Disorders 163

weight loss, impairment in concentration, and sleep disturbance—can

also be accounted for by medical illness or medical treatment.
• Patients may present with anhedonia when physical symptoms such as pain
interfere with the capacity to experience pleasure in the absence of comor-
bid depression.
• Patients with advanced medical disease may report suicidal ideation or de-
sire for death in the absence of depressed mood.
• Depressive symptoms may manifest in atypical forms, such as noncompli-
ance with treatment or increased intensity of somatic symptoms.
• A new diagnosis of a medical problem or the progression of medical dis-
ease may be associated with intense feelings of loss and grief, and defining
the boundary between normal grief and depression can be difficult.

Diagnostic Approaches
Exclusive approach. Specificity is maximized by eliminating anorexia and
fatigue from the list of nine DSM-IV-TR criterion A symptoms of major de-
pressive episode (Table 10–1), and then requiring four of the remaining symp-
toms for a diagnosis. The method is more often used for research than for
clinical practice.
Etiological approach. The clinician makes a subjective judgment to deter-
mine whether a symptom should be attributed to depression or medical illness.
Substitutive approach. Physical symptoms are replaced by emotional symp-
toms. For example, low energy is replaced by brooding, self-pity, or pessimism,
and difficulty concentrating is replaced by nonreactive mood (Endicott 1984).
Inclusive approach. Symptoms of depression are taken at face value, with-
out exclusion or substitution due to comorbid medical issues. This is the most
sensitive approach and, given the generally favorable risk-benefit profile of
most antidepressants, is the most commonly applied approach at the clinical
bedside.

Demoralization
Demoralization has been described as a syndrome of hopelessness, loss of mean-
ing, and existential distress accompanied by a subjective sense of incompetence.
Patients may feel demoralized by disability, bodily disfigurement, dependency,
164 Clinical Manual of Psychosomatic Medicine

Table 10–1. DSM-IV-TR diagnostic criteria for major depressive

episode
A. Five (or more) of the following symptoms have been present during the same
2-week period and represent a change from previous functioning; at least one of
the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
Note: Do not include symptoms that are clearly due to a general medical
condition, or mood-incongruent delusions or hallucinations.
(1) depressed mood most of the day, nearly every day, as indicated by either
subjective report (e.g., feels sad or empty) or observation made by others
(e.g., appears tearful). Note: In children and adolescents, can be irritable
mood.
(2) markedly diminished interest or pleasure in all, or almost all, activities most
of the day, nearly every day (as indicated by either subjective account or
observation made by others)
(3) significant weight loss when not dieting or weight gain (e.g., a change of
more than 5% of body weight in a month), or decrease or increase in
appetite nearly every day. Note: In children, consider failure to make
expected weight gains.
(4) insomnia or hypersomnia nearly every day
(5) psychomotor agitation or retardation nearly every day (observable by
others, not merely subjective feelings of restlessness or being slowed down)
(6) fatigue or loss of energy nearly every day
(7) feelings of worthlessness or excessive or inappropriate guilt (which may be
delusional) nearly every day (not merely self-reproach or guilt about being
sick)
(8) diminished ability to think or concentrate, or indecisiveness, nearly every
day (either by subjective account or as observed by others)
(9) recurrent thoughts of death (not just fear of dying), recurrent suicidal
ideation without a specific plan, or a suicide attempt or a specific plan for
committing suicide
B. The symptoms do not meet criteria for a mixed episode (see DSM-IV-TR, p. 365)
C. The symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
 Mood Disorders 165

Table 10–1. DSM-IV-TR diagnostic criteria for major depressive

episode (continued)
D. The symptoms are not due to the direct physiological effects of a substance
(e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypo-
thyroidism).
E. The symptoms are not better accounted for by bereavement, i.e., after the loss of
a loved one, the symptoms persist for longer than 2 months or are characterized
by marked functional impairment, morbid preoccupation with worthlessness,
suicidal ideation, psychotic symptoms, or psychomotor retardation.

Source. Reprinted from American Psychiatric Association: Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association,
2000, p. 356. Used with permission.

feelings of being a burden on others, and fear of loss of dignity (Cockram et al.
2009; Kissane et al. 2001). Debate is ongoing as to whether demoralization rep-
resents a disorder or a normal reaction to overwhelming circumstances. The
prevalence of demoralization in medically ill patients has been estimated to be
30% (Mangelli et al. 2005). Jerome Frank (1974) described demoralization as a
characteristic of all conditions that respond to psychotherapy. The psychother-
apeutic approach with demoralized patients includes helping them mobilize
hope, self-agency, and connection with others (Griffith and Gaby 2005). (See
Chapter 15, “Psychosocial Management.”)

Depression Secondary to General Medical Condition

In the section on other mood disorders, DSM-IV-TR includes mood disorder
due to a general medical condition, which refers to mood disorders judged to
be the direct physiological consequence of a specific medical illness. Condi-
tions such as pancreatic cancer, Parkinson’s disease, multiple sclerosis, and hy-
pothyroidism are known to directly cause depression, but in many cases, a
causal relationship is difficult to confirm because other biological, psycholog-
ical, and social factors may also be contributing to the patient’s mood symp-
toms (Li and Rodin 2011). Table 10–2 lists medical conditions and toxic
agents associated with depression.
166 Clinical Manual of Psychosomatic Medicine

Table 10–2. Medical conditions and toxic agents associated with

secondary depressive disorders
Endocrine disorders Miscellaneous
Addison’s disease Alcoholism
Cushing’s disease Anemia
Hypopituitarism Heavy metal poisoning
Hypothyroidism Hypercalcemia
Infections Hypermagnesemia
Encephalitis Hypokalemia
Epstein-Barr virus Systemic lupus erythematosus
Hepatitis Neurological disorders
HIV Cerebrovascular disease
Pneumonia Dementia (particularly subcortical)
Postinfluenza Epilepsy (particularly with a temporal
Tertiary syphilis lobe focus)
Medications Huntington’s disease
Amphetamine withdrawal Multiple sclerosis
Antihypertensives: methyldopa, Parkinson’s disease
clonidine, guanethidine, reserpine Postconcussional disorder
Barbiturates Progressive supranuclear palsy
Benzodiazepines Sleep apnea
Cocaine withdrawal Stroke
Corticosteroids Subarachnoid hemorrhage
Opiates Tumors
Chemotherapeutic agents: vinblastine, Central nervous system
vincristine, procarbazine, L-asparaginase, Lung
interferon alfa Pancreas
Gonadotropin-releasing hormone
agonists
Interleukin
Interferon alfa-2
Mefloquine
Metoclopramide
Progesterone-releasing implanted
contraceptives
 Mood Disorders 167

Cognitive Changes Associated With Depression

Depression as a Neurodegenerative Disorder
A growing body of evidence suggests that depression, at least in some individ-
uals, is a neurodegenerative disorder (MacQueen et al. 2003). Young patients
who are depressed show deficits in executive function and memory, and such
deficits seem to worsen in older patients who are chronically depressed (Fos-
sati et al. 2002).

Correlation Between Depression Severity and Cognitive Performance

An association between depression severity and cognitive performance has
been demonstrated in the domains of episodic memory, executive function,
and processing speed, but not for semantic memory or visuospatial memory
(McDermott and Ebmeier 2009).

Involvement of Pathological Alterations of Limbic

and Cortical Structures in Depression
Decreased volumes of the hippocampus, basal ganglia, and orbitofrontal and
subgenual prefrontal cortex are found in patients who have had multiple epi-
sodes of MDD or longer illness duration. Gender, medication, stage of illness,
and family history all influence the nature of the findings in a regionally spe-
cific manner (Lorenzetti et al. 2009).

Differentiating Depression From Dementia

Distinguishing between early dementia and depression is often difficult, and
the two illnesses frequently coexist. Clinically helpful considerations are sum-
marized in Table 10–3.

Screening Instruments for Depression

Beck Depression Inventory–II
The Beck Depression Inventory–II (BDI-II) is a 21-item self-report scale that
has been well studied and widely used. Although several studies have found the
BDI-II to be an accurate measure of depressive symptoms, its utility in assess-
ing medically ill patients has been questioned because of the high proportion of
somatic items (Berard et al. 1998; Clarke et al. 1993; Wilhelm et al., 2004).
168 Clinical Manual of Psychosomatic Medicine

Table 10–3. Differentiating depression and dementia

Depression Dementia

Insidious onset Weeks to Months to years

months
Psychological distress present Yes Yes
Frequently answers “I don’t know” Yes No
Higher cortical function deficits (dysphasia, No Yes
dyspraxia)
Remote memory less impaired than recent memory No Yes
Inconsistent mental status examination findings on Yes No
repeated examinations
Past or family history of mood disorder Yes No
Awareness of cognitive deficits Yes No
Neuroimaging study results usually abnormal No Yes
Note. Depression and dementia can occur together, especially in subcortical dementias. When
a patient with dementia also has comorbid major depression, his or her cognitive deficits are
greatly magnified.

Center for Epidemiologic Studies Depression Scale

The Center for Epidemiologic Studies Depression Scale (CES-D) is a valuable
instrument in screening for depression in medically ill patients, although
some studies have found it to have a low positive predictive value (Pandya et
al. 2005; Thomas et al. 2001; van Wilgen et al. 2006). The CES-D is a 20-
item self-report measure in which only 4 of the items are somatic.

Hospital Anxiety and Depression Scale

The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-report scale
specifically designed for use with medically ill patients (Zigmond and Snaith
1983). It includes separate 7-item subscales for depression and anxiety; the depres-
sion subscale does not include somatic items and focuses on anhedonia. Studies
have supported the value of the HADS as a screening instrument for many differ-
ent medical populations (Bambauer et al. 2005; Herrmann 1997; Katz et al.
2004; Stafford et al. 2007; Walker et al. 2007), although it may not be a valid in-
strument for palliative care patients (Lloyd-Williams et al. 2001).
 Mood Disorders 169

Patient Health Questionnaire

The Patient Health Questionnaire (PHQ-9) is a self-administered diagnostic
instrument for depression. Each of the nine symptom categories in DSM-IV-
TR criterion A is scored from 0 (not at all) to 3 (nearly every day). The PHQ-9
is a commonly used instrument for depression screening in primary care clinics
and may be able to detect depression outcome and changes over time (Dejesus et
al. 2007; Kroenke et al. 2001; Lowe et al. 2004; Williams et al. 2005).

Very Brief Screening Instruments

Some studies suggest that a single-item screening question (e.g., “Are you de-
pressed?”) or a two-item subset of the PHQ-9 is as effective as the longer in-
struments (Chochinov et al. 1997; Lowe et al. 2005).

Pharmacological Management
Selective Serotonin Reuptake Inhibitors
Because of their tolerability and relative safety, selective serotonin reuptake in-
hibitors (SSRIs) are generally considered first-line treatment for depression in
medically ill patients. The success of the SSRIs in displacing the tricyclic anti-
depressants (TCAs) as first-line treatment is not due to efficacy but rather to
fewer anticholinergic and cardiac side effects and to greater safety in overdose.
Benefits. SSRIs may have benefits independent of effects on depression,
such as in the treatment of hot flashes in cancer patients (Kimmick et al.
2006) and global cognitive functioning in stroke patients (Jorge et al. 2010).
Adverse effects. Although SSRIs are generally well tolerated in depressed
medically ill patients, they do have some adverse effects (see also Chapter 14,
“Biological Treatments”).

• The most common side effects are gastrointestinal distress, nervousness,

sexual dysfunction, and insomnia.
• Anxiety and jitteriness may occur in at least 10% of patients, primarily
arising during early treatment and typically improving after the acute
phase. Short-term use of benzodiazepines may be helpful in alleviating
these symptoms. Nausea also occurs, most frequently in the early phase of
treatment. Other adverse effects include excessive sweating, headaches,
flushing, dry mouth, and appetite changes.
170 Clinical Manual of Psychosomatic Medicine

• Less common side effects of SSRIs, especially when taken with nonsteroi-
dal anti-inflammatory agents or warfarin, include the syndrome of inap-
propriate antidiuretic hormone, hyponatremia, and increased gastrointes-
tinal bleeding.
• During long-term treatment, weight gain, sleep disturbances, fatigue, ap-
athy, cognitive symptoms, and sexual dysfunction are possible side effects
(Smith et al. 2008).

Active metabolites and elimination half-life. SSRIs differ based on the pres-
ence of active metabolites and elimination half-life. For example, fluoxetine,
which has an elimination half-life of 1–3 days, is converted to norfluoxetine, a
potent SSRI with a half-life of 7–9 days. Therefore, steady-state plasma levels of
fluoxetine are not reached for 5–6 weeks; a similar length of time is required to
clear norfluoxetine after discontinuation. The longer half-life reduces the effect
of missed doses and mitigates the SSRI discontinuation syndrome. In contrast,
paroxetine has a short elimination half-life and is often associated with discon-
tinuation symptoms (Mann 2005).
Drug interactions. SSRIs differ in their risk for interactions with other
drugs. Citalopram, escitalopram, and sertraline are least likely to affect the
metabolism of other drugs, whereas fluoxetine, paroxetine, and especially flu-
voxamine are more likely to do so.

Serotonin-Norepinephrine Reuptake Inhibitors

• Venlafaxine blocks reuptake of serotonin at lower dosages and of norepi-

nephrine at higher dosages; its dual action at higher dosages, usually thought
to occur in the 150–225+ mg/day range, appears to benefit some patients
whose condition has not responded to SSRIs or other antidepressants, and is
effective in reducing the pain of diabetic neuropathy (Davis and Smith
1999). Venlafaxine reduces hot flashes in cancer patients (Loprinzi et al.
2000). The side-effect profile is similar to that of the SSRIs, except venlafax-
ine has the added potential of dose-related high blood pressure.
• Desvenlafaxine is the major active metabolite of venlafaxine. The most com-
mon side effects are nausea, dizziness, and insomnia (Rickels et al. 2010).
• Duloxetine, a newer dual agent, is approved for the treatment of diabetic
neuropathy and fibromyalgia in addition to depression. Unlike venlafax-
 Mood Disorders 171

ine, duloxetine does not appear to be associated with a significant risk of

elevated blood pressure.
• Milnacipran, the newest dual agent, has been approved by the U.S. Food
and Drug Administration (FDA) only for fibromyalgia, but the medication
has demonstrated efficacy and is marketed in Europe for the treatment of
depression. It is distinguished from the other serotonin-norepinephrine re-
uptake inhibitors (SNRIs) by its equipotent serotonin and norepinephrine
reuptake inhibition (Pae et al. 2009a) and the fact that cytochrome P450
enzymes are not involved in its metabolism. Dosing should be reduced in
the presence of renal failure.

Other Novel Antidepressants

• Bupropion, a norepinephrine-dopamine reuptake inhibitor, can be stimu-

lating, has minimal cardiac effects, rarely causes sexual dysfunction, and is
not associated with weight gain. However, bupropion may produce anxi-
ety, agitation, anxiety, and headache, and its use is avoided in patients with
seizures or at risk for seizures (e.g., patients with brain tumors).
• Mirtazapine, an α2-adrenergic receptor antagonist, is moderately anticho-
linergic and very antihistaminic; therefore, it promotes appetite, weight
gain, and sedation. Mirtazapine is well suited for certain patients (e.g., a
patient with advanced cancer who is depressed, cannot sleep, and has de-
creased appetite). Due to its serotonin type 3 receptor–blocking anti-
emetic effects, it may also be useful in patients who have nausea.
• Trazodone acts mainly postsynaptically as a serotonin type 2 receptor an-
tagonist. Its sedating properties and lack of anticholinergic side effects
contribute to its common use in lower dosages as a sleep aid. However, its
association with orthostatic hypotension, sedation, and priapism limits its
use in antidepressant dosages. Trazodone lacks the quinidine-like proper-
ties of the cyclic antidepressants but in rare cases has been associated with
cardiac arrhythmias.

Tricyclic Antidepressants
TCAs are still used in the hospital and clinic. They are effective for treating
chronic neuropathic pain, fibromyalgia, headache, insomnia, anxiety, and de-
pression.
172 Clinical Manual of Psychosomatic Medicine

Altered dosages. Lower dosages of TCAs are sometimes required for patients
with liver disease, patients who are elderly or malnourished, and patients taking
medications (e.g., paroxetine, fluoxetine) that can inhibit metabolism of
TCAs. Higher TCA dosages may be needed for patients taking medications
(e.g., carbamazepine, phenytoin, barbiturates) that induce hepatic enzymes.
Precautions. Prior to starting a TCA, a medical history should be performed
to determine whether the patient has cardiac conduction system disease. An
electrocardiogram (ECG) should be obtained if the patient has had cardiac dis-
ease or cardiac symptoms, and should be considered for patients ages 40 years
and older.
Adverse effects. At therapeutic levels, TCAs may produce sedation, ortho-
static hypotension, and anticholinergic effects, and may decrease the seizure
threshold. Like type Ia antiarrhythmic drugs (e.g., quinidine), TCAs may pro-
long ventricular depolarization and actually improve ventricular dysrhyth-
mias. However, a patient who has preexisting bundle branch disease is at risk
for second- or third-degree heart block. Conduction delay will appear on the
ECG as increased duration of the QTc, QRS, or PR intervals. When blood
levels are in the therapeutic range, TCAs have little if any effect on left ven-
tricular performance, even in patients with low ejection fractions. For patients
with a history of angina, an important consideration is that anticholinergic ef-
fects may increase the heart rate and slightly increase cardiac workload (Glass-
man and Bigger 1981).

Monoamine Oxidase Inhibitors

Indications and adverse effects. Despite their side-effect profile, dietary re-
strictions, and drug-drug interactions, monoamine oxidase inhibitors (MAOIs)
can be particularly useful agents for the treatment of anxiety and “atypical” de-
pression (e.g., depression with hyperphagia, hypersomnia, psychomotor slow-
ing, and rejection sensitivity) and can be effective in patients with treatment-
resistant depression (Pae et al. 2009b). MAOIs have potent hypotensive effects,
a fact that is particularly important when treating elderly patients, who may be
both more sensitive to orthostasis and more likely to fall and sustain fractures.
Other common side effects are dry mouth, gastrointestinal upset, urinary hesi-
tancy, sexual dysfunction, weight gain, myoclonic jerks, and headache.
 Mood Disorders 173

Mechanism of action. MAOIs irreversibly block monoamine oxidase

(MAO), the enzyme responsible for the oxidative deamination of neurotrans-
mitters such as serotonin, norepinephrine, and dopamine. The enzyme MAO
comes in two forms, MAO-A and MAO-B. The blockade of MAO-A in the
gastrointestinal tract is responsible for the severe hypertensive crisis that can
occur if patients ingest foods containing the sympathomimetic tyramine.
Tyramine is usually metabolized in the gastrointestinal tract, but the blockade
of MAO-A allows it to flow into the general circulation.
Oral and transdermal forms available. Phenelzine (45–90 mg/day) and
tranylcypromine (30–50 mg/day) irreversibly inhibit both MAO-A and MAO-
B. Selegiline at lower dosages is a selective irreversible inhibitor of MAO-B and is
indicated for the treatment of Parkinson’s disease. At higher dosages, it is a non-
selective inhibitor of MAO and functions as a traditional MAOI with antide-
pressant properties. A transdermal patch form of selegiline was approved by the
FDA in 2006 for use in the treatment of depression. No dietary restrictions are
necessary with transdermal selegiline when it is used at 6 mg/day because direct
inhibition of MAO-A in the gastrointestinal tract is bypassed. MAOI dietary re-
strictions are required if the 9-mg/day or 12-mg/day patch is used, because of
limited clinical and experimental experience with higher dosages (Patkar et al.
2006). Caution must be exercised when switching from an MAOI to another
antidepressant: a 2-week drug-free period is recommended to allow time for
MAO to regenerate. Fluoxetine, due to its longer half-life, requires a 5-week
drug-free interval.
Psychostimulants
Indications and administration. Psychostimulant medications, such as
methylphenidate (plasma half-life=1–2 hours) and dextroamphetamine (plasma
half-life = 6–8 hours), are an important treatment option in some situations (Ta-
ble 10–4). Psychostimulants are fast acting, well tolerated, and reasonably safe
among elderly and medically ill patients (Masand et al. 1991). Usual dosage
ranges are 5–20 mg/day for both methylphenidate and dextroamphetamine.
Administration is typically divided into two doses per day, in the morning and at
noon or early afternoon, because of the short half-lives. Doses later than 3:00
P.M. should be avoided so that sleep is not disturbed. When effective, the onset
of action is usually within 2–3 days.
174 Clinical Manual of Psychosomatic Medicine

Table 10–4. Clinical situations in which psychostimulants are an

important treatment option
When neurovegetative features of depression threaten health or life and a rapid
response is needed
In terminally ill patients with profound psychomotor retardation
For treatment-resistant depression
For adult attention-deficit disorder
For late-stage HIV disease (AIDS)–associated secondary mood disorders
For poststroke depression
For depression associated with subcortical dementias (e.g., dementia associated with
Parkinson’s disease)

Adverse effects. Adverse effects are relatively few but may include sinus
tachycardia, dysrhythmias, blood pressure elevation, psychosis, insomnia, an-
orexia, and exacerbation of spasticity in patients with upper motor neuron dis-
ease. These side effects usually occur at dosages much higher than those rec-
ommended. Stimulants are contraindicated in patients with structural heart
disease or tachyarrhythmia. Although some physicians are reluctant to pre-
scribe psychostimulants because of their abuse potential, the risk is low in pa-
tients without a substance abuse history at the dosages recommended for use in
the medical setting.

Commonly Used Augmentation Strategies

Commonly used augmentation strategies that have proved effective for depres-
sion include bupropion, buspirone, lithium, mirtazapine, and thyroid supple-
mentation with triiodothyronine or liothyronine (T3). Evidence is accumulat-
ing that atypical antipsychotics can also be useful adjunctive treatments for
treatment-resistant depression, although data are lacking regarding the efficacy
of atypical antipsychotics compared with other augmenting agents. Although
aripiprazole was approved in 2007 and an olanzapine/fluoxetine combination
in 2009 for treatment-resistant depression, the risk of the long-term side effects
of atypical antipsychotics must be weighed against the benefits (DeBattista and
Hawkins 2009).
 Mood Disorders 175

Treatment Strategies and Outcomes

Remission Versus Response
The current standard goal of treatment is remission, or the absence of depres-
sive symptoms, often defined as a score of ≤7 on the 17-item Hamilton Rat-
ing Scale for Depression (Ham-D17) or a score of ≤5 on the Quick Inventory
of Depressive Symptomatology Self-Report (QIDS-SR). With a response to
treatment, usually defined as a 50% or greater reduction in baseline symp-
toms, a patient may subjectively feel better, but residual depressive symptoms
result in a higher risk of relapse, continued impairments, and increased use of
medical services (Doraiswamy et al. 2001).
Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study
Study goal. Remission was the goal in the STAR*D study.
Study design. The multicenter, prospective, sequentially randomized con-
trolled trial of outpatients with nonpsychotic unipolar depression was de-
signed to mimic real-world clinical decision making. The protocol allowed
patients to be randomized to available treatment options (switching agents,
augmentation, and cognitive therapy) based on patient preference.

• For all treatments, a move to the next step could occur whenever intoler-
able adverse affects were encountered or when the maximally tolerated
dosage did not result in meaningful symptom reduction in 6–8 weeks.
• Patients with significant comorbid medical problems were not excluded
unless the conditions contraindicated the use of the study’s medications
(average number of general medical conditions=3).
• More than 75% of the participants had recurrent depression, with a
15-year average duration of illness (Rush et al. 2009).

Remission rates and dosages. Remission rates and dosages were similar in
the primary care and psychiatry settings.
First-step treatment: citalopram. One-third of patients remitted in first-
step treatment with citalopram.

• Among the patients who remitted, 50% achieved remission within 6 weeks,
and a substantial number responded or remitted at or after 8 weeks.
176 Clinical Manual of Psychosomatic Medicine

• Greater medical comorbidity was associated with lower remission rates.

• Other factors associated with poor outcomes included minority status,
lower socioeconomic status, concurrent psychiatric disorders (especially
substance use and anxiety disorders), lower function and quality of life,
and longer index episodes.
• Higher remission rates occurred among participants who had higher levels
of education or income and who were Caucasian, female, and employed
(Trivedi et al. 2006).

Second-step treatment. Switching to within-class, out-of-class, or dual-

action agents led to similar remission rates. About one-fourth of patients re-
mitted when switched from citalopram to sertraline, bupropion sustained re-
lease (SR), or venlafaxine extended release (ER).

• Augmentation of citalopram had similar remission rates between bupro-

pion SR (39%) and buspirone (33%), although bupropion had greater
symptom reduction and tolerability.
• Augmentation of citalopram with cognitive therapy or switching to cog-
nitive therapy had similar remission rates (Trivedi et al. 2006).

Third-step treatment. No differences in remission were found between pa-

tients switched to mirtazapine (8%) and those switched to nortriptyline
(12%) (Fava et al. 2006). Likewise, no differences in remission were found for
augmentation with lithium (13%) or T3 (25%), although more participants
discontinued lithium due to adverse effects (Nierenberg et al. 2006).
Fourth-step treatment. Remission rates were similar for patients switched
to the MAOI tranylcypromine (14%) and those switched to venlafaxine ER
plus mirtazapine (16%). More adverse effects occurred with tranylcypromine.
The dropout rate was higher with tranylcypromine, and the symptom reduc-
tion was greater with venlafaxine ER plus mirtazapine (McGrath et al. 2006).
Implications for clinical practice. The STAR*D results indicate that in
treating patients with depression, clinicians should do the following (Rush et
al. 2009):
 Mood Disorders 177

1. Aim for remission rather than response (i.e., 50% reduction in symp-
toms) to minimize the risk of relapse.
2. Encourage patients to stay in treatment. Of participants who remained
for up to four treatment steps, 67% achieved remission.
3. Dose aggressively to maximize the chances of remission.
4. Because average time to remission was 5–6 weeks, wait 6–8 weeks before
determining that a treatment is ineffective.
5. If the patient is tolerating first-step monotherapy and is beginning to ex-
perience improvement, consider augmentation as a second step.
6. Prepare the patient for the possibility of two or more treatment attempts.
The number of steps necessary will likely increase with greater comorbid-
ity and chronicity.
7. Consider aggressive treatments, such as combination or augmentation
strategies, early during therapy to achieve remission as quickly as possible.

Comparative Efficacy and Tolerability Among

New-Generation Antidepressants
Many studies have compared the new-generation antidepressants (i.e., SSRIs,
SNRIs, bupropion, and mirtazapine). Generally, the efficacy is similar, and if a
difference has been found, it has been modest (Hansen et al. 2005; Papakostas
et al. 2007). One meta-analysis suggested that mirtazapine, escitalopram, ven-
lafaxine, and sertraline were more efficacious than duloxetine, fluoxetine, flu-
voxamine, and paroxetine, and that sertraline and escitalopram had the best tol-
erability (Cipriani et al. 2009). When balancing efficacy, acceptability, and drug
cost, Cipriani and colleagues suggested that sertraline may be the most appro-
priate first-line agent. These findings were based on only 8 weeks of treatment,
which is a significant limitation of the meta-analysis (Cipriani et al. 2009).

Depression Severity Associated With Antidepressant Drug Effects

A recent meta-analysis found that the benefit of antidepressant therapy over
placebo increases with severity of depression symptoms and, on average, may
be minimal for patients with mild to moderate symptoms. The benefit of
medications over placebo was substantial for patients with very severe depres-
sion (Fournier et al. 2010).
178 Clinical Manual of Psychosomatic Medicine

Electroconvulsive Therapy
Electroconvulsive therapy (ECT) is a highly effective treatment for severe de-
pression with functional impairment, psychotic depression, and catatonia.
(See Chapter 14, “Biological Treatments,” for information on ECT and two
other brain stimulation techniques: vagal nerve and deep brain stimulation.)
Psychological Interventions
General Issues
The psychiatric examination is not complete without an attempt by the psy-
chiatric consultant to understand the meaning of the illness to the patient, in-
cluding the ways in which past experiences are affecting the patient’s current
approach to his or her illness. The value to the patient of “just talking” is often
underestimated. Because most hospital stays are short, brief therapies are used.
For patients seen in outpatient consultation, cognitive therapy, psychodynamic
psychotherapy, and supportive psychotherapy are available treatment options.
Group psychotherapy promotes support, improves interpersonal relationships,
models adaptive coping mechanisms, decreases loneliness, and helps the pa-
tient develop a sense of meaning in life. Cognitive therapy is particularly useful
for patients with false assumptions or beliefs about their illness, such as patients
who believe that illness represents punishment or weakness, who have unreal-
istic or distorted fears and expectations, and who have exaggerated or inappro-
priate responses to loss (Fava et al. 1988).
Efficacy of Psychological Interventions
Evidence indicates that cognitive therapy may be as effective as medication for
treating mild and moderate depression (DeRubeis et al. 1999). When psycholog-
ical treatment is combined with antidepressant therapy, patients experience higher
rates of improvement than with drug treatment alone (Pampallona et al. 2004). In
primary care clinics, psychological interventions are more effective for treating de-
pression than usual care alone in both the short term and the long term (Bortolotti
et al. 2008). (See also Chapter 15, “Psychosocial Management.”)

Bipolar Disorder and Secondary Mania

Epidemiology of Bipolar Disorder
The incidence and prevalence of mania due to a general medical condition are
unknown. Lifetime prevalence estimates for bipolar disorder are 1% for bipo-
 Mood Disorders 179

lar I, 1% for bipolar II, and 2% for subthreshold bipolar disorder (Merikangas
et al. 2007). Lifetime recurrence is frequent, and residual mood symptoms
early in recovery appear to be a powerful predictor of recurrence (Perlis et al.
2006b). Patients with residual affective symptoms develop a subsequent ma-
jor affective episode three times faster than patients who have an asymptom-
atic initial recovery (Judd et al. 2008).

Effects of Comorbid Bipolar Disorder and Medical Disease

on Medical and Psychiatric Outcomes
Studies suggest that medical comorbidity is associated with worse bipolar out-
comes (Pirraglia et al. 2009). The reverse relationship is also true: bipolar disor-
der predicts worse medical outcomes. Bipolar spectrum disorders are associated
with premature mortality due to general medical illness; compared with the gen-
eral population, patients with bipolar disorder have twice the risk of cardiovas-
cular mortality (Murray et al. 2009). Potential causes of premature mortality in-
clude adverse pharmacological effects, biological factors, health care disparities,
and poor lifestyle choices (Roshanaei-Moghaddam and Katon 2009). Modifi-
able risk factors, such as dyslipidemia, hyperglycemia, hypertension, smoking,
and obesity, are common in this population and contribute to illnesses such as
diabetes and coronary heart disease. Many psychotropic agents used in the treat-
ment of bipolar disorder have similar efficacy, but some are associated with more
metabolic side effects, a potentially important factor that deserves consideration
when choosing among these medications (Newcomer 2009).

Diagnosis
General Issues
Bipolar disorder is frequently unrecognized in patients who present with de-
pression, especially in the primary care setting; efforts to screen for both de-
pression and manic episodes can improve diagnosis and treatment (Das et al.
2005). In medically ill patients, mania can be confused with delirium because
abrupt onset, agitation, sleep disturbance, inattention, and psychosis can oc-
cur in both illnesses (Arora and Daughton 2007). Compared with patients
with MDD, patients with bipolar depression are more likely to have a family
history of bipolar disorder, an earlier age at onset, and a greater number of pre-
vious depressive episodes (Perlis et al. 2006a).
180 Clinical Manual of Psychosomatic Medicine

Diagnostic Criteria for Mania

The diagnostic criteria for manic episode (American Psychiatric Association
2000, p. 362) include the following:

1. The patient has had a distinct period of abnormally and persistently ele-
vated, expansive, or irritable mood, lasting at least 1 week (or any dura-
tion if hospitalization is necessary).
2. During the period of mood disturbance, at least three of the following
symptoms are present: inflated self-esteem or grandiosity, decreased need
for sleep, more talkative than usual, racing thoughts or flight of ideas, dis-
tractibility, increase in goal-directed activity, and excessive involvement in
pleasurable activities that have a high potential for painful consequences
(e.g., spending money, sexual indiscretion).
3. The mood disturbance leads to significant impairment in social or occu-
pational functioning.

Secondary Mania
According to DSM-IV-TR, secondary mania is diagnosed either as mood dis-
order due to general medical condition with manic features or as substance-
induced mood disorder with manic features. Secondary mania requires a
prominent and persistent elevated, expansive, or irritable mood, as well as evi-
dence from the history, physical examination, or laboratory findings that the
disturbance is the direct physiological consequence of a general medical con-
dition (American Psychiatric Association 2000). Secondary mania is not diag-
nosed if the mood disturbance occurs in the course of delirium.

Differentiation of Primary and Secondary Mania

A temporal correlation of the onset of mania and an organic factor helps to
differentiate primary from secondary mania. Secondary mania usually begins
hours or days after the physiological or toxic insult. Before mania can be as-
sumed to be due to an organic etiology, a careful history and examination are
necessary to determine whether a patient has had prior mood episodes (Arora
and Daughton 2007). Secondary mania can occur at any age, whereas primary
mania is more likely to occur in the first three decades of life. A family history
of bipolar disorder suggests but does not prove that mania is primary.
 Mood Disorders 181

Table 10–5. Selected causes of secondary mania

Neurological conditions Medications and substances
Frontotemporal dementia Alcohol
HIV encephalopathy Amantadine
Huntington’s disease Amphetamines
Multiple sclerosis Anabolic steroids
Psychomotor seizures Antidepressants
Stroke (temporal, right hemispheric) Cocaine
Traumatic brain injury Corticosteroids/corticosteroid withdrawal
Tumors Cyclobenzaprine
Viral encephalitis Dextromethorphan
Wilson’s disease Dopamine agonists (levodopa,
pramipexole)
Other systemic conditions
Hypericum perforatum (St. John’s wort)
Carcinoid
Isoniazid
Cushing’s syndrome
Methylphenidate and other stimulants
Hyperthyroidism
Modafinil
Niacin deficiency
Phencyclidine
Postoperative delirium
Procarbazine
Puerperal postpartum psychosis
Propafenone
Vitamin B12 deficiency
Sympathomimetic amines
(e.g., ephedrine)
Thyroid preparations
Zidovudine

Etiology of Secondary Mania

Table 10–5 lists potential causes of secondary mania. (For additional infor-
mation, see McDaniel and Sharma 2002.)
Neurological disorders. The presence of a neurological disorder is a signifi-
cant risk factor for secondary mania, particularly in patients who are elderly
(Shulman et al. 1992). Manic symptoms are associated with many neurological
disorders, such as some movement disorders, multiple sclerosis, head trauma,
stroke, CNS HIV infection, and epilepsy (Rundell and Wise 1989). The prev-
alence of mania in HIV-infected patients is estimated to be 4%–8% (Kil-
bourne et al. 2001). Evidence suggests that compared with HIV patients with
primary mania, HIV-infected patients with secondary mania are older, have
more severe cognitive impairment, and are more likely to have CD4 cell counts
182 Clinical Manual of Psychosomatic Medicine

below 350 cells/mm3. Manic symptoms in the secondary mania group are
more severe, with increased aggressiveness, paranoid delusions, auditory hallu-
cinations, and visual hallucinations (Nakimuli-Mpungu et al. 2006). Second-
ary mania is more likely to occur in patients with traumatic brain injury
(~10%) than in patients with other brain injuries, such as stroke (Jorge et al.
1993). Some studies have suggested an association with right-sided lesions in
patients with brain injury who develop secondary mania (Robinson et al.
1988; Starkstein et al. 1988).
Substance-induced mania. Corticosteroids and dopaminergic agonists are
frequent causes of medication-induced mania. Hypomania and mania are the
most common acute mood changes related to corticosteroid therapy (symp-
toms usually develop within 1 week), whereas depression occurs more often
with long-term corticosteroid therapy. Dosage is the most significant risk fac-
tor for the development of mood symptoms, and symptoms typically resolve
with dose reduction or discontinuation of corticosteroids. For patients with
psychosis or agitation, therefore, antipsychotics are considered the first-line
treatment (Warrington and Bostwick 2006).

Treatment of Bipolar Mania

General Considerations
The treatments for secondary and primary mania are similar, with two excep-
tions. First, in secondary mania, the etiological agent is identified and removed,
whenever possible. Patients might require surgical procedures to remove tumors,
medications to correct metabolic abnormalities, or removal of toxic agents asso-
ciated with secondary mania. Second, lithium is not usually a first-line treatment
for secondary mania because of increased side effects in patients who are medi-
cally ill, elderly, or both. However, there are exceptions: lithium has been used
successfully in treating mania secondary to corticosteroids and brain tumors
without seizures (McDaniel and Sharma 2002). Medication choice depends on
the acuity of presentation, underlying medical condition, route of administra-
tion, potential drug-drug interactions, and side-effect profile.

Lithium
Decreased suicide and all-cause mortality. According to findings from a
meta-analysis, lithium is effective in the prevention of suicide, deliberate self-
 Mood Disorders 183

harm, and death from all causes in patients with mood disorders (unipolar
depression, bipolar, schizoaffective disorder, and dysthymia) (Cipriani et al.
2005). For patients with bipolar disorder, lithium reduces the risk of relapse,
at least of manic episodes (Geddes et al. 2004).
Dosage and monitoring. Lithium is titrated within a rather narrow thera-
peutic range. Toxic effects occur at dosages only moderately higher than those
needed for therapeutic effects. Therefore, the clinician must monitor serum
lithium levels carefully; the levels are typically drawn 12 hours after the last
dose. Dosages should generally begin at 300 mg/day and be increased gradu-
ally to achieve serum lithium concentrations within the generally accepted
therapeutic range (0.6–1.2 mEq/L). Patients in an acute manic phase are best
treated with lithium dosages that achieve serum concentrations at the upper
end of this therapeutic range (0.8–1.2 mEq/L). However, for severely ill med-
ical patients, elderly patients, or patients with renal disease, lower dosages are
typically used. Steady-state serum levels typically take 5–8 days to achieve, and
clinical effects usually begin around 10–14 days. For this reason, concomitant
use of an antipsychotic or benzodiazepine (e.g., clonazepam) is often neces-
sary for acute control of agitation and psychosis. Evidence suggests that lith-
ium combined with risperidone or haloperidol is more effective than lithium
alone for treatment of acute mania (Sachs et al. 2002).
Adverse effects. In healthy individuals, the side effects of lithium are usually
mild, generally well tolerated, and often transient. The most common side ef-
fects are tremor, nausea, vomiting, diarrhea, polyuria, and polydipsia. Hypo-
thyroidism, rashes, nephrogenic diabetes insipidus, interstitial nephritis, and
weight gain are less frequent. Nonspecific ST segment and T-wave changes are
commonly seen on the ECG; conduction defects and arrhythmias are rare. Ap-
proximately 50% of patients taking lithium will have benign and reversible
T-wave flattenings (Cassem 2004). Before patients start taking lithium, the fol-
lowing should be considered: ECG, electrolyte measurements, thyroid func-
tion tests, weight measurements, and renal function tests, as well as pregnancy
tests in women of childbearing age. The concomitant use of nonsteroidal anti-
inflammatory drugs, thiazide diuretics, angiotensin-converting enzyme inhib-
itors, and cyclooxygenase-2 inhibitors may result in increased lithium levels.
Lithium toxicity markedly affects the CNS and can be a life-threatening emer-
gency. Symptoms of lithium-induced CNS toxicity include ataxia, slurred
184 Clinical Manual of Psychosomatic Medicine

speech, and nystagmus and can proceed to convulsions, coma, and death if
lithium levels are greater than 2.5 mEq/L. The threshold for more serious side
effects is lower in predisposed or medically ill patients. Dialysis is the treatment
of choice in cases of life-threatening lithium toxicity.

Anticonvulsant Mood Stabilizers

• Valproate has demonstrated efficacy for treatment of mania; there is also in-
creasing but limited evidence for an antidepressant effect in bipolar depres-
sion. The onset of antimanic activity generally occurs within several days to
2 weeks of achieving a serum valproate concentration of ≥50 mg/L (Malhi
et al. 2009). When valproate is prescribed for medically ill patients, the cli-
nician should be alert to gastrointestinal side effects, hepatotoxicity, coagu-
lation effects, and possible drug-drug interactions. Although hepatic tox-
icity is a concern when prescribing valproate, it is relatively rare. Hepatic
necrosis, a major risk factor for children younger than 2 years, is an uncom-
mon complication in adults taking valproate, occurring in 1 in 10,000 pa-
tients (Eadie et al. 1988).
• Carbamazepine has shown effectiveness in treating acute mania and may
also be effective for maintenance (Ceron-Litvoc et al. 2009), but its side-
effect profile has made it a less popular choice than valproic acid. When
prescribing carbamazepine to medically ill patients, a clinician must con-
sider its potential hematological toxicity, quinidine-like effects on cardiac
conduction, antidiuretic actions, and enzyme induction that can alter the
effects of other drugs. Toxic carbamazepine levels may occur when it is
given to a patient also taking the calcium channel blockers diltiazem and
verapamil (Stoudemire et al. 1993). Because carbamazepine is a potent in-
ducer of cytochrome P450 3A4, it influences the metabolism of many
drugs that rely on this enzyme; the blood levels of some drugs may de-
crease if carbamazepine is added to a patient’s medication regimen. Car-
bamazepine induces its own metabolism, necessitating gradual increases
in dosage over the first few weeks of treatment to maintain a steady blood
level.
• Lamotrigine has been shown in controlled studies to be effective for the re-
currence of bipolar depression, but it does not prevent mania (Bowden et
al. 2003; Calabrese et al. 2003). Although rash occurs in 10% of patients,
 Mood Disorders 185

the incidence of Stevens-Johnson syndrome is 0.08%, and the risk appears

to be minimized by a slow dose titration. The dosage of lamotrigine is gen-
erally doubled when combined with carbamazepine because of enzyme in-
duction; however, it is halved when used with valproate because of inhibi-
tion of metabolism. Other side effects include headache, blurred vision,
nausea, and vomiting.
• Despite their clinical use, gabapentin and topiramate have been found to
be no more effective than placebo (Malhi et al. 2009).

Antipsychotics
Antipsychotics are effective for acute mania, and several second-generation
antipsychotics have FDA approval for bipolar depression. The second-gener-
ation antipsychotics have efficacy similar to haloperidol for mania and are
comparable to treatment with a mood stabilizer. If an antipsychotic is required
for long-term therapy, the second-generation antipsychotics are most often
used due to decreased risk of extrapyramidal symptoms, although evidence is
emerging regarding the development of extrapyramidal symptoms associated
with these agents in patients with bipolar disorder. The addition of a second-
generation antipsychotic to a mood stabilizer appears to be better than treat-
ment with a mood stabilizer alone (Scherk et al. 2007).

Treatment of Bipolar Depression

Pharmacological Management
Treatment of bipolar depression is especially challenging. The use of antidepres-
sants has been controversial, and increasing data support the lack of efficacy of
antidepressants. In a large randomized controlled trial, the Systematic Treat-
ment Enhancement Program for Bipolar Disorder (STEP-BD), an antidepres-
sant (paroxetine or bupropion) or placebo was added to lithium or anticonvul-
sant treatment for patients with bipolar I or II disorder; neither antidepressant
was more effective than placebo (Sachs et al. 2007). TCAs and venlafaxine are
particularly associated with mood switching into mania, and bupropion is the
least likely to cause mood switch; the risk is reduced when antidepressants are
given in combination with a mood stabilizer (Leverich et al. 2006; Salvi et al.
2008). Randomized controlled trials of quetiapine and olanzapine (olanzapine
monotherapy and combination olanzapine/fluoxetine therapy) have demon-
186 Clinical Manual of Psychosomatic Medicine

strated efficacy for bipolar depression, with an onset of action in 1 week (Cruz
et al. 2010). One study showed improvement in depressive symptoms with ad-
junctive modafinil (Frye et al. 2007).

Psychological Interventions
In a group of patients with bipolar depression who did not receive benefit from
adjunctive antidepressant therapy in the STEP-BD study, cognitive-behavioral
therapy, interpersonal and social rhythms therapy, and family-focused therapy
were found to increase the likelihood of recovery, enhance interpersonal func-
tioning, and improve recovery speed (Miklowitz et al. 2007). For long-term
treatment, adjunctive psychotherapy improves symptomatic and functional
outcomes over 2-year periods (Miklowitz 2008).

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 11
Sleep Disorders

Insufficient sleep can result in fatigue, sleepiness, inattention, depressed

mood, and cognitive changes. Sleep disturbance may be an independent risk
factor for depression in older adults (Cho et al. 2008). Common medical
problems are associated with sleep abnormalities, and disruption of sleep may
worsen the subjective symptoms of the medical illness (Parish 2009). Sleep
disorders are categorized as sleep-related breathing disorders, hypersomnias of
central origin, circadian rhythm sleep disorders, parasomnias, and sleep-
related movement disorders.

Sleep Stages in Healthy Adults

Sleep can be subdivided into two general states: rapid eye movement sleep
(REM) and non–rapid eye movement sleep (NREM). The three main fea-
tures of REM sleep include increased electroencephalographic (EEG) fre-
quency, muscle atonia, and presence of rapid eye movements. NREM sleep
includes four stages; most time is spent in stage 2. Stages 3 and 4 are the deeper
stages of sleep known as delta-wave sleep, deep sleep, and slow-wave sleep. Pa-

195
196 Clinical Manual of Psychosomatic Medicine

tients with disrupted sleep often have decreased slow-wave and REM sleep
and spend more time than normal in stages 1 and 2 (Krahn 2011).

Sleep-Related Difficulties Associated

With Medical Problems
Sleep-related difficulties are frequently associated with common medical
problems. Patients with heart failure or chronic lung disease often have sleep
problems due to oxygen desaturation, paroxysmal nocturnal dyspnea, orthop-
nea, and coughing. Some patients with coronary artery disease experience
nocturnal angina. Poor sleep quality is associated with both obstructive and
restrictive lung diseases. Gastroesophageal reflux disease may result in diffi-
culty initiating and maintaining sleep, as well as increased nocturnal awaken-
ings (Parish 2009). Patients with renal disease have a high prevalence of sleep
disorders, including insomnia, restless legs, excessive daytime sleepiness, and
obstructive sleep apnea. About half of patients with end-stage renal disease re-
port excessive daytime sleepiness, and 20% of patients undergoing dialysis
have restless legs (Hanly 2004). Diabetes is associated with sleep-related com-
plaints, especially insomnia and excessive daytime sleepiness. In patients with
HIV infection, the severity of sleep problems appears to be correlated with the
stage of the disease (Darko et al. 1992). Disrupted sleep occurs in most pa-
tients with fibromyalgia, and the perception of pain is increased in patients
with poor sleep quality (Affleck et al. 1996). The prevalence of chronic in-
somnia in menopausal patients approaches 60%; vasomotor instability is a
primary cause (Ohayon 2006). Cancer patients undergoing treatment are
likely to have sleep problems, including excessive fatigue, insomnia, and day-
time somnolence. Even in healthy older adults with no subjective sleep com-
plaints, specific EEG sleep characteristics may predict increased risk of all-
cause mortality (Dew et al. 2003).

Evaluation of Sleep
History and Physical Examination
A detailed diagnostic history and a physical examination are necessary to dif-
ferentiate whether the patient’s symptoms are related primarily to a medical,
 Sleep Disorders 197

neurological, or psychiatric disorder; the patient’s environment; or both. Be-

cause patients may minimize the level of their daytime sleepiness, other infor-
mants such as family members are important in providing additional history.
Obtaining history from a bed partner is helpful, especially for information re-
garding sleep-related breathing and movement disorders. The Epworth Sleep-
iness Scale and the Stanford Sleepiness Scale are brief questionnaires that sub-
jectively quantify sleepiness. Areas of the physical examination that warrant
particular attention include the patient’s level of alertness, neck circumference,
body mass index, nasopharyngeal abnormalities, thyroid size, pulmonary and
cardiac findings, and cognitive changes. Screening laboratory tests to consider
include thyroid-stimulating hormone, ferritin, vitamin B12, folate, and com-
plete blood count (Krahn 2011).

Diagnostic Tests
Although polysomnography provides the best diagnostic accuracy in the eval-
uation of sleep disorders, it is not necessary when patients have certain disor-
ders, such as restless legs syndrome, or when the symptoms clearly represent a
specific disorder. Portable devices are available in some tertiary care hospitals.
Overnight pulse oximetry has limitations, including false negatives, but can
be beneficial in the medical setting in the initial evaluation of obstructive sleep
apnea. Used for the assessment of excessive daytime sleepiness, including nar-
colepsy, the Multiple Sleep Latency Test (MSLT) objectively measures a pa-
tient’s tendency to fall asleep (Krahn 2011). The Maintenance of Wakefulness
Test (MWT) is used to determine the outcome of treatment by measuring the
patient’s ability to stay awake.

Insomnia
Definition
Insomnia is present when all three of the following criteria are met (American
Academy of Sleep Medicine 2005):

1. The patient complains of difficulty initiating sleep, difficulty maintain-

ing sleep, or waking up too early. Alternatively, the patient complains that
sleep is chronically nonrestorative or poor in quality.
198 Clinical Manual of Psychosomatic Medicine

2. The difficulty occurs despite adequate opportunity and circumstances for

sleep.
3. The impaired sleep produces deficits in daytime function.

Epidemiology
Insomnia is one of the most common medical complaints. Each year, approx-
imately 30% of adults develop symptoms of insomnia and 7% develop an in-
somnia syndrome (LeBlanc et al. 2009). Prevalence is higher among elderly
people and occurs more often in women than men. More than half of elderly
people likely have at least one sleep complaint (Foley et al. 1995).

Causes of Insomnia
Medical, neurological, psychiatric, and environmental factors should be con-
sidered in the assessment of insomnia (Table 11–1). Medications that com-
monly contribute to insomnia, especially for elderly patients, include acetyl-
cholinesterase inhibitors, carbidopa-levodopa, corticosteroids, diuretics (which
cause nocturia), phenytoin, selective serotonin reuptake inhibitors, theophyl-
line, and beta-blockers. Caffeine can have a stimulant effect for 8–14 hours,
and caffeine clearance is reduced in patients with hepatic dysfunction. Alcohol
is often used by patients as a sleep aid but results in disrupted slow-wave sleep,
intense dreaming, and nocturnal awakenings (Wolkove et al. 2007).

Treatment of Insomnia
Factors that may cause or exacerbate insomnia should be addressed first, but
insomnia is often a primary rather than a secondary problem. Treatment ap-
proaches include improvement of sleep hygiene (Table 11–2), relaxation
training, stimulus control, sleep restriction therapy, cognitive-behavioral ther-
apy (CBT), and medications.

Nonpharmacological Strategies
Nonpharmacological strategies are effective in treating insomnia. Stimulus
control therapy targets the associations patients have with their bed and bed-
room, and their fears about not falling asleep. Patients often try to compensate
for lost sleep by staying in bed longer, which results in a circadian shift; sleep
restriction therapy increases the drive to sleep by decreasing the total time
 Sleep Disorders 199

Table 11–1. Selected causes of insomnia

Primarily medical Primarily environmental
Obstructive sleep apnea Community noise (traffic, alarms,
Angina neighbors)
Chronic obstructive pulmonary Hospital factors (blood draws, medication
disease administration, alarms, hospital staff )
Hypoglycemia Altered temperature
Asthma Primarily psychiatric
Congestive heart failure Psychophysiological insomnia
Gastroesophageal reflux Anxiety disorders
Hyperthyroidism Altered sleep-wake schedule
Acute and chronic pain Sleep state misperception
Medication induced Mood disorders (mania, depression)
Primarily neurological Withdrawal related
Central sleep apnea
Dementia
Restless legs syndrome

Source. Adapted from Krahn LE: “Sleep Disorders,” in The American Psychiatric Publishing
Textbook of Psychosomatic Medicine, 2nd Edition. Edited by Levenson JL. Washington, DC,
American Psychiatric Publishing, 2011, p. 338. Used with permission.

Table 11–2. Strategies for sleep hygiene

Sleep only as much as needed to feel rested
Avoid daytime naps
Exercise regularly, preferably at least 4 hours before bedtime
Avoid forcing sleep and go to bed when sleepy
Keep a regular sleep-wake cycle
Minimize caffeine
Avoid alcohol
Avoid nicotine especially prior to bedtime
Do not use the bedroom for activities other than sleep and sexual activity
Manage stress and avoid worrying in bed
200 Clinical Manual of Psychosomatic Medicine

spent in bed. CBT combines the previously described therapies and has been
found to be effective if used alone or in combination with pharmacotherapy
(Morin et al. 2009; Sivertsen et al. 2006). One study found CBT alone to be
superior to zopiclone alone in the treatment of acute and chronic insomnia in
older adults (Sivertsen et al. 2006). Combined CBT and pharmacotherapy for
the initial 6 weeks of treatment followed by CBT alone has been shown to
have the best long-term outcome (Morin et al. 2009). The medications most
commonly used include benzodiazepines, nonbenzodiazepine hypnotics, and
melatonin agonists (Table 11–3).

Benzodiazepines
Meta-analyses of randomized, placebo-controlled trials suggest that benzodi-
azepines and nonbenzodiazepine hypnotics decrease sleep latency and the
number of awakenings, thereby improving the quality and duration of sleep
(Buscemi et al. 2007). The primary difference between the benzodiazepines is
the duration of action, as outlined in Table 11–3. Their use is limited by ad-
verse effects, which include impaired memory, motor incoordination, seda-
tion, respiratory suppression, and dependence. Complex sleep-related behav-
iors may also occur, including driving, making telephone calls, and eating
while not fully awake. Elderly patients are at particular risk for delirium, agi-
tation, night wandering, and falls.

Nonbenzodiazepine Hypnotics
The nonbenzodiazepine hypnotics differ from the benzodiazepines in that
they have more selective effects on one γ-aminobutyric acid (GABA) type A
receptor. The selectivity also results in fewer anxiolytic and anticonvulsant ef-
fects. The adverse effects are similar to those of benzodiazepines but possibly
are less severe and less frequent.

Melatonin Agonists
Ramelteon, a melatonin agonist, provides most benefit for patients with sleep-
onset insomnia. It should be avoided in patients with hepatic dysfunction.
Rare side effects include headache, somnolence, and sore throat, but it is not
associated with dependence, withdrawal, or rebound insomnia (Griffiths and
Johnson 2005).
 Sleep Disorders 201

Table 11–3. Medications for treatment of insomnia

Drug Half-life (hours) Usual adult dose (mg)

Benzodiazepines
Triazolam 2–5 0.125–0.25
Oxazepam 5–10 15–30
Temazepam 8–12 15
Lorazepam 10–14 0.5–1
Clonazepam 18–50 0.25–0.5
Nonbenzodiazepines
Zaleplon 1 5–10
Zolpidem 1–3 5–10
Eszopiclone 6–9 1–3
Melatonin agonist
Ramelteon 1–5 8

Other Medications
Medications and over-the-counter products that have sedative properties but
have not been approved by the U.S. Food and Drug Administration for insom-
nia are frequently used for their sleep-promoting effects; these medications in-
clude antidepressants, antipsychotics, diphenhydramine, herbal products, and
melatonin. Trazodone is frequently used, but limited evidence is available to
support its use (Mendelson 2005). Doxepin and amitriptyline are the most se-
dating tricyclic antidepressants and may be helpful for patients with comorbid
insomnia and neuropathic pain, but they are associated with adverse effects, es-
pecially for patients who are medically ill. One study showed that in the treat-
ment of insomnia alone, low-dose doxepin was effective in elderly patients
(Scharf et al. 2008). Low-dose mirtazapine has antihistaminergic effects, but
other side effects including weight gain need to be considered. Quetiapine is
commonly used as a sleep aid; however, limited data support its use (Sateia
2009), and it is expensive. Some studies have shown quetiapine to be effica-
cious in patients with comorbid mood disorders or posttraumatic stress disor-
202 Clinical Manual of Psychosomatic Medicine

der (PTSD) (Endicott et al. 2007; Robert et al. 2005; Todder et al. 2006).
Diphenhydramine is generally not recommended because it may rapidly lose
its effectiveness, and anticholinergic side effects are problematic in patients
who are medically ill. Melatonin has not been found to be effective for primary
insomnia, but it may be beneficial for delayed sleep phase syndrome (Buscemi
et al. 2005).

Sleep-Related Breathing Disorders

Sleep-related breathing disorders are characterized by abnormal respiratory pat-
terns (e.g., apneas, hypopneas, or respiratory effort–related arousals) or abnor-
mal reductions in gas exchange (e.g., hypoventilation) during sleep. These
disorders are associated with significant morbidity and impairment, including
cardiovascular disease, impaired daytime functioning, and depression (Peppard
et al. 2006). Sleep-related breathing disorders include central sleep apnea, ob-
structive sleep apnea, and sleep-related hypoventilation/hypoxemic syndromes.

Central Sleep Apnea

Central sleep apnea is differentiated from obstructive sleep apnea by the
absence of snoring. Patients are often older, have cerebrovascular and cardio-
vascular disease, and present with insomnia rather than excessive daytime
sleepiness. Treatment can include hypnotics to decrease arousals, or supple-
mental oxygen (Krahn 2011).

Hypoventilation Syndromes
Patients with hypoventilation syndromes due to obesity or congenital abnor-
malities have mild hypercarbia and elevated serum bicarbonate while awake and
which worsen during sleep. Hypnotics should not be given to these patients.

Obstructive Sleep Apnea

Obstructive sleep apnea is the most common sleep-related breathing disorder;
mild symptoms occur in 20% of adults and moderate to severe symptoms in
approximately 7%. Medical sequelae include systemic hypertension, mild
pulmonary hypertension, cardiovascular morbidity, and cognitive impair-
ment. Obstructed breathing during sleep and excessive daytime sleepiness are
 Sleep Disorders 203

the cardinal features of the disorder. Signs of obstructed breathing include

snoring, restlessness, and resuscitative snorts. The diagnosis, which is con-
firmed by polysomnography, requires more than five episodes of apnea an
hour in addition to frequent arousals, oxygen desaturation due to apnea, or
bradytachycardia. Risk factors include obesity, craniofacial abnormalities, up-
per airway soft tissue abnormalities, and possibly heredity, smoking, diabetes,
and nasal congestion (Young et al. 2004). Positive airway pressure therapy is
first-line treatment, and other treatments include oral appliances or surgery.

Hypersomnias of Central Origin

Hypersomnias of central origin include narcolepsy (with or without cata-
plexy), idiopathic hypersomnia, and behaviorally induced insufficient sleep.
Narcolepsy is a condition that is often unrecognized, with an estimated prev-
alence of 0.06% (Silber et al. 2002). Elements of REM sleep intrude into
wakefulness, and the overall effect is excessive daytime sleepiness. Additional
features of narcolepsy include hypnagogic hallucinations, sleep paralysis, and
cataplexy. Questioning a patient’s history of emotionally triggered transient
weakness is helpful diagnostically, because cataplexy is unique to narcolepsy.
The etiology of narcolepsy includes the absence of the neuropeptide orexin,
genetic factors, and rare brain lesions. Behavioral modifications such as a reg-
ular sleep schedule, daytime naps, and avoidance of medications that disrupt
sleep can be beneficial. The mainstays of pharmacological treatment include
modafinil, methylphenidate, and amphetamines. Cataplexy is treated with
REM sleep–suppressing agents, such as venlafaxine, atomoxetine, fluoxetine,
and γ-hydroxybutyrate.

Circadian Rhythm Sleep Disorders

Circadian rhythm sleep disorders consist of jet lag type, shift work type, de-
layed sleep phase pattern, advanced sleep phase pattern, and irregular sleep-
wake pattern. Patients with prolonged stays in an intensive care unit are prone
to developing circadian rhythm disorders. Patients with delayed sleep phase
pattern have difficulty falling asleep at night and waking in the morning, as
well as associated daytime sleepiness that interferes with functioning. Ad-
204 Clinical Manual of Psychosomatic Medicine

vanced sleep phase pattern is less common and is characterized by habitually

early sleep and wake times that are at least several hours earlier than desired
times. Treatment approaches include chronotherapy, light therapy, and mela-
tonin (Lu and Zee 2006).

Parasomnias
Parasomnias are undesirable motor events or experiences (emotions, percep-
tions, dreams) that occur during entry to sleep, within sleep, or during arous-
als from sleep. The patient has no conscious awareness of the movements or
behaviors, but they can appear purposeful.

Non–Rapid Eye Movement–Related Parasomnias

NREM-related parasomnias include disorders of arousal such as sleepwalking,
sleep terrors, and confusional states.

Rapid Eye Movement–Related Parasomnias

Patients with REM sleep behavior disorder appear to be acting out their dreams
because they lack normal muscle atonia during REM sleep. REM sleep behav-
ior disorder is associated with Parkinson’s disease, multiple system atrophy, and
dementia with Lewy bodies, and most commonly occurs in elderly males. Ini-
tial treatment involves modification of the environment to reduce the likeli-
hood of injury, and clonazepam is considered the first-line pharmacotherapy.
For patients who are unable to tolerate clonazepam, melatonin is an alternative
(Gagnon et al. 2006).
A common REM disorder associated with psychiatric illness is nightmare
disorder, particularly in patients with PTSD. Prazosin has been shown to de-
crease PTSD-related nightmares (Dierks et al. 2007). Nonpharmacological
treatments, particularly imagery rehearsal therapy, reduce chronic nightmares
and improve sleep quality (Krakow et al. 2001).

Miscellaneous Parasomnias
Miscellaneous parasomnias not involving a specific stage of sleep can occur
from medication or substance use. The use of zolpidem has been associated
 Sleep Disorders 205

with complex behaviors such as sleepwalking, sleep-related eating, and sleep-

driving (Dolder and Nelson 2008).

Sleep-Related Movement Disorders

Restless legs syndrome (RLS) is characterized by an urge to move the legs, usu-
ally accompanied by uncomfortable sensations that occur during rest and are
relieved by movement. The sensation may be described by patients as creep-
ing, crawling, or pulling, and it is localized to deep structures rather than the
skin. The prevalence of clinically significant RLS is estimated to be 2.7%, and
RLS occurs more commonly in females (Allen et al. 2005). The cause of pri-
mary RLS is unknown, but studies suggest a genetic basis for the disorder
(Montplaisir et al. 1997). Secondary RLS can occur with iron deficiency, end-
stage renal disease, diabetes mellitus, multiple sclerosis, Parkinson’s disease,
pregnancy, and venous insufficiency. The majority of patients with RLS also
have periodic limb movement disorder (PLMD), which involves involuntary
jerking movements that occur during sleep and result in daytime sleepiness.
Medications and other substances, such as caffeine, nicotine, alcohol, dopa-
mine-blocking antiemetics, antidepressants, and antipsychotics, may exacer-
bate the symptoms. If a patient requires an antidepressant, bupropion has
been shown to reduce periodic limb movements in patients with depression
(Nofzinger et al. 2000). First-line treatment options for patients with periodic
limb movements include pramipexole, ropinirole, and carbidopa-levodopa
preparations. Benzodiazepines and gabapentin are alternatives, and low dos-
ages of low-potency opioids may also be effective (Silber et al. 2004).

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mares in sexual assault survivors with posttraumatic stress disorder: a randomized
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 12
Somatoform and
Related Disorders

P atients have expectations of their physicians. They think they can tell the
physician what is not right, and the physician can identify the problem, treat
it, and relieve any dysfunction, pain, or suffering. Physicians, in turn, harbor
their own expectations for patients who have physical complaints: “A patient
should complain in reasonable proportion to demonstrative pathology, report
physical distress in bodily terms and emotional distress in psychological terms,
and accept a doctor’s opinion and advice compliantly” (Lipowski 1988,
p. 1361). These expectations may align agreeably when patient and physician
are faced with a fractured radius, but they often diverge when the patient has
chronic or cryptic abdominal pain. More than 50% of the general population
experiences somatic complaints during any given week; however, physicians
cannot find a definitive medical cause in a comparable proportion of patients
with physical symptoms who present for medical care (Kellner 1985). These
patients commonly use medical resources frequently, are often dissatisfied
with the outcome, and may engender additional medical complications.

209
210 Clinical Manual of Psychosomatic Medicine

A Challenging Arena
Physicians are well trained to detect, measure, and manage pathology of the
body—that is, those anatomical and physiological perturbations that are ex-
posed to the five senses (e.g., wheezing, a thready pulse, icteric sclerae, the
fruity fragrance of ketosis) or to the technology of the laboratory. However,
pathology of emotion and behavior, or the mind and soul, often eludes objec-
tive metrics. Physicians are familiar with coronary artery occlusion that sets
the stage for oxygen demand to exceed supply, resulting in myocardial is-
chemia reflected in chest or jaw pain; if there is poor collateral flow and no
prompt lysis of the clot, myocardial infarction follows and congestive failure
may develop. In contrast, physicians do not typically think of medical illness
or interpersonal stressors as setting the stage for coping demands to exceed re-
sources, resulting in emotional ischemia reflected in dysphoria or heartache;
nor can physicians anticipate that if no emotional oxygen is forthcoming, the
patient may develop an infarction of identity followed by congestive despon-
dency.

Disease and Illness

Distinguishing between disease and illness is useful for consultation psychia-
trists (Eisenberg 1977). Disease involves objectively measurable anatomical
deformations and pathophysiological states. Illness involves those experiences,
behaviors, and functional changes associated with disease (or the patient’s per-
ception of disease), including the personal suffering, alienation, and debilita-
tion that shape a patient’s quality of life (Folks et al. 2000). In other words,
disease is a pathophysiological process that is often but not always associated
with documentable lesions, whereas illness also encompasses the patient’s re-
sponse to the disease. A patient can have a disease without illness or could have
illness behavior without known disease. Mismatches are common and are at
the root of many management problems. For example, a patient with hyper-
tension may experience no symptoms and therefore deny that he or she is ill;
nonadherence to treatment soon follows. In contrast, the patient with a so-
matoform spectrum disorder experiences illness without evidence of a disease,
or if evidence is present, the patient’s reaction extends beyond conventional
expectations.
 Somatoform and Related Disorders 211

Hybrid Pathology
When a physiological cause cannot be found for a symptom or when the phy-
sician thinks that a significant disparity exists between the patient’s subjective
complaints and the objective findings, psychiatric consultation may be re-
quested to confirm or exclude a so-called functional, psychogenic, or psycho-
somatic etiology. The amplification or magnification of somatic sensations
varies widely among patients. Moreover, patients with hypervigilant sensitiv-
ity who amplify somatic symptoms (i.e., somatizers) are a heterogeneous
group and defy simple categorization or explanation. Not all somatizers have
a somatoform disorder. This amplification process has both trait and state
characteristics and is influenced by multiple factors (Barsky et al. 1992),
which include the following:

• The patient’s cognition (information, beliefs, opinions, and attribution)

• Developmental history
• Context of the symptom (feedback from others and expectations)
• Cultural setting
• Amount of attention to the symptom (when attention is increased, the
symptom is amplified; when decreased, the symptom is diminished)
• Comorbid conditions (anxiety and depression commonly amplify symp-
toms)

Clues to Somatoform Spectrum Illness

Brodsky (1984) listed clues that suggest that a patient has a somatoform spec-
trum illness:

• Developmental associations may have included prominent somatic em-

phases.
• Somatoform language is used in the family of origin.
• Parents are demanding or unrewarding except when child is ill.
• Parental figure has suffered a significant illness.
• Coping mechanisms apart from illness behavior are absent or unacceptable.
• Disengagement from anger, aggression, or usual responsibilities is accom-
plished through somatic reactions.
212 Clinical Manual of Psychosomatic Medicine

Common Presentations
Patients with somatoform spectrum illness have the tendency to experience,
amplify, and communicate psychological and interpersonal distress in the
form of somatic suffering and medically unexplained symptoms (Abbey
2002). Most cases can be grouped into one of these categories:

• Medically unexplained symptoms—Somatic symptoms are not explained

after appropriate medical and psychiatric assessment. This absence of ex-
planation argues that idiopathic symptoms is a more accurate descriptor and
may portend a shift in future taxonomy.
• Somatic presentation of psychiatric disorder—Patients with psychiatric disor-
ders, especially depression and anxiety disorders, often present to primary care
physicians with somatic symptoms as a prominent part of the clinical picture.
• Somatoform disorders—Patients present with physical symptoms that suggest
a medical disorder, worry excessively about contracting a disease, or both;
however, no medical disorder exists, or if one exists, it cannot fully explain the
complaint(s). Despite medical evaluation and reassurance, the patient’s
bodily preoccupation and worry about medical illness continue. For many
patients with somatoform disorders, illness is a “way of life” (Ford 1983).
• Conversion disorders—Patients exhibit signs and/or symptoms of disease
and/or disability as an expression of internal conflict—that is, their psy-
chological dilemma is converted into somatic dysfunction. Both the con-
flict and the conversion are unconsciously driven and are therefore beyond
voluntary control.
• Factitious disorders—Patients are understood to deliberately induce signs
and/or symptoms of disease so as to elicit medical care, thereby answering
an unconscious longing to engage in the role of patient for whatever pur-
poses it may serve.

Inadequacy of Conventional Treatment

Conventional treatment of somatoform and related disorders falls short.
Fourteen common physical symptoms are responsible for almost half of all
primary care visits; over a 1-year follow-up period, many of these symptoms
prove to be benign and only 10%–15% are found to be caused by a persisting
 Somatoform and Related Disorders 213

organic illness (Katon and Walker 1998). Somatizing patients have higher av-
erage health care costs than do other patients: total charges are 9 times greater,
hospital charges 6 times greater, and physician services 14 times greater. So-
matizing patients spend up to 7 days per month sick in bed, compared with
the general population average of half a day (G.R. Smith et al. 1986).

High Viscosity Between Societal Mores

and Somatic Symptoms
Disability, formal or informal, attributed to a specific somatic complaint is
generally respected more readily than an emotional complaint. Children learn
that a stomachache is more likely to earn reprieve from school than is anxiety
over a bully; employees know that colleagues will be more forgiving of an ab-
sence occasioned by a migraine headache than by dysphoria over a romantic
loss; and patients understand that physicians attend to somatic symptoms and
respond with action but may grow weary of, or even put off, patients who
complain of vague malaise.

Current Nosology Deliberations

The diagnoses presently classified as somatoform or related disorders have
earned close scrutiny by researchers and work groups, inside and outside psy-
chiatry (Dimsdale and Creed 2009; R.C. Smith and Dwamena 2007; Voigt et
al. 2010). DSM-5, scheduled for publication in 2013, is likely to introduce
substantial changes in nomenclature (American Psychiatric Association
2010). The research cited in this volume is based on existing categories and di-
rects consideration along conventional, topical lines, avoiding the proposals
currently unfolding in the construction of DSM-5.

Comorbidities and Differential Diagnosis

Somatic complaints may be the foremost concern of patients presenting with
a wide range of psychiatric conditions. A psychiatric referral requesting con-
firmation of a somatoform spectrum diagnosis requires careful consideration
of alternate explanations and frequent comorbidities, as discussed in the fol-
lowing subsections.
214 Clinical Manual of Psychosomatic Medicine

Medical Disorders
The consultant’s first task is to remain alert for medical disorders. The patient’s
personality or exaggerated behavior may have decreased the primary physician’s
index of suspicion for a medical diagnosis and attenuated the preconsultation
workup. Thorough review of the medical record is a time-consuming but im-
perative task.

Cognitive Disorders
Patients with dementia, delirium, or other cognitive disorders may present
with increased physical complaints, particularly when anxious.

Adjustment Disorders
If the symptom occurs as a reaction to significant acute stress, it is often self-
limited. Identification of the stressor and its significance to the individual is
the first and most important step in planning treatment.

Anxiety Disorders
A high correlation exists between anxiety and the development of somatic
symptoms (Simon and VonKorff 1991). Patients with an anxiety disorder,
particularly panic disorder, are especially aware of bodily sensations.

Mood Disorders
Depressed patients often have multiple somatic concerns, including the
neurovegetative signs of depression, and other physical complaints. Hypo-
chondriacal preoccupation during depressive episodes increases with age
(Cassem and Barsky 1991).

Substance-Related Disorders
Patients with substance abuse, dependence, withdrawal, and the medical se-
quelae of chronic substance use are seen commonly in the general hospital.
These patients commonly report physical symptoms.

Psychotic Disorders
Patients who are actively psychotic may report bizarre physical symptoms.
The consultant must ensure that physical symptoms are not ignored simply
because the patient has a chronic psychotic disorder. On the other hand, pur-
 Somatoform and Related Disorders 215

suit of bizarre physical symptoms that are clearly secondary to psychosis is

unnecessary.

Delusional Disorders
The following are the most common somatic delusions (sometimes called
monosymptomatic hypochondriacal psychosis):

• Delusions of infestation (e.g., complaints of insects or foreign bodies on or

under the skin)
• Olfactory delusions (e.g., a complaint of a foul odor from skin, mouth,
rectum, or vagina)
• Body dysmorphia (i.e., the belief that one’s body or a body part is ugly or
misshapen; however, the majority of patients with body dysmorphic dis-
order are not delusional, as discussed in “Body Dysmorphic Disorder”
later in this chapter)

Personality Disorders
Histrionic and dependent personality disorders are more common among
women presenting with prominent somatic concerns. In men, antisocial per-
sonality disorder is more common among those who emphasize somatic com-
plaints without discernible medical or surgical pathology.

General Principles of Approach

The common feature shared by the somatoform spectrum disorders is the
presence of physical symptoms that suggest a medical condition but are not
fully explained by a medical condition or by the direct effects of a substance or
another mental disorder. Somatoform illness behavior involves an individual’s
conscious or unconscious use of the body or bodily symptoms for psycholog-
ical purposes or personal benefit. Nonetheless, somatoform illness is almost
never an ordinal either/or (i.e., all one or all the other) phenomenon and
therefore requires a methodical, comprehensive assessment (Folks et al. 2000).

Evaluation
Although the patient identified by primary care physicians or specialists as a
potential somatizer may not have a somatoform or other psychiatric disorder,
216 Clinical Manual of Psychosomatic Medicine

data gathering is similar to that in a typical psychiatric consultation. The con-

sultant should do the following:

1. Establish the medical context (Abbey 2002):

• Collaborate with referral sources to better understand the reason for
referral.
• Review the medical records before the interview.
2. Understand the patient. In addition to the patient’s historical account of
his or her symptoms, the psychiatrist is attentive to the following ques-
tions:
• What is the extent of the patient’s disease?
• What is the magnitude of his or her suffering?
• Are disease and illness proportional?
• Does the illness serve to resolve particular issues?
• How do collateral observers (e.g., family) perceive the patient?
3. Consider potential functions served unconsciously by the somatic symp-
toms. For example, the patient might be unconsciously doing any of the
following:
• Removing himself or herself from an overwhelming situation
• Gaining the sick role and meeting dependency needs
• Moderating systems problems (e.g., diverting family attention)
• Punishing himself or herself for perceived wrongdoing
• Masking expression of an unacceptable wish or impulse
• Identifying with an important figure in his or her life
• Communicating with the only vocabulary patient knows
4. Use suggested interview tips. Many evaluations for somatoform disorders
are single encounters. The interview necessarily becomes an important
diagnostic and therapeutic instrument: the psychiatrist’s approach to clar-
ifying a diagnosis can build an alliance and become a stepping-stone to
constructive intervention. “Acknowledging and witnessing the awfulness
of someone’s experience can be a powerful counter to both isolation and
confusion; task is inquiry, not exhortation” (Griffith and Gaby 2005).
• Address patient’s ambivalence about seeing a psychiatrist early.
• Take the patient’s symptoms seriously.
• Pay particular attention to the range and depth of emotional response
to issues raised during the examination, level of denial, meaning of
 Somatoform and Related Disorders 217

symptoms and normal test results to the patient, and evidence of un-
warranted hostility toward physicians.
• When appropriate, conduct limited, relevant portions of a physical
and neurological examination, which may improve patient alliance
(Abbey 2002).
• Reframe and educate when asked, “Is this physical or psychological?”
• Pay close attention to symptoms, but listen also for the unspoken (i.e.,
consider whether anything is conspicuous by its absence).
• Be respectfully curious about the patient’s life, looking for relational
gaps and/or a current dilemma.
• Sniff for a silver lining (e.g., say to the patient, “From what you have
described, I imagine you wouldn’t wish this on your worst enemy.
Even so, do you ever look back and see that it has somehow helped
you become a better person?”).
• Interview questions that often shed light include the following:
– How has this illness affected your life?” or “How would you have
been different if I had met you before these symptoms began?”
– “Who truly understands what you’re experiencing?”
– “Is there anyone in your family with similar struggles?”
– “How is your partner managing?”
– “Do you feel that your symptoms drive him away, or is he some-
one who is inspired to go the extra mile for you?”
– “Can he tell if you’re having a bad day just by looking at you?”
– If the patient identifies herself as religious, ask, “Does God have
some purpose in this suffering for you? Do you have any ideas
what that may be?”
5. Use collateral tools. The Minnesota Multiphasic Personality Inventory
(MMPI) is particularly useful for patients who may be malingering and/
or who have severe characterological problems.
6. Distinguish “normal” from “abnormal.” Illness behavior refers to the
manner in which individuals interpret their symptoms, take remedial ac-
tion, and use sources of help (Mechanic 1986). Abnormal illness behavior
is indicated by amplified, inappropriate, or maladaptive perception, eval-
uation, and reaction to one’s symptoms, particularly when this behavior
218 Clinical Manual of Psychosomatic Medicine

pattern persists despite a physician’s offering an accurate explanation of

the symptoms and an appropriate course of management. The following
clues often indicate an overvaluation of somatic symptoms:
• Symptom multiplicity, severity, and chronicity
• Difficulty coping: degree of role impairment
• Disease conviction: resistance to benign findings and reassurance
• Illness as a way of life: invalidism
• Maladaptive response to medical care
• Refractoriness to palliative, symptomatic treatment

Management
In managing patients with somatoform spectrum disorders, the consulting
psychiatrist should do the following:

1. Support a thorough workup and maintain humility.

2. Align yourself with the patient and invite him or her to join you in col-
laborative curiosity about the symptoms—their history, patterns, mean-
ing, and consequences.
3. Use analogies or stories to teach interaction of mind and body. After hear-
ing, for example, about some individuals with performance anxiety who
encounter increased gastrointestinal motility before a public presenta-
tion, most patients will understand the connection and even smile when
the psychiatrist shares the vignette and ends by asking, “Now is that di-
arrhea a physical problem or a psychological problem?”
4. Encourage a formulation that honors the unconscious and respects the
patient’s perseverance despite adversity. For example, when explaining
conversion symptoms, the consultant might comment, “I admire the cre-
ativity of your unconscious mind to find a way to balance these compet-
ing loyalties in a very difficult situation.”
5. Adopt care and palliation, rather than “cure,” as a goal.
6. Recognize and control one’s own negative reactions and countertransfer-
ence. Somatizing patients commonly evoke strong negative emotional re-
sponses in physicians that may interfere with optimal clinical care.
7. Insofar as possible, consolidate medical contact—that is, have as much
care as possible under the oversight of a single primary physician.
 Somatoform and Related Disorders 219

8. Regular appointments, irrespective of a patient’s symptoms, will decrease the

use of other health care services. Without this proactive arrangement, illness
behavior is reinforced because symptoms become the necessary prerequisite
for attention; the patient also learns that if symptoms abate, the physician’s
attention is turned elsewhere. By scheduling regular appointments, the phy-
sician uncouples the linkage between symptoms and attention.
9. Assiduously evaluate and treat comorbid psychiatric conditions, particu-
larly mood and anxiety disorders because these tend to exacerbate somatic
amplification.
10. Be alert for new medical problems, but use diagnostic tests for objective
changes only.
11. Maintain awareness of psychosocial context. The health care system may
be the organizing hub for the patient’s life. If possible, educate and per-
suade significant others in the patient’s life regarding the value of reward-
ing non-illness-related behaviors.
12. Anticipate the risk for prescription or over-the-counter drug abuse be-
cause these patients often seek the opinions of multiple physicians.
13. Minimize polypharmacy to reduce the risk of iatrogenic complications.
The process of tapering unnecessary medications (whose meaning is
likely far different for the patient) can be long and difficult, so taking
small, realistic steps increases the chance for success.
14. Gradually shift emphasis from listening to somatic language to encour-
aging translation to psychosocial stressors.
15. Anticipate extending time and patience in caring for the patient.
16. Understand that getting better and saying “Thank you” would threaten
the patient’s new relationship with the physician (this dynamic is similar
to the description in item 8 in this list).

Collateral Management Tools

Physical Reactivation and Physical Therapy
Although engaging patients with somatoform disorders in exercise is often dif-
ficult, once they become more active, they often find the activity pleasurable
and report feelings of accomplishment, reduced stress, and greater confidence
in their body. Physical therapy is helpful for patients with conversion disorder
and may be the only treatment required.
220 Clinical Manual of Psychosomatic Medicine

Relaxation Therapies, Biofeedback, Meditation, and Hypnotherapy

Patients with somatoform disorders may be helped by relaxation therapies,
biofeedback, meditation, and hypnotherapy. Relaxation therapies aim to
modulate somatic sensations and give patients a sense of self-empowerment.

Cognitive Therapy
Cognitive therapy is effective for some patients with somatization (Kronke and
Swindle 2000) and hypochondriasis (Barsky and Ahern 2004; Hiller et al. 2002)
and can reduce health care use (Hiller et al. 2003). It is used in both individual
and group formats. A cognitive model directs attention to factors maintaining
preoccupation with worries about health, including attentional factors, avoidant
behaviors, beliefs, and misinterpretation of symptoms, signs, and medical com-
munications (Salkovskis 1989). Cognitive therapy is a valuable adjunctive man-
agement tool for pain disorders, helping the patient to identify and replace
distorted, negative attributions with more constructive coping strategies.

Group Psychotherapy
Group psychotherapy can provide gratification of social yearning, and the
need to somatize to establish or maintain relationships may be reduced (Ford
1984). A patient usually accepts confrontation regarding primary or second-
ary gain more easily from group members than from the individual’s therapist
(Abbey 2002). Dependency needs and anger at physicians or family are more
easily tolerated in the group setting, which tends to diffuse intense affects.
Many somatizers, however, will not attend group therapy.

Potential Consequences of Failure to Engage the Patient

When a psychiatrist fails to engage the patient constructively, the following
consequences are possible:

• Physician-patient conflict
• “Doctor shopping”
• Unnecessary diagnostic testing and treatment
• Iatrogenic side effects
• Excessive health care utilization
• Overlooking of new medical conditions
• Continued suffering because primary issues remain unrecognized
 Somatoform and Related Disorders 221

Somatization Disorder
Epidemiology
The general population lifetime prevalence of somatization disorder is estimated
at 0.1%–1.1%, depending on the criteria used (Karvonen et al. 2004; Regier et
al. 1988). The prevalence in medical settings is higher, up to 5% in some out-
patient primary care clinics (deGruy et al. 1987). Somatization disorder is more
common in lower socioeconomic strata and is perhaps 10 times more common
in women than in men. Symptom onset is usually during the teen years, often at
the time of menarche. Sexual or physical abuse, if not other markers of parental
neglect, is common among women with somatization (Waldinger et al. 2006).

Clinical Features
The typical patient with somatization disorder is a woman who began to ex-
perience medically unexplained symptoms in early adolescence and has, over
the years, continued to have repeated unexplained physical complaints involv-
ing multiple organ systems. According to DSM-IV-TR (American Psychiatric
Association 2000), the patient requires a history over several years of at least
four pain symptoms, two gastrointestinal symptoms, one sexual symptom, and
one pseudoneurological symptom, all unexplained medically and sufficient to
either impair function or warrant medical attention. Much more common
than those who meet full DSM criteria for the disorder are individuals with
multiple symptoms but not the minimum of eight necessary for diagnosis.

Associated Features
As high as 75% of patients with somatization disorder have comorbid Axis I
diagnoses (Katon et al. 1991), most commonly major depressive disorder, dys-
thymic disorder, panic disorder, simple phobia, or substance abuse. Up to
65% of patients with somatization disorder meet criteria for one or more per-
sonality disorders (Rost et al. 1992), most frequently avoidant, paranoid, ob-
sessive-compulsive, or histrionic.

Differential Diagnosis
Patients with uncommon medical syndromes, mysterious medical illnesses,
atypical presentations of common diseases, factitious disorder, or malingering
222 Clinical Manual of Psychosomatic Medicine

may all elicit consideration of somatization disorder. A detailed review of all

past medical records is key. Presence of the following raises the likelihood of a
somatization diagnosis:

1. A medical record best measured in pounds, or the electronic equivalent,

rather than pages
2. A lifelong history of medically unexplained symptoms
3. A long list of medication “allergies” and unusual reactions
4. Recurring stories of possible conversion symptoms
5. Vague, impressionistic, and often inconsistent or contradictory details
6. Like a greased pig at a county fair, a narrative that becomes more elusive
the more firmly a methodical physician attempts to lay hold of it
7. Despite prominent, prolonged complaints, a relative paucity of medical
comorbidity

Clinical Course and Prognosis

The psychiatric consultant first must ensure that patients receive an appropri-
ate diagnosis. Somatization disorder is a chronic but fluctuating disorder that
rarely remits completely; once established, this diagnosis influences how phy-
sicians and the medical system respond to a patient. These patients are at risk
for iatrogenic complications from numerous repetitive tests, procedures, and
medications; the cost of the disorder is staggering.

Management of Somatization Disorder

Appropriate management of somatization disorder is difficult to implement.
Most patients resist psychiatric consultation. The consultant must identify
and treat comorbid psychiatric conditions. Additional management recom-
mendations are largely identical to those discussed previously for the approach
to patients with somatoform spectrum disorders in general (see “General Prin-
ciples of Approach” earlier in chapter).

Undifferentiated Somatoform Disorder

Epidemiology
In the general population, 4%–11% of people have multiple medically unex-
plained symptoms consistent with a subsyndromal form of somatization dis-
order (Escobar et al. 1989). Further support for this diagnosis comes from the
 Somatoform and Related Disorders 223

study of distressed high utilizers of medical care, which has shown signifi-
cantly increased health care use by patients with functional somatic symptoms
who have too few symptoms to meet DSM-IV (American Psychiatric Associ-
ation 1994) criteria for somatization (e.g., Katon et al. 1991). These patients
far outnumber those who meet criteria for somatization disorder.

Clinical Features
Undifferentiated somatoform disorder is a residual diagnostic category for pa-
tients whose symptoms do not meet criteria for another somatoform disorder
but who nevertheless have significant dysfunction caused by unexplained
medical symptoms.

Differential Diagnosis
When a detailed review of a patient’s history and past medical records reveals
the characteristics of somatization disorder but the symptoms fall short of the
full criteria, undifferentiated somatoform disorder is a likely diagnosis. If one
or only a few medically unexplained symptoms have occurred, and especially
if the time course is brief, the consultant should look for an alternative diag-
nosis. The absence of a general medical diagnosis (by itself ) is not sufficient
evidence for a psychiatric diagnosis.

Clinical Course and Prognosis

Individuals with undifferentiated somatoform disorder are probably a heter-
ogeneous group and include those for whom an eventual diagnosis of a general
medical condition may explain their initial symptoms.

Management
Management of undifferentiated somatoform disorder is usually best served
by the same principles enumerated for somatoform patients in the earlier sec-
tion “General Principles of Approach.” For the consultation psychiatrist who
hopes to alleviate the intrusion of medically unexplained symptoms, it is use-
ful to remember the following (Maldonado 1999):

• The role or meaning of a symptom for a particular patient must be respected.

• A symptom whose psychological value or purpose has not been under-
stood will not be easily extinguished.
224 Clinical Manual of Psychosomatic Medicine

• The psychiatrist should beware of seeking to excise a symptom before pro-

viding the patient with a better defense.
• Patients will not give up a symptom until they believe they are strong
enough to do without it.
• Patients always do better when they have a powerful incentive for a symp-
tom-free state.
• The purpose of therapy is to enable patients to experience a healthy rela-
tionship that survives without reliance on somatic symptoms alone.

Hypochondriasis
Epidemiology
The prevalence of hypochondriasis depends on the diagnostic criteria used
(Barsky et al. 1986). A narrow definition estimates a 1%–3% rate of hypo-
chondriasis among various ethnic groups. Hypochondriasis is equally com-
mon in men and women. Onset typical occurs during early adulthood.

Clinical Features
The core feature of hypochondriasis is fear of disease or conviction that one
has a serious disease based on the misinterpretation of bodily symptoms, de-
spite normal physical examination findings and physician reassurance. Bodily
preoccupation (i.e., increased observation of and vigilance toward bodily sen-
sations) is common and lasts for 6 months or more. Patients with hypochon-
driasis believe that good health is a symptom-free state, and they are more
likely than control patients to believe that symptoms mean disease (Barsky et
al. 1992). “Concern about the feared illness often becomes a central feature of
the individual’s self-image, a topic of social discourse, and a response to life
stresses” (American Psychiatric Association 2000, p. 504). Central clinical fea-
tures of hypochondriasis are summed up by the four Ds:

• Disease conviction
• Disease fear
• Disease preoccupation
• Disability
 Somatoform and Related Disorders 225

Associated Features
Nearly 90% of the hypochondriacal patients in a general medical outpatient
clinic had one or more concurrent Axis I diagnoses; the most common were
generalized anxiety disorder (>70%), dysthymia and major depression (each
>40%), and somatization disorder (>20%) (Barsky et al. 1992). In keeping
with the prevalence of comorbid anxiety, individuals with hypochondriasis are
often obsessive in style, whereas somatizers are commonly highly expressive
and histrionic. Patients with hypochondriasis are high utilizers of medical ser-
vices and have the potential for iatrogenic complications from repeated inves-
tigations (Abbey 2002).

Differential Diagnosis
Hypochondriasis in a general medical setting is most often secondary to a
mood or anxiety disorder. The salient distinction between hypochondriasis
and a delusional disorder is that patients with hypochondriasis typically de-
scribe a perceived symptom that fuels their conviction or fear of a disease, and
the conviction is more pliable than in a delusional disorder.

Clinical Course and Prognosis

Hypochondriasis is typically a chronic condition that benefits little from hos-
pitalization, adding to the suggestion that it is better understood as a person-
ality style or an anxiety disorder (Barsky et al. 1992). Symptoms may improve
with resolution of underlying stressors, interpersonal conflicts, or mood and
anxiety disorders.

Treatment and Management

The psychiatric consultant should reassure patients regularly—even though re-
assurance usually does not change their behavior—and should protect them
from iatrogenic harm, especially nonindicated surgical procedures. Educating
family and significant others about the nature of hypochondriasis may help de-
crease anxiety and stress at home. Pharmacotherapy with a selective serotonin
reuptake inhibitor (SSRI) may be a useful adjunct for patients whose symp-
toms are especially obsessional (Fallon 2004). Compared with usual medical
226 Clinical Manual of Psychosomatic Medicine

care, brief cognitive-behavioral therapy has demonstrated clinically significant

improvement at 6- and 12-month follow-ups (Barsky and Ahern 2004).

Conversion Disorder
Epidemiology
The estimated prevalence of conversion disorder varies: 0.3% in the general
population, 1%–3% in medical outpatient settings, and 1%–4.5% in inpa-
tient neurological and medical settings (Toone 1990). Women outnumber
men with the disorder by a ratio varying from 2:1 to 10:1 (Murphy 1990).
Onset typically occurs during adolescence or early adulthood, although cases
can begin throughout the life cycle.

Clinical Features
Conversion disorder is a loss of or alteration in function that suggests a phys-
ical disease (usually neurological), although none can be established by usual
diagnostic means. The following are common presentations of conversion:

• Motor symptoms (e.g., paralysis, disturbances in coordination or balance,

localized weakness, akinesia, dyskinesia, aphonia, urinary retention)
• Sensory symptoms (e.g., blindness, double vision, anesthesia, paresthesia)
• Combined motor and sensory components, as with some epileptiform
events

The initiation or exacerbation of the symptom is associated with a stress

that is perceived as extreme by the patient, although this psychological threat
or dilemma is characteristically not consciously grasped. Conversion refers to
the unconscious transformation of intrapsychic conflict to a physical symp-
tom; this process is sometimes referred to as primary gain. Persons with a con-
version symptom frequently have a psychological “bind” as in the case that
follows.

Case example: A devoted father and Army Airborne paratrooper has devel-
oped paralysis of his right arm 2 weeks after a close buddy was killed in a train-
ing jump and 3 weeks before his second child is due. The conscientious
paratrooper is in a no-win bind: he is immobilized between the push of loyalty
 Somatoform and Related Disorders 227

to his comrades, duty to country, and machismo of his unit, and the conflict-
ing pull of his wife, his child(ren), and the fresh reminder that his work is dan-
gerous. Paralysis provides an honorable resolution, if temporary: his buddies
and commander are concerned for his medical welfare, and his wife is relieved
that he will not be sent to Central America for drug interdiction training as
had been planned.

Caveats
In considering whether a patient has conversion disorder, the consultant
should keep in mind the following caveats (Stone 2009, p. 181), which in fact
apply to the evaluation of all functional symptoms:

• Don’t believe all the physical diagnoses in the medical notes.

• Don’t wade in early with blunt questions about “depression” or “anxiety.”
• Don’t make a diagnosis of functional symptoms because someone has an
obvious psychiatric problem/personality disorder.
• Don’t avoid a diagnosis of a functional problem because someone seems
too “normal.”
• Don’t misinterpret “exaggeration to convince” as “exaggeration to deceive.”

Associated Features
Protracted conversion reactions are sometimes associated with secondary
physical changes (e.g., disuse atrophy). Patients frequently have a model for
the symptom in a family member or close friend. Individuals with psycho-
genic nonepileptic seizures (described in “Clinical Course and Prognosis” be-
low) have a comorbid seizure disorder in 10%–30% of cases; the range reflects
the stringency of diagnostic criteria for establishing a current seizure disorder
(Jones et al. 2010).

Differential Diagnosis
The pitfall in making a diagnosis of conversion disorder is the potential for a
later appearance of a medical disorder that, in retrospect, explains the so-
called conversion symptom. It is therefore imperative that positive presump-
tive evidence for conversion—that is, intrapsychic conflict or another stressor
associated with initiation or exacerbation of the symptom—exists prior to the
diagnosis. In follow-up studies, subsequent evidence of a disease process that
228 Clinical Manual of Psychosomatic Medicine

retrospectively explained the so-called conversion symptom was found in

about 5%–30% of cases, with the most recent studies suggesting that 5% is
the more accurate figure (Lazare 1981; Stone et al. 2003). The unconscious
nature of conversion helps distinguish it from the consciously planned ma-
nipulative behaviors associated with malingering and factitious disorders.

Clinical Course and Prognosis

Individual episodes of conversion typically have a sudden onset, are brief in
duration, and resolve when the associated psychosocial stressor (bind) remits
(American Psychiatric Association 2000; Murphy 1990). However, one fol-
low-up study found that >80% of the patients reported weakness and sensory
symptoms at intervals of 9–16 years after the initial occurrence (Stone et al.
2003).

Predisposing Factors for Conversion Disorder

The following factors have been reported as predisposing to conversion dis-
order (Toone 1990):

• Prior neurological disorders in the individual or in a close contact who

provides a model for the conversion symptoms
• Severe social stressors, including bereavement, rape, incest, warfare, and
other forms of psychosocial trauma

Improved Prognosis
A better prognosis for conversion disorder is linked to the following (Lazare
1981):

• Acute and recent onset

• Traumatic or stressful life event at onset
• Good premorbid health
• Absence of other major medical or psychiatric disorders

Psychogenic Nonepileptic Seizures

Jones et al. (2010) described the following long-term outcomes of patients
with psychogenic nonepileptic seizures:
 Somatoform and Related Disorders 229

• 90% reported continuing psychogenic nonepileptic seizure episodes

• 50% reported “current mental health problems” at 10-year follow-up
• 40% continued taking an antiepileptic drug
• Poor quality of life and poor overall levels of functioning

Treatment and Management

Many patients with conversion disorder are suggestible and will likely take to
heart a physician’s conclusion that gradual improvement can be expected.
Many patients show a rapid response to treatment, but some do not (Stone et
al. 2003). When a clear relationship between a conflict and a conversion symp-
tom is identified, short-term focused or supportive therapy is indicated. Direct
confrontation usually does not help and may worsen the symptom. Multidis-
ciplinary inpatient behavioral treatment was successful in 8 of 9 “acute” cases
but failed in 27 of 28 “chronic” cases; strategic-behavioral treatment (i.e., the
patient and patient’s family were told that full recovery constituted proof of an
organic etiology and that failure was proof of a psychiatric etiology) worked in
13 of 21 patients with chronic motor conversion disorder who had failed the
initial behavioral therapy (Shapiro and Teasell 2004). Pseudoseizures, tremor,
and amnesia are less likely to have a rapid, good outcome (Toone 1990).

Helpful Explanations for Patients With Functional Symptoms

Stone (2009) suggested that a clinician can do the following to help patients
with functional symptoms:

1. Explain what the patient does have: “You have functional weakness.”
2. Emphasize the mechanism rather than the cause: “Your nervous system is
not damaged but it is not functioning properly.”
3. Explain what the patient does not have: “You do not have [a stroke, mul-
tiple sclerosis, epilepsy, etc.].”
4. Express belief in the patient: “I do not think you are making up your
symptoms.”
5. Emphasize that the symptoms are common: “I have seen many patients
with similar symptoms.”
6. Emphasize reversibility: “Because there is no damage, you have the po-
tential to get better.”
230 Clinical Manual of Psychosomatic Medicine

7. Support expectation of resolution: “In my experience, many individuals

with symptoms like yours gradually improve.”
8. Emphasize that self-help is important: “These symptoms are not your
fault, but there are things you can do to help yourself get better.”
9. Use metaphors: “Think of your body as being a piano that is out of tune.”
10. Use written information: Provide a copy of the consult or other educational
literature that the patient can read and digest on his or her own schedule.

Adjunctive Tools

• Referral to a behaviorally based cognitive-behavioral program

• Physical therapy for reconditioning
• Medication, such as an antidepressant or an anxiolytic
• Continued education (e.g., referral of patient to www.neurosymptoms.org)

Body Dysmorphic Disorder

Epidemiology
Onset of body dysmorphic disorder (BDD) is typically during adolescence
(Phillips et al. 1993), although many years may pass before diagnosis because
of the patients’ reluctance to disclose symptoms. Prevalence rates vary from
1.8% in a population-based survey (Buhlmann et al. 2010) to 3.2% of psy-
chiatric patients (Zimmerman and Mattia 1998) and 10% of patients seeking
cosmetic surgery (Jakubietz et al. 2007).

Clinical Features
The hallmark of BDD is an obsession or preoccupation with an imagined de-
fect in appearance (or excessive concern with a slight physical anomaly) that is
accompanied by significant distress or impairment in social or occupational
functioning. The most common complaints involve facial appearance (e.g.,
wrinkles, nose, mouth), and less common complaints are about hair, breasts,
genitalia, or other body parts. Determining whether the patient’s complaint is
an overvalued idea or a somatic delusion is sometimes difficult (Hollander et
al. 1992).
 Somatoform and Related Disorders 231

Associated Features
Most patients with BDD have at least one comorbid Axis I psychiatric disor-
der (Gunstad and Phillips 2003). Common comorbidities include the follow-
ing (Grant et al. 2002, 2005; Phillips and Stout 2006):

• Mood disorders
• Substance use disorders
• Social phobia
• Obsessive-compulsive disorder
• Eating disorders

Psychosocial dysfunction due to shame over the imagined defect may be

profound. Patients may experience the following:

• Social withdrawal (up to 30% of patients with BDD are homebound for
periods of time)
• Broken relationships and lower likelihood of being married
• Impaired occupational capacity
• Referential thinking (i.e., attributing scrutinizing behavior to surround-
ing people)

Common idiosyncratic and often secretive behaviors include these:

• Fastidious grooming behavior

• Attempts to disguise or camouflage the perceived defect
• Avoidance of mirrors or frequent mirror checking
• Repetitive seeking of reassurance about appearance

Differential Diagnosis
Several Axis I disorders may share features with BDD. Salient distinctions in-
clude the following (Buhlmann et al. 2008):

• Major depression. Patients with comorbid major depression express depres-

sive symptoms that extend beyond the intense dysphoria that is primarily
associated with times when a patient is focused on appearance.
232 Clinical Manual of Psychosomatic Medicine

• Social phobia. Patients with social phobia fear negative evaluation by oth-
ers that is not limited to concerns about physical appearance and are less
likely to adopt ritualistic behaviors surrounding appearance in prepara-
tion for venturing out.
• Obsessive-compulsive disorder. Patients with obsessive-compulsive disorder
are less likely to experience obsessions and associated compulsive rituals
that are exclusively centered on physical appearance.
• Eating disorders. Patients with eating disorders experience disturbance of
body image, with frequent intrusive preoccupation and consequent ritu-
als, but these revolve around weight and shape concerns, whereas patients
with BDD typically have several areas of concern (e.g., hair, nose, skin).

Clinical Course and Prognosis

BDD is usually chronic, with few symptom-free intervals, although the inten-
sity of the symptoms often varies over time. Patients often suffer in isolation,
are unwilling to present for clinical attention due to embarrassment and
shame, and are unlikely to disclose their symptoms unless asked with a spec-
ificity that is informed by physician awareness of the disorder.
Serious sequelae are not rare (Buhlmann et al. 2008):

• Suicidal ideation—10 times higher rate than in general population (31%

vs. 3.5%)
• Suicide attempts—10 times higher rate than in general population (22%
vs. 2.1%)
• Cosmetic surgery—5 times higher rate than in general population (16%
vs. 3.0%)

Several factors are associated with lower likelihood of symptom remission

(Phillips et al. 2005):

• Severity of BDD (at intake for prospective study)

• Longer duration of BDD at intake
• Comorbid personality disorder

Factors that are not associated with symptom remission include the following
(Phillips et al. 2005):
 Somatoform and Related Disorders 233

• Gender, ethnicity, socioeconomic status

• Age at onset
• Delusionality of BDD symptoms
• Comorbid Axis I disorder

Treatment and Management

Surgical alteration of the perceived defect almost always offers only fleeting re-
lief and commonly becomes a source of dissatisfaction, new perceived defects,
and psychological destabilization; hostility and even violence against the sur-
geon may follow (Jakubietz et al. 2007). In contrast, SSRIs and cognitive-
behavioral therapy have proved efficacious (Bjornsson et al. 2010; Pavan et al.
2008).

Pain Disorder
Epidemiology
The prevalence of pain disorder is unknown, but the frequency with which
patients present at a consultation service with chronic pain, either in isolation
or associated with opiate dependence, is no surprise considering that it affects
over 50 million Americans (Turk and Wilson 2010).

Clinical Features
Psychological factors are important in the onset, exacerbation, or mainte-
nance of the pain, which is sufficiently severe to warrant medical attention or
interfere with function. Pain is neither intentionally produced nor contrived.
If a medical disorder is also present, psychological factors amplify the patient’s
experience of pain far beyond objective expectations based on known anat-
omy and physiology. Patients who qualified for the DSM forerunners (i.e.,
psychogenic or somatoform pain disorder) were described as having “the dis-
ease of the Ds” (Brena and Chapman 1983):

• Disability
• Disuse and degeneration of functional capacity secondary to pain behavior
• Drug misuse
• Doctor shopping
234 Clinical Manual of Psychosomatic Medicine

• Dependency (emotional)
• Demoralization
• Depression
• Dramatic accounts of illness

Associated Features
Depression, posttraumatic stress disorder, and panic disorder are diagnosed
frequently in patients with chronic pain syndromes (Sharp and Keefe 2005).
Up to 50% of individuals with chronic pain have depressive symptoms, and
25% meet criteria for major depression or an anxiety disorder. Several findings
regarding nonmalignant chronic pain and suicidal behavior are relevant for
the consultation psychiatrist (M.T. Smith et al. 2004):

1. Family history of suicide is strongly associated.

2. Pain in the abdomen versus other bodily locations is associated with a
fivefold increased risk of suicide.
3. Increased risk of suicide has no association with pain severity, pain dura-
tion, or comorbid depression.
4. Neuropathic pain is statistically protective against suicidality.

Differential Diagnosis
As with diagnosing conversion disorder, the most common pitfall in making a
diagnosis of pain disorder is the later appearance of a medical disorder that ex-
plains the pain. Therefore, the consultant should look for positive evidence of
somatoform contributions to the patient’s perception of pain (e.g., a relevant
conflict or stressor associated with initiation or exacerbation of pain).

Clinical Course and Prognosis

Long-term studies on outcomes of patients with pain disorder do not exist, but
the estimated cost in the United States of $100 billion annually in lost income
and productivity coupled with medical expense provides evidence of the substan-
tial morbidity of chronic pain (Stewart et al. 2003). Central nervous system plas-
ticity may contribute to further morbidity as neural pathways change, leading to
heightened pain sensitivity and a lowered pain threshold (Scholz and Woolf
2002). Iatrogenic complications are common and include opiate and benzodiaz-
epine dependence as well as unnecessary surgical interventions (Abbey 2002).
 Somatoform and Related Disorders 235

Treatment and Management

Treatment and management of pain syndromes are complex. When pain has
not yet become firmly entrenched in the patient’s experience, and particularly
if sensitive interviewing establishes a plausible functional role for the pain, the
patient may respond to an approach that parallels that described for conver-
sion disorder. When the pain is chronic and has become an organizing force in
the patient’s life, the following are the most effective strategies (Fishbain et al.
2004; Maizels and McCarberg 2005; Sharp and Keefe 2005):

1. Identify and aggressively treat psychiatric comorbidity.

2. Prescribe serotonin-norepinephrine reuptake inhibitors or tricyclic anti-
depressants.
3. Carefully weigh risks and benefits of adjunctive antiepileptics and atypical
antipsychotics.
4. Avoid narcotic analgesics if at all possible.
5. Refer the patient early to a multidisciplinary behaviorally based treatment
program.

Factitious Disorders
Epidemiology
Demographic analyses of patients with factitious disorders suggest two gen-
eral patterns. Patients with chronic factitious disorder (Munchausen syn-
drome) are usually middle-aged men who are typically unmarried and
estranged from their families. Patients with more acute forms of factitious dis-
order are usually women, ages 20–40, who have work experience in medical
occupations such as nursing and medical technology (Ford and Feldman
2002). Classically, Munchausen syndrome included not only chronicity of
symptoms but also pseudologia fantastica (telling tall tales) and peregrination
(wandering to multiple medical centers).

Clinical Features
Patients with factitious disorders intentionally feign, exaggerate, exacerbate,
or induce symptoms. These individuals are aware of their behaviors, although
their underlying motivations are understood to be unconscious. Factitious
236 Clinical Manual of Psychosomatic Medicine

disorder may occur with predominantly physical symptoms, predominantly

psychological symptoms, or combined physical and psychological symptoms.
In chronic factitious disorder, self-production of sometimes dramatic, often
cryptic, and potentially life-threatening illnesses allows the patient to achieve
the goal of assuming the sick role. In factitious disorder by proxy, signs and
symptoms are created in another person, usually a child or an elderly relative.
Although they have overlap, five levels of factitious disorder have been sug-
gested (Folks et al. 2000):

1. Fictitious history
2. Simulation
3. Exaggeration
4. Aggravation
5. Self-induced pathology

An alternative hierarchy, wherein each level tends to include the prior activi-
ties, is as follows:

1. Fictitious history
2. Feigned physical signs
3. Manipulation of diagnostic tests
4. Self-induced pathology

Differential Diagnosis
The diagnosis of factitious disorder with physical symptoms is difficult to
make, unless direct evidence is found (e.g., a syringe and insulin are found
hidden in the room of a hospitalized patient with unexplained episodes of
hypoglycemia). The diagnosis of factitious disorder with psychological symp-
toms is even more difficult to make, because no corresponding definitive lab-
oratory or other objective tests are available. Indirect evidence, such as no
medical diagnosis and a dramatic presentation, may cause frustrated medical
staff to request psychiatric consultation because they suspect factitious illness
or malingering. The psychiatric consultant must see past the staff ’s counter-
transference and look for positive evidence of a diagnosis. Some psychiatrists
use “unlikely,” “possible,” “probable,” or “definite” to indicate the likelihood
of the diagnosis.
 Somatoform and Related Disorders 237

Clinical Course and Prognosis

Factitious disorders are associated with considerable morbidity and mortality. Few
patients accept treatment, and even fewer achieve freedom from symptoms. If
confronted, some patients may deny but stop behavior, very few may acknowl-
edge behavior and enter treatment, and most will seek medical care elsewhere and
continue factitious behavior (Krahn et al. 2003; Wise and Ford 1999).

Treatment and Management

Recent changes in medical practice in the United States emphasize patients’ rights
and informed consent. As a result, practices such as clandestine searches of per-
sonal articles, although once commonplace, are now controversial. When a pa-
tient is suspected of having a factitious disorder, involvement of hospital
administration and advice from the hospital legal office may be necessary. What-
ever steps prove necessary, patient confidentiality must be maintained.

Malingering
Epidemiology
Malingering occurs when illness brings tangible gains. Malingering is most of-
ten encountered in prisons, courtrooms, and military settings (when disability
evaluations are performed) and among persons with addiction.

Clinical Features
Malingering is grossly exaggerating, lying, or faking physical or psychological
symptoms for the sole purpose of a concrete, recognizable gain (i.e., secondary
gain), as distinct from the unconscious benefit (i.e., primary gain) achieved by
conversion and factitious symptoms. Malingerers are motivated by specific ex-
ternal incentives, such as deferment from military service, avoidance of hazard-
ous work assignments, financial rewards such as disability payments, escape
from incarceration, or procurement of controlled substances (Ford and Feld-
man 2002). Vigilance for malingering is prudent if more than one of the fol-
lowing factors is present (McDermott and Feldman 2007; Slick et al. 2004):

• Antisocial personality disorder

• Lack of cooperation with psychiatric or medical evaluation and treatment
238 Clinical Manual of Psychosomatic Medicine

• Marked disparity between the claimed disability and objective findings

• Medicolegal presentation
• Notable psychosocial adversity without an apparent viable solution (e.g.,
homelessness and an estranged family, squandered friendships, and no shel-
ter vacancies)
• Opportunity for inflating compensation

Differential Diagnosis
Malingering is difficult to prove, unless direct evidence is found. The follow-
ing five conditions often require careful deliberation to distinguish them from
malingering (McDermott and Feldman 2007):

1. Undetected or underestimated physical illness. Malingering deserves serious

consideration before undertaking high-risk diagnostic procedures.
2. Pain disorder. The subjective nature of pain underscores the value of in-
conspicuous observation of the patient.
3. Somatization disorder. The range of complaints and involved systems may
be broader with somatization.
4. Hypochondriasis. These patients welcome diagnostic evaluations and are,
at least briefly, relieved by negative results.
5. Factitious disorder. Even noxious procedures may be welcomed because
they reinforce the sick role.

Course and Prognosis

Anxiety and depression may tilt a patient’s perception of his or her circum-
stances in life and contribute to an impulsive decision to malinger; such a pa-
tient may no longer need the benefits of malingering when the underlying
condition is treated. On the other hand, individuals with intrinsically poor
coping skills or those who stand to gain significant sums of money or other
compensation may prove disinterested in any effort to ameliorate their re-
ported symptoms.

Treatment and Management

Occasionally, when malingering is in the context of a hardy antisocial person-
ality disorder, confrontation may be appropriate. More commonly, down-
 Somatoform and Related Disorders 239

stream turbulence will be decreased by allowing the malingerer to save face

and by explaining that testing has not revealed a serious condition and that
further deterioration is not anticipated. Malingering may emerge as a legal
rather than a medical or psychiatric issue. With this in mind, the clinician
does well to substitute circumspection for frustration in his or her approach to
the patient. Each note should be written with the awareness that it could be-
come a courtroom exhibit (Ford and Feldman 2002).

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 13
Substance-Related Disorders

Consultation psychiatrists are in a unique position to identify and intervene in

substance-related disorders in medically ill patients. Current alcohol abuse or de-
pendence is present in up to 25% of general hospital patients (Curtis et al. 1989;
Gerke et al. 1997; Katz et al. 2008), and 20% of medical outpatients drink alco-
hol at unhealthy levels (Saitz 2005). Only 25% of individuals who develop sub-
stance use disorders seek any addiction treatment during their lifetime; of these,
fewer than half receive treatment from mental health professionals, whereas most
receive treatment from general medical providers (Schuckit 2009). A window of
opportunity may open for treating substance-related disorders in medical-surgi-
cal patients, because the patients’ resistance to treatment may weaken during
acute illness. The care of these patients benefits from collaboration between the
consultant and the referring physician. Often, the health care team has strong
feelings toward the substance-abusing patient, especially when intoxication or
overdose prompted the admission and when the team has cared for the patient
for substance-related medical problems in previous admissions. The consulting
team can support the primary team in the face of frustration with recidivist pa-
tients. Both teams must communicate to the patient the medical, psychological,
and social consequences of continued alcohol or drug use.

245
246 Clinical Manual of Psychosomatic Medicine

DSM Criteria
In DSM-IV-TR (American Psychiatric Association 2000), substance-related
disorders are divided into substance use disorders and substance-induced dis-
orders. Substance use disorders include alcohol and drug abuse and depen-
dence. Substance-induced disorders include intoxication; withdrawal; delir-
ium; dementia; sexual dysfunction; and amnestic, psychotic, mood, anxiety,
and sleep disorders. The loss of control over substance use has both neurobi-
ological and behavioral bases, both of which are modified over time as a result
of substance-induced changes in the brain (Self 2004).

Substance Abuse
Substance abuse is demonstrated by “a maladaptive pattern of substance use
leading to clinically significant impairment or distress, as manifested by one
(or more) of the following, occurring within a 12-month period” (American
Psychiatric Association 2000, p. 199):

1. Recurrent use resulting in failure to meet major obligations at work,

school, or home
2. Recurrent use in situations in which it is physically hazardous
3. Recurrent substance-related legal problems
4. Continued use despite recurrent social or interpersonal problems caused
or exacerbated by the effects of the substance

Substance Dependence
Dependence is demonstrated by “a maladaptive pattern of substance use, lead-
ing to clinically significant impairment or distress, as manifested by three (or
more) of the following, occurring at any time in the same 12-month period”
(American Psychiatric Association 2000, p. 197):

1. Tolerance
2. Withdrawal
3. Greater amounts or more prolonged use than initially intended
4. Persistent desire or unsuccessful efforts to cut down or control use
5. Considerable time spent obtaining, using, or recovering from use of sub-
stance
 Substance-Related Disorders 247

6. Sacrifice of important social, occupational, or recreational activities

7. Continued use despite awareness of adverse consequences

Alcohol
Alcohol is the most frequently abused substance. Two-thirds of Americans
drink; nearly 15% of men and 5% of women are heavy drinkers. About 25%
of men and women admitted to the hospital are heavy drinkers and are likely
to have an alcohol-related disorder (Seppa and Makela 1993; Yates 2002).
Lifetime prevalence of alcohol abuse among men is 15%, and alcohol depen-
dence is 10%; the rate is lower in women, but a higher percentage of women
than men seek help (Hasin et al. 2007). Alcohol-related problems usually be-
gin between ages 16 and 30; children of alcoholic parents have alcoholism
four to five times more often than do children of nonalcoholic parents.

Intoxication
Although multiple factors influence both the rate of absorption and eventual
blood alcohol concentration, a reasonable generalization is that 1 drink equiv-
alent (12 oz beer, 5 oz wine, 1.5 oz 80-proof whiskey) will yield a blood alcohol
concentration of 20 mg/dL, or 0.02%. In turn, the body metabolizes alcohol at
an approximate rate of 1–1.5 drink equivalents/hour once it has been ab-
sorbed. Unless the person is alcohol tolerant, mild euphoria occurs at blood
levels of 30–50 mg/dL, driving impairment is demonstrable at a level of 50 mg/
dL, and significant ataxia is present at 100 mg/dL. Disorientation and stupor
can occur at 200 mg/dL, and coma and death may occur in the alcohol-naïve
person at 400 mg/dL. In contrast, a chronic heavy drinker may develop suffi-
cient tolerance to allow a concentration of 500 mg/dL without the loss of abil-
ity to converse or appear grossly alert to the casual observer.

Recognition
Symptoms and signs of alcohol intoxication include the following:

• Alcohol odor (5% of alcohol is metabolized by the lungs)

• Disinhibition
• Mood lability
• Impaired judgment
248 Clinical Manual of Psychosomatic Medicine

• Ataxia
• Dysarthria
• Nystagmus

Management

1. Reduce stimulation by providing a quiet environment.

2. Impede absorption by offering food.
3. Alert security if the patient escalates in behavior.
4. If patient is severely agitated, sedate with lorazepam 1–2 mg intrave-
nously (iv) or intramuscularly (im) every hour as needed.
5. If lorazepam is insufficient, administer haloperidol 1–5 mg iv every hour
until calm.
6. Administer thiamine 100 mg im before dextrose-containing intravenous
fluids (many centers administer combined thiamine, folate, multivitamins,
magnesium, and phosphates intravenously in a variously named “goodie
bag”).
7. Thereafter, administer thiamine 100 mg daily and folate 1 mg daily.
8. Obtain a blood alcohol level and screen for other drug use.

Withdrawal
Withdrawal symptoms may appear within 6–48 hours after significant reduc-
tion in or cessation of prolonged alcohol use. Tremors typically peak 24–48
hours after the last drink and subside after 3–5 days of abstinence. However,
about 50% of alcohol-dependent individuals do not develop significant
symptoms of withdrawal (Schuckit 2006).

Recognition
Symptoms and signs of alcohol withdrawal include the following:

• Tremulousness
• Insomnia
• Irritability
• Nausea and diminished appetite
• Autonomic hyperactivity
• Anxiety
 Substance-Related Disorders 249

• Hypervigilance
• Mild transient illusions or hallucinations (even in the absence of other
stigmata of delirium)

Management
No single regimen will serve all patients equally well. Multiple protocols exist,
but the following fundamental elements are shared.
Medical support. Staff should monitor the patient’s vital signs; watch espe-
cially for hypertension and fever; and maintain hydration, but watch for fluid
and electrolyte imbalances, particularly hypoglycemia, hyponatremia, hy-
pokalemia, hypomagnesemia, and hypophosphatemia.
Pharmacological options. Pharmacological options serve the common
goals of patient safety by reducing agitation, averting autonomic hyperactivity
and seizures, and avoiding exacerbation of concurrent medical issues. Benzo-
diazepines (BZDs) are the mainstay of alcohol withdrawal protocols (McKeon
et al. 2008). One structured detoxification regimen is chlordiazepoxide 50 mg
orally every 6 hours for four doses, then 25 mg every 6 hours for eight doses
(Franklin et al. 2002); this approach takes advantage of the long half-life of
chlordiazepoxide to create an autotapering effect. For the same reason, some
clinicians prefer phenobarbital because its very long half-life provides some
protection against withdrawal symptoms even if the patient leaves the hospital
before withdrawal has been completed. Alternate regimens utilize BZDs that
are metabolized by glucuronidation (e.g., lorazepam 2–4 mg every 6 hours or
oxazepam 15–45 mg every 6 hours), especially for patients with alcoholic liver
disease, because these medications present less risk of excessive buildup of
blood levels.
Inpatient versus outpatient treatment. Depending on the severity of
symptoms, stage of withdrawal, medical and psychiatric complications, co-
morbid polysubstance abuse, patient cooperation, ability to follow instruc-
tions, social support systems, and patient history, some patients can be safely
detoxified in outpatient settings with limited medical supervision (Blondell
2005).
Symptom-triggered BZD administration. Symptom-triggered BZD ad-
ministration is frequent in withdrawal protocols (Jaeger et al. 2001). The revised
250 Clinical Manual of Psychosomatic Medicine

Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale is the

most commonly used instrument to gauge the severity of alcohol withdrawal
(Sullivan et al. 1989; Williams et al. 2001). Ten domains (nausea, diaphoresis,
anxiety, agitation, headache, tremor, clouding of sensorium, and auditory, visual,
and tactile disturbances) are scored hourly, and the BZD dose administered is pro-
portional to the severity rating; when the rating falls to a mild level, the intervals
between assessments are lengthened and patients receive lower BZD doses.

Potential Complications
Medical Complications
Medical complications of chronic alcohol abuse include anemia, esophageal
disorders, gastritis, alcoholic hepatitis, cirrhosis, pancreatitis, cardiomyopathy,
insomnia, male feminization and impotence, myopathy, peripheral neuropa-
thy, falls and traumatic accidents (leading to fractures, brain injury, subdural
hematoma, etc.), Wernicke-Korsakoff syndrome, and dementia. Physical ex-
amination may identify bruises, spider angiomata, ascites, muscle wasting, nys-
tagmus, and ataxia.
Management. Advising a medically ill alcoholic patient to drink in moderation
is foolish. After the patient is stabilized, the clinician should encourage the patient
to become involved in community resources, especially Alcoholics Anonymous
(AA). Although various life circumstances motivate 20%–30% of patients to
achieve long-term remission without structured assistance (Rumpf et al. 2006), of
the patients who seriously commit to treatment, 50%–60% achieve substantial
functional improvement in the following year (Moos and Moos 2006). Both in-
patient and outpatient programs should be considered.
Pharmacological aids to relapse prevention. For a patient without signifi-
cant hepatic compromise who has realistic access to regular follow-up, and es-
pecially if his or her history includes abstinence that gave way to impulsive
drinking, the consultation psychiatrist should urge prompt follow-up with a
primary care physician to consider an antidipsogenic medication. Current op-
tions include the following:

• Disulfiram—precipitates accumulation of acetaldehyde, a metabolite of

ethanol, by enzyme inhibition, resulting in distinctly noxious flushing,
 Substance-Related Disorders 251

nausea, diaphoresis, and tachycardia if any alcohol is consumed—even

small amounts from over-the-counter liquid medications
• Naltrexone—an opioid antagonist that inhibits the expected rise in endor-
phins after alcohol consumption, thereby reducing craving by decreasing the
reinforcing pleasure obtained by a drink following a period of abstinence
• Acamprosate—a glutamatergic blocker and γ-aminobutyric acid (GABA)
agonist with an uncertain mechanism of action, although it may success-
fully attenuate destabilizing effects of alcoholism on the balance between
excitatory and inhibitory neurotransmission in the brain

These agents are typically not initiated on the consultation service because
they best serve patients when integrated with ongoing assistance, whether in
formal treatment programs, self-help programs, or consistent primary care
follow-up.
Special considerations in medically ill patients. Although disulfiram is the
oldest of the three pharmacological aids to relapse prevention, it has the least
support for outcome effectiveness, whereas acamprosate has garnered fair evi-
dence of benefit, and naltrexone has a strong evidence base for its effective-
ness. Disulfiram can have serious side effects that include hepatotoxicity and
depression, further limiting its use in medically ill patients. Although the de-
cision is controversial, the U.S. Food and Drug Administration has deter-
mined that due to potential hepatotoxicity, naltrexone is contraindicated for
patients with severe hepatic disease; this is not an absolute contraindication,
but naltrexone requires careful monitoring when used in the context of exist-
ing hepatic compromise. In contrast, acamprosate has no known risk of hepa-
totoxicity or significant drug interactions, making it a good choice in patients
who are medically ill. However, the dosage should be reduced in patients with
impaired renal function, and acamprosate should be avoided completely in
the presence of renal failure.

Alcohol Overdose
The lethal level of alcohol does not increase as tolerance develops (Mebane
1987). The LD50 (defined as a lethal dose in 50% of patients) of alcohol is
500 mg/dL. Signs of life-threatening alcohol overdose are unresponsiveness,
slow and shallow breathing, and cardiac dysrhythmia.
252 Clinical Manual of Psychosomatic Medicine

Management. Intubation if respiratory failure appears imminent, aggres-

sive hydration, and other cardiovascular support measures may all be required.
Hemodialysis is an option in potentially life-threatening alcohol overdoses.

Alcohol-Induced Psychotic Disorder

A diagnosis of alcohol-induced psychotic disorder requires the presence of
psychosis following a history of recent heavy alcohol use (unless the distur-
bance is accounted for by schizophrenia or a psychotic mood disorder). Au-
ditory hallucinations are more prominent than other withdrawal symptoms,
last at least 1 week, and occur while the patient has a clear sensorium.

Management. When patients develop alcohol-induced psychotic disorder

during detoxification, an antipsychotic is typically necessary to control agita-
tion and hallucinations. A conventional agent such as haloperidol offers the
advantages of lower cost and more experience in medically ill patients. After
symptoms cease, antipsychotics should be discontinued.

Alcohol Withdrawal Seizures

Alcohol withdrawal seizures occur in fewer than 5% of unmedicated patients;
individuals with a history of prior brain injury, previous withdrawal seizures,
or an existing seizure disorder all incur higher risk. Seizures typically occur 8–
36 hours after the last alcohol use, with peak frequency during the second day
after cessation of alcohol use. One-third of patients who have withdrawal sei-
zures go on to develop alcohol withdrawal delirium, or delirium tremens
(DTs).

Management. BZDs are the treatment of choice for alcohol withdrawal sei-
zures, but intramuscular administration should be avoided because of variable
absorption (lorazepam is an exception). Diazepam, 5–10 mg iv, is an effective
choice for immediate seizure control. Some clinicians prefer phenobarbital
because its very long half-life provides some protection against withdrawal
symptoms even if the patient leaves the hospital before withdrawal has been
completed. For underlying seizure disorders, a maintenance anticonvulsant
agent is necessary. The most effective way to prevent alcohol withdrawal sei-
zures is to detoxify the patient adequately with appropriate dosages of BZDs.
Patients who have histories of alcohol withdrawal seizures warrant particularly
 Substance-Related Disorders 253

close monitoring of serum magnesium, with parenteral replacement if they

develop marked hypomagnesemia.

Alcohol Withdrawal Delirium

DTs begin 2–7 days after cessation of drinking. The risk for DTs is highest
when the patient has a long history (>10 years) of heavy drinking and a major
medical illness, especially liver disease, infection, trauma, poor nutrition, or
metabolic disorders. Clinical signs and symptoms of DTs are disorientation,
agitation, visual or tactile hallucinations, autonomic hyperactivity, tremor,
ataxia, fever, and dilated pupils. Alcohol withdrawal delirium is potentially life
threatening. If unrecognized and untreated, mortality can approach 40%;
however, the mortality rate for hospitalized patients is less than 5% (Yost
1996). When patients die during DTs, the cause of death is usually heart fail-
ure, infection, or traumatic injury.
Management. The management of alcohol withdrawal delirium is similar
to that for uncomplicated alcohol withdrawal, except much higher dosages of
BZDs are often required, and concomitant antipsychotics are often necessary
to adequately control confusion, delusions, hallucinations, or agitation. Ad-
ministration of thiamine, with careful attention to fluid and electrolyte im-
balance, is imperative.

Wernicke-Korsakoff Syndrome
Wernicke-Korsakoff syndrome is rare, occurring in less than 1% of alcohol-
dependent individuals, but the consequences can be devastating (Thompson
and Marshall 2006). Wernicke’s encephalopathy begins with an abrupt onset
of truncal ataxia, ophthalmoplegia (usually third nerve palsy), and delirium.
Ataxia may precede the delirium, which is marked by lethargy, somnolence,
and profound apathy. The clinician should not wait for all three signs; the
presence of two suggests Wernicke’s encephalopathy. The etiology of the dis-
order is thiamine deficiency; prompt replacement can begin to reverse ocular
symptoms within a few hours and thereby offer confirmation of the diagnosis.
Long- and short-term memory impairment (Korsakoff syndrome) usually de-
velops if Wernicke’s encephalopathy is unrecognized and goes untreated. In
Korsakoff syndrome, memory loss can be profound, but other cognitive func-
tions are relatively spared.
254 Clinical Manual of Psychosomatic Medicine

Management. The patient should be given thiamine, 100 mg/hour iv/im or

500 mg iv three times daily, until ophthalmoplegia begins to resolve, at which
point the patient is given thiamine, 100 mg/day parenterally, for at least 7 more
days to treat alcohol-induced persisting amnestic disorder. Ocular findings im-
prove first, followed by motor improvement; finally, mental status abnormali-
ties improve if the patient has not developed alcoholic dementia. Although the
delirium will almost invariably resolve (one-third in the first week, another
one-third in the first month, and the last one-third by 2 months), the amnestic
symptoms of Korsakoff syndrome resolve completely in only 25% of patients,
with another 25% showing no recovery and the remainder improving some-
what. Thiamine deficiency in alcohol-dependent patients may occur as a direct
consequence of alcohol consumption or as a part of the refeeding syndrome
that can follow the meager nutritional status of many patients who abuse alco-
hol (Mehanna et al. 2008).

Suicide
Suicide is the means of death for 1 of every 14 alcoholics (Inskip et al. 1998),
and multiple retrospective studies provide an average estimate of prior alcohol
abuse or dependence at nearly 50% of those who die by suicide (Conner and
Duberstein 2004); one-third of suicide completers had detectable alcohol in
their bodies at the time of death (Welte et al. 1988).
Predisposing factors. Predisposing factors (i.e., persisting vulnerabilities)
that reinforce the association of alcoholism and suicide include aggression,
impulsivity, hopelessness, negative affect, and severity of alcohol dependence
(Conner and Duberstein 2004).
Precipitating factors. Precipitating factors (i.e., time-limited events or situ-
ations) that occur within weeks or months of a suicide and appear to herald
junctures of high suicide risk among alcoholics include interpersonal trau-
matic experiences (especially the threatened or actual loss of a partner or rela-
tionship) and depressive episodes (Conner and Duberstein 2004).

Screening Tools
Several brief diagnostic screens are available to assist with diagnosis of alcohol
abuse and dependence (Soderstrom et al. 1997). Useful questionnaires and
laboratory tests are described.
 Substance-Related Disorders 255

Questionnaires
However well designed, no survey can yield the contextual perspective pro-
vided by an astute interview that focuses on chronic anxiety or dysphoria, past
injuries, job loss, financial problems, legal problems, and absenteeism. Nev-
ertheless, several screening instruments are commonly used.

Alcohol Use Disorders Identification Test. The Alcohol Use Disorders Iden-
tification Test (AUDIT) consists of 10 multiple-choice questions regarding the
quantity and frequency of a patient’s alcohol consumption, drinking behavior,
and alcohol-related problems (Reinert and Allen 2007). Although the AUDIT
is commonly regarded as the gold standard for screening, not all patients who
are acutely ill or otherwise poorly disposed to speaking with a psychiatrist will
cooperate with the full AUDIT. The following three-item version, the AUDIT-
C, has nearly identical sensitivity to the full AUDIT (Bradley et al. 2007):

1. How often do you have a drink containing alcohol? [Score ranges from 0
(never) to 4 (four or more times per week)]
2. How many drinks containing alcohol do you have on a typical day when
you are drinking? [Score ranges from 0 (one or two drinks) to 4 (10 or
more drinks)]
3. How often do you have six or more drinks on one occasion? [Score ranges
from 0 (never) to 4 (daily or almost daily)]

CAGE screen for diagnosis of alcoholism. The CAGE screen includes

four items, easily recalled using the acronym CAGE. Scores of 2 have a sensi-
tivity of 50% for heavy drinkers and 75% for those with alcohol dependence,
and a specificity of about 80% (Schuckit 2009). The examiner begins each of
the following questions with “Have you ever...”

C Thought you should CUT BACK on your drinking?

A Felt ANNOYED by people criticizing your drinking?
G Felt GUILTY or bad about your drinking?
E Had a morning EYE-OPENER to relieve hangover or nerves?

Brief Michigan Alcohol Screening Test. The Michigan Alcohol Screening

Test (MAST) consists of 25 questions answered simply yes or no. The Brief
256 Clinical Manual of Psychosomatic Medicine

Michigan Alcohol Screening Test (bMAST) is a shorter, valid 10-item version

(Connor et al. 2007).
TWEAK. A score of 3 or higher on the TWEAK screening questionnaire
indicates an alcohol problem (Russell et al. 1996). The acronym TWEAK
represents the following questions:

1. Tolerance (2 points): How many drinks can you hold? [≥6 indicates tol-
erance]
2. Worried (2 points): Does your spouse (or [do your] parents) ever worry or
complain about your drinking?
3. Eye openers (1 point): Have you ever had a drink first thing in the morn-
ing to steady your nerves or get rid of a hangover?
4. Amnesia (1 point): Have you ever awakened in the morning after some
drinking the night before and found that you could not remember a part
of the evening before?
5. [K] Cut down (1 point): Have you ever felt you ought to cut down on
your drinking?

Single-question screening. The National Institute on Alcohol Abuse and

Alcoholism recommends the following single question to screen for unhealthy
alcohol use:

• How many times in the past year have you had X or more drinks in a day?
(X=5 for males and 4 for females)

Any response of 1 or more is regarded as indicative of unhealthy alcohol use

(Smith et al. 2009). The single question is about 80% sensitive and specific for
detection of unhealthy alcohol use.

Laboratory Tests
Although results from several laboratory tests are highly suggestive of alcohol
abuse, no test is diagnostic. The following findings are potentially useful:

• Serum γ-glutamyltransferase is increased in more than half of problem

drinkers and in 80% of alcoholic patients with liver dysfunction (Schwan
et al. 2004; Trell et al. 1984).
 Substance-Related Disorders 257

• Carbohydrate-deficient transferrin is likely to increase with sustained

heavy drinking (Schuckit et al. 2009).
• Aspartate transaminase (AST) and alanine transaminase (ALT) levels are
also increased in heavy drinkers; an AST:ALT ratio of >2 suggests alco-
holic hepatitis (Schuckit et al. 2009).
• A very high blood alcohol level (>200 mg/dL) found in a nonintoxicated
patient, especially in an emergency department setting, is almost pathogno-
monic of alcohol dependence (Parker et al. 2008).
• Other laboratory indicators of alcohol abuse include increased uric acid,
increased red blood cell mean corpuscular volume, decreased white blood
cell and platelet counts, and increased triglycerides.

Sedatives, Hypnotics, and Anxiolytics

All BZDs and sedative-hypnotics induce tolerance to some degree. BZD and
barbiturate abuse and dependence may develop secondary to medical use or
street abuse. Barbiturates are less frequently abused because their role in anx-
iolysis has been supplanted by the BZDs, and neurologists now have many
other antiepileptic alternatives. Nonetheless, the clinician may encounter
butalbital (e.g., in the combination drug Fiorinal) and carisoprodol (e.g.,
Soma), either of which can precipitate serious difficulties, especially in over-
dose. Unfortunately, as with alcohol, although the barbiturate dose necessary
for intoxication increases with chronic abuse, the lethal dose does not.
Whereas the opiate-dependent patient may double the dose and still not ex-
perience respiratory depression, barbiturate-addicted patients can develop po-
tentially fatal respiratory depression with a dose only 20%–25% higher than
the usual daily dose. BZDs, in contrast, have a much higher LD50 than bar-
biturates. A simple diagnostic aid for abuse or dependence is a positive “shop-
ping bag sign.” The psychiatrist asks the patient’s family to bring in all the
patient’s medications. More than one BZD prescription obtained from differ-
ent physicians and filled at unassociated pharmacies betrays a problem. For
managing sedative-hypnotic dependence in medical patients, simplification
of medication regimens, agreement that one physician will manage sedative-
hypnotic prescriptions, and gradual tapering may suffice. However, not all
chronic BZD users are abusing these medications, and these individuals
should not be regarded as certain future abusers. Legitimate reasons exist for
258 Clinical Manual of Psychosomatic Medicine

chronic use of BZDs, and any taper must be accompanied by conscientious

assessment for an underlying justifiable clinical indication.
Intoxication
Recognition
Symptoms and signs of intoxication include the following:

• Disinhibition
• Mood lability
• Dysarthria
• Ataxia
• Hyporeflexia
• Nystagmus
• Impaired attention

The symptoms and signs are similar to those of alcohol intoxication. Acciden-
tal, iatrogenic, or suicidal overdose may cause respiratory depression. Cross-
reactivity occurs between alcohol, BZDs, and sedative-hypnotics.
Management

1. Patient should be monitored closely for respiratory depression.

2. Patient should be moved to intensive care unit if he or she becomes stu-
porous, hypoxic, or unresponsive.
3. Agitation may be managed with haloperidol administered intravenously
or intramuscularly.
4. Flumazenil, a BZD antagonist, can reverse coma in a BZD overdose but
requires careful titration in a BZD-dependent patient to avoid inducing
seizures.

Withdrawal
Recognition
Symptoms and signs of withdrawal include the following:

• Nausea
• Tremor
• Hyperreflexia
• Hyperphagia
 Substance-Related Disorders 259

• Tachycardia
• Dilated pupils
• Diaphoresis
• Irritability
• Insomnia
• Restlessness
• Anxiety

Fever, autonomic hyperactivity, seizures, and delirium can occur in severe

cases. The features of sedative, hypnotic, or anxiolytic withdrawal are similar
to those of alcohol withdrawal and can be life threatening. The time of onset
and the duration of sedative-hypnotic withdrawal vary with the half-life of the
drugs; withdrawal is sometimes missed in hospitalized patients because of a
low index of suspicion or because symptoms can occur 7–10 days after admis-
sion with a drug that has a long half-life.

Management

1. Baseline dosage should be established. (The dosage may be higher than

patient has acknowledged.)
2. If agent has a short half-life (e.g., alprazolam), patient should be switched
to a long-half-life alternative (e.g., clonazepam or diazepam).
3. Average daily dosage should be administered for 2 days; then taper should
begin.
4. The rate of taper varies with collateral factors but should not exceed 10%
per day (Franklin et al. 2002).

Potential Complications
Long- and short-term memory impairment may occur after prolonged, heavy
use of a sedative-hypnotic agent. This disorder, termed sedative-, hypnotic-, or
anxiolytic-induced persisting amnestic disorder, usually reverses gradually if
abstinence is achieved.

Opiates
Narcotics are used to relieve pain, cough, diarrhea, agitation, and severe anx-
iety for patients in the intensive care unit. Unfortunately, tolerance begins
260 Clinical Manual of Psychosomatic Medicine

within days, compromising potential effectiveness in long-term treatment.

Nonetheless, 20% of patients with chronic pain also use opiates regularly
(Chabal et al. 1997). Psychiatrists are often consulted to examine patients in
pain who do not appear to respond to an “adequate” narcotic regimen, or to
evaluate a patient’s perceived overuse of narcotics. In the course of such con-
sultations, underuse rather than abuse of narcotic analgesics is often found.
Additionally, more than 90% of opiate-addicted patients have at least one
other psychiatric disorder, most commonly depression, alcoholism, or antiso-
cial personality disorder (Khantzian and Treece 1985).

Intoxication
Recognition
Symptoms and signs of opiate intoxication include the following:

• Apathy
• Dysphoria or euphoria
• Psychomotor retardation
• Drowsiness
• Dysarthria
• Pinpoint pupils (except with meperidine)

In severe cases, respiratory depression, stupor, or coma can occur; nystagmus

is rare. Clinicians should suspect an opiate overdose in any patient who pre-
sents in a coma, especially when accompanied by respiratory depression and
pupillary constriction.

Management

1. Patient should be monitored for respiratory depression, pulmonary

edema, and seizures.
2. Patient should be given naloxone 0.4 mg iv every 3–5 minutes until
symptoms clear. Naloxone has a short duration of action relative to al-
most every opiate.
3. After stabilization and acute detoxification, patient should be referred for
treatment.
 Substance-Related Disorders 261

4. Methadone programs achieve higher success and retention rates than pro-
grams that require abstinence.

Withdrawal
Recognition
Narcotic or opioid withdrawal is uncomfortable but rarely life threatening.
Classic features include pupillary dilation, yawning, piloerection, rhinorrhea,
nausea, fever, hypertension, tachycardia, cramps, drug craving, insomnia, rest-
lessness, irritability, and seizures. The presentation and course of symptoms in
opioid withdrawal vary with the half-life of the agent and the patient’s hepatic
status; untreated symptoms can last 2–4 weeks in patients dependent on meth-
adone.

Management

1. Baseline dosage needs to be established. Because dosage may be higher or

lower than patient has acknowledged, withdrawal needs to be gauged
through assessment of objective markers such as heart rate, respiratory
rate, and pupillary size.
2. If agent of abuse has a short half-life, patient needs to be switched to a
long-half-life alternative.
3. Average daily equivalent dosage should be administered for 2 days; then
taper should begin.
4. Rate of taper varies with collateral factors but should not exceed 10% per
day.
5. Established methadone-maintenance patients should be maintained on
usual daily oral dosage, as confirmed by outpatient program staff.
6. Buprenorphine may be dispensed only by qualified physicians who have
completed advanced mandatory training and is available only in selected
settings.

Amphetamines
Amphetamines block the reuptake of dopamine, serotonin, and norepinephrine
and profoundly affect dopamine storage release. Amphetamines are especially
262 Clinical Manual of Psychosomatic Medicine

abused by night workers, students, dieters, persons who work long hours, and
persons who are chronically dysphoric. Legitimate medical uses of amphet-
amines include treatment of depression, attention-deficit/hyperactivity disorder,
fatigue in multiple sclerosis, and narcolepsy; typical dosages range from 5 to ≥50
mg/day. On the street, daily doses often reach 100 mg or more. Higher doses can
cause psychosis or delirium. Repeated use leads to postintoxication depression,
which can perpetuate further abuse. The clinician should obtain a toxicology
screen because polydrug abuse is common. Poor nutrition may lead to anemia.

Intoxication
Recognition
The following are symptoms and signs of mild amphetamine intoxication:

• Euphoria
• Heightened self-esteem
• Grandiosity
• Anxiety
• Suspiciousness
• Miosis
• Tachycardia
• Nausea
• Perspiration
• Hypertension
• Restlessness

More severe intoxication leads to paranoia, hypervigilance, hallucinations,

agitation, delirium, arrhythmias, and convulsions.

Management

1. Staff should try to defuse the tension by talking to the patient.

2. Urine should be acidified with vitamin C to speed elimination.
3. Patient should be observed for dysrhythmias, hypertension, fever, and sei-
zures.
4. Staff should remain alert for violent or suicidal ideation and behavior.
 Substance-Related Disorders 263

5. Patient should be given lorazepam 2–4 mg iv/im every 2 hours for severe
anxiety or agitation.
6. A toxicology screen should be done to assess for other drug use.
7. Disruptive paranoia or delusions warrant antipsychotic use.

Withdrawal
Recognition
When amphetamines are abruptly discontinued, various treatable postintox-
ication findings can occur:

• Depression (especially if the patient has prior existing risk for depression)
• Irritability
• Anxiety
• Fatigue
• Insomnia or hypersomnia
• Drug craving
• Psychomotor agitation
• Hyperphagia

Management

1. Acute management strategies for amphetamine withdrawal are the same

as for intoxication.
2. Patient should be watched for potential emergence of acute rebound de-
pression.
3. Patient should be watched for suicidal and drug-seeking behavior.
4. The consultant should not reinitiate amphetamine to ameliorate with-
drawal symptoms.

Potential Complications
Amphetamine Intoxication Delirium
Amphetamine intoxication delirium, or an agitated confusional state, may de-
velop within 24 hours of amphetamine use. Hallucinations, delusions, and
signs of autonomic hyperactivity are frequently present.
264 Clinical Manual of Psychosomatic Medicine

Management. Management of amphetamine intoxication delirium mirrors

the approach to amphetamine intoxication, with one important exception:
instead of verbal efforts to calm the patient, an antipsychotic should be ad-
ministered.

Amphetamine-Induced Psychotic Disorder

Amphetamine-induced psychotic disorder can last several days in a patient
with a clear sensorium. Amphetamine psychosis resembles acute paranoid
schizophrenia.
Management. Management of amphetamine-induced psychotic disorder is
the same as for amphetamine intoxication delirium.

Street Names for Amphetamines

Street names for amphetamines include black beauties, crank, crystals, cat, ice,
meth, pep pills, smart drug, speed, and uppers. Street names for 3,4-methylene-
dioxymethamphetamine (MDMA, commonly called ecstasy) include Adam, E,
lollies, love drug, smarties, vitamin E, and XTC (Erickson et al. 2007).

Cocaine
Cocaine blocks the reuptake of neuronal dopamine, serotonin, and norepi-
nephrine. Cocaine has a fairly specific activating effect on mesocortical and
mesolimbic dopaminergic pathways. Dopamine is an important neurotrans-
mitter in limbic pleasure centers, including those related to food and sexual
activity. A patient’s inability to control cocaine intake is probably related to
the highly rewarding properties of the drug. With repeated cocaine use, tol-
erance develops secondary to decreased reuptake inhibition and altered recep-
tor sensitivity. Cocaine also causes cortical kindling (Halikas et al. 1991), the
process by which brief bursts of central nervous system stimulation at regular
intervals result in lasting changes in brain excitability. Limbic areas of the
brain are uniquely sensitive to kindling. The chronic cocaine user may have
severe financial problems because of the large amounts of the drug needed to
“chase another high” or stave off the cocaine “crash.” When a patient who
abuses cocaine is admitted to the hospital, the staff should watch for drug-
seeking behavior, depression, suicidal behavior, and insomnia. A toxicology
 Substance-Related Disorders 265

screen can help make the diagnosis (but may be negative if the patient last
used cocaine 36 hours before) and rule out potential contributions by other
drugs of abuse. After the patient is medically stabilized, he or she should be re-
ferred for treatment. Inpatient drug rehabilitation is indicated if outpatient
treatment has failed, the patient is unmotivated, concurrent psychiatric illness
is present, or a complicating psychosocial situation exists.

Intoxication
Recognition
Features of cocaine intoxication vary but may include the following:

• Euphoria
• Grandiosity
• Hypervigilance
• Increased libido
• Psychomotor agitation
• Tachycardia
• Miosis
• Hypertension
• Perspiration
• Nausea
• Delirium
• Hallucinations

Sudden death has been reported with acute cocaine intoxication; death usu-
ally is the result of cardiac arrest or ventricular fibrillation. Cocaine binges can
last a few hours to several days. Tolerance to the euphoric effects develops rap-
idly during the course of a binge.

Management

1. Presence of family or friends may suffice for the acute phase.

2. Lorazepam 2–4 mg iv/im should be administered every 2 hours for severe
anxiety or agitation.
3. Patient should be observed for dysrhythmias, psychosis, and precipitous
suicidality.
266 Clinical Manual of Psychosomatic Medicine

4. Cardiac monitoring and prompt access to airway support are necessary

only for 4–6 hours because cocaine is rapidly metabolized and acute, life-
threatening levels decline rapidly; use of beta-blockers is controversial due
to the risk of consequent unopposed alpha activity by cocaine.
5. Prolonged cocaine use is often followed by severe dysphoria.
6. If dysphoria persists, safety may require inpatient psychiatric care.

Withdrawal
Recognition
Although abrupt discontinuation of cocaine is medically safe, postintoxica-
tion sequelae can occur after prolonged use. For most patients, the worst dys-
phoria and craving occur in the first day of abstinence. However, profound
dysphoria may last 2 weeks or longer, typically accompanied by strong drug
craving and insomnia. After several weeks of improvement, the patient may
experience a second period of craving and depression, which resolves slowly
over weeks to months (Gawin and Kleber 1986). Episodic craving, often trig-
gered in response to environmental stimuli, can continue indefinitely.

Management
When a patient accustomed to chronic cocaine abuse is obliged to withdraw
because he or she is hospitalized for other medical or surgical reasons, the psy-
chiatric consultant should advise the primary team of the phases of abstinence
and watch for suicidal and drug-seeking behavior. If persistent dysphoria and
associated symptoms meet criteria for major depression, antidepressant ther-
apy is indicated.

Potential Complications
Cocaine Intoxication Delirium
Cocaine intoxication delirium, an agitated confusional state, may appear
within 24 hours of cocaine use.
Management. Management of cocaine intoxication delirium requires ob-
taining a toxicology screen, monitoring for seizures and dysrhythmias, and
proactively treating escalating anxiety and agitation with parenteral loraz-
 Substance-Related Disorders 267

epam. Because violence is common, prompt access to antipsychotics, ample

security support, and physical restraints may be necessary.

Cocaine-Induced Psychotic Disorder

Paranoid delusions can appear shortly after cocaine use. Unlike the confu-
sional state, psychosis is often prolonged, lasting weeks or months in an occa-
sional patient.
Management. Psychiatric hospitalization is often required at the outset, and
ongoing scheduled antipsychotic medication is commonly necessary until the
psychotic symptoms dissipate entirely.

Street Names for Cocaine

Street names for cocaine include all-American drug, coke, crack, girl, mother
of pearl, nose candy, Peruvian powder, snow, toot, and white lady (Erickson et
al. 2007).

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PA R T I I I

Treatments
This page intentionally left blank
 14
Biological Treatments

A medically ill patient almost always receives medications. The patient’s

well-being is already threatened by the medical illness, and the patient’s health
should not be further compromised by medication-related adverse events.
Therefore, appropriate use of biological treatments in patients who are med-
ically ill requires careful consideration of the underlying medical illness, po-
tential alterations to pharmacokinetics, and drug-drug interactions.

Adherence to Pharmacological Treatment

Therapeutic Alliance
Developing a therapeutic alliance with the patient during the consultation and
follow-up is fundamental to achieving the best possible outcome. The patient
has beliefs about psychiatric medications that must be explored and clarified.
Many patients are affected by feelings of failure about needing a medication,
fear of addiction, magical hopes for cure, and transference toward the physi-
cian. A discussion that includes the patient as a partner facilitates formation of
the doctor-patient alliance.

273
274 Clinical Manual of Psychosomatic Medicine

Education About the Medication

Patients benefit from education about medication. An integral part of this
process includes a realistic discussion of potential adverse effects, proper ad-
ministration of the medication, expected time to response, and guidelines for
missed doses. Discussions such as these have been found to improve patients’
attitudes toward medication, increase confidence that the side effects can be
managed, and improve adherence (Lin et al. 2003). Table 14–1 includes med-
ication principles to improve patient care and adherence.

Pharmacokinetics in Medically Ill Patients

Absorption
Orally administered drugs absorbed through the gastrointestinal tract may be
altered by first-pass hepatic metabolism before entering the systemic circula-
tion. Sublingual or topical administration of drugs decreases the first-pass ef-
fect, and rectal administration may reduce first-pass effect by 50%. Parenteral
administration generally results in rapid effects, but it is difficult to carry out
in adults, especially elderly patients, and the erratic absorption of some med-
ications given intramuscularly makes their clinical benefits less predictable.
Absorption may be affected by gastrointestinal diseases that result in changes
in gastric pH, rate of gastric emptying, or dysfunction or resection of the small
intestine. Liquid formulations may be better or more quickly absorbed than
solid drug preparations in patients with gastrointestinal disease. In patients
with renal disease, the alkalinizing effects of excess urea may increase absorp-
tion of psychotropic medications, but due to other physiological changes in
uremia, the effect is unpredictable. Absorption of drugs through the gas-
trointestinal tract may be decreased in patients with congestive heart failure
(Robinson and Owen 2005).

Drug Distribution
With the exception of lithium, psychotropic medications are lipophilic and
drawn to fatty tissues. Thus, psychotropic medications generally have large
volumes of distribution. As a person ages, the water content of the body de-
creases and the fat content rises, so the distribution volume of hydrophilic
 Biological Treatments 275

Table 14–1. Medication principles in the psychosomatic medicine

setting
Review all medications the patient is taking, including herbal and over-the-counter
medications.
Keep the medication regimen simple. Whenever possible, use only one medication to
treat a symptom or disorder.
Educate the patient about the medication. A therapeutic alliance is your best
guarantee of adherence.
Monitor target symptoms and side effects closely when starting a medication.
Remember that discontinuing a medication is often a valuable intervention,
especially when an elderly patient is taking multiple medications.
Avoid prescribing medications on an as-needed basis, particularly in patients with
pain, withdrawal syndromes, and delirium.
When as-needed medication dosing is required, monitor frequency of use to
determine a standing dosage.
Change one medication at a time, and use the minimum dose necessary to obtain the
desired response.
Treat prophylactically if a clear rationale exists (e.g., can give benztropine to avoid a
dystonic reaction from antipsychotics in an anxious young man with first-break
psychosis).
Use a medication that was previously effective for the patient or a family member
who had the same disorder.
If treatment fails, reexamine your diagnosis. Always reconsider the possibility of
occult substance abuse.
Note that serum drug levels are not a certification of efficacy or toxicity.
Be aware that generic drugs are cost-effective, but bioavailability can vary.
Recognize that social and characterological issues strongly influence treatment
acceptance and adherence.
Remember that each patient is unique.

Source. Reprinted from Fait ML, Wise MG, Jachna JS, et al.: “Psychopharmacology,” in The
American Psychiatric Publishing Textbook of Consultation-Liaison Psychiatry: Psychiatry in the Med-
ically Ill, 2nd Edition. Edited by Wise MG, Rundell JR. Washington, DC, American Psychiatric
Publishing, 2002, pp 939–987. Used with permission.
276 Clinical Manual of Psychosomatic Medicine

compounds is reduced in elderly patients, whereas that of lipophilic drugs is

increased. In addition, most psychiatric medications are bound to plasma pro-
teins, such as albumin and glycoproteins. When medication is bound to pro-
teins, it is not available for biological activity, such as occupying receptors in
the brain (Fait et al. 2002). Protein binding also complicates removal of toxic
levels of medications (e.g., by dialysis). The frequency of drug administration
is estimated by the length of its half-life. A steady-state drug level is generally
achieved after four to five half-lives of a drug.

Drug Metabolism
Hepatic Metabolism
When absorbed drugs first pass through the liver before entering the systemic
circulation, liver enzymes act on them; the metabolites produced may be psy-
chopharmacologically active or inert. Once in the liver, a medication, whether
on a first or a subsequent pass, is exposed to two main groups of metabolizing
enzymes.

• Phase I metabolism includes oxidation, reduction, and hydrolysis reactions,

although the oxidative process, which occurs via the monooxygenase or
cytochrome P450 (CYP) enzyme system, is most relevant to psychiatric
medications.
• Phase II metabolism consists of many conjugation pathways, the most com-
mon being glucuronidation; the medication or its metabolites are coupled
with polar groups to form more easily excreted (i.e., more hydrophilic)
compounds.

Most psychotropic drugs are metabolized primarily in the liver, so hepatic

insufficiency reduces their clearance. Hepatic clearance of the drug may be in-
fluenced by either the rate of delivery of the drug to the hepatic metabolizing
enzymes or by the intrinsic capacity of the enzymes to metabolize the substrate.

Cytochrome P450 System

Four CYP isoenzymes—CYP1A2, CYP2C (2C9/2C19), CYP2D6, and
CYP3A3/4—are especially important in the oxidative metabolism of medica-
 Biological Treatments 277

tions. Many genetic polymorphisms exist in the CYP isoenzymes and are seen
in a significant portion of the population. These genetic alterations may con-
tribute to either diminished metabolism, lack of metabolism, or excessive me-
tabolism of a compound. This genetic variability may explain some individual
sensitivity to specific drugs or failure to respond to others. Table 14–2 lists
some of the more common interactions among these enzymes and medica-
tions. Medications are often metabolized by a particular enzyme, can compete
for metabolism with other substrates, or can inhibit an enzyme without being
metabolized by it. Hepatic enzyme inhibition slows metabolism (i.e., increases
the half-life) and increases the concentration and potential toxicity of psycho-
tropic and other drugs affected.

Drug Elimination
Nearly all psychotropic drugs are metabolized by the liver and eliminated in
bile, which is then excreted in feces. Some medications are metabolized to ac-
tive compounds that are excreted in the urine. (Specific drugs and their use in
patients with renal and liver failure are described later in this chapter under
“Psychotropic Use in Renal Disease” and “Psychotropic Use in Liver Disease,”
respectively.) Drug excretion via the kidneys declines with age; therefore, el-
derly patients may need dose adjustments (Turnheim 2003). Creatinine clear-
ance is a more reliable indicator of renal function than serum creatinine.

Drug Interactions
Recognizing drug interactions is a crucial part of consultation work (see Table
14–2). The effect of one drug on another can be pharmacokinetic (i.e., affecting
the absorption, distribution, biotransformation, and excretion of the other
drug) or pharmacodynamic (i.e., changing the effect of the drug at its point of
action) (Fait et al. 2002). The clinician should obtain a complete medication
list, including medications recently discontinued, over-the-counter medica-
tions used, and herbal or other alternative drug preparations used. The clini-
cian should also ask a family member to bring in all medications from the
patient’s house.
278 Clinical Manual of Psychosomatic Medicine

Table 14–2. Cytochrome P450 (CYP)–drug interactions

Substrates Inhibitors Inducers

CYP1A2
Psychotropic Caffeine Fluoxetine Caffeine
Clozapine Fluvoxamine Carbamazepine
Duloxetine Tobacco
Haloperidol Modafinil
Olanzapine
Propranolol
Tertiary-amine TCAs
(amitriptyline,
imipramine)
Nonpsychotropic Cyclobenzaprine Cimetidine Charbroiled foods
Propranolol Ciprofloxacin Cruciferous
Tamoxifen Erythromycin vegetables
Theophylline Ketoconazole Lansoprazole
Verapamil Grapefruit juice Omeprazole
Warfarin Isoniazid Phenobarbital
Phenytoin
Rifampin
CYP2C (2C9/2C19)
Psychotropic Barbiturates Fluoxetine Carbamazepine
Cannabinoids Fluvoxamine St. John’s wort
Diazepam Modafinil Valproate
Propranolol Tranylcypromine
Tertiary-amine TCAs
 Biological Treatments 279

Table 14–2. Cytochrome P450 (CYP)–drug interactions

(continued)
Substrates Inhibitors Inducers

CYP2C (2C9/2C19) (continued)

Nonpsychotropic Lansoprazole Cimetidine Phenobarbital
NSAIDs Fluconazole Phenytoin
Omeprazole Miconazole Rifampin
Oral hypoglycemics Omeprazole
Losartan Phenylbutazone
Phenytoin Simvastatin
Propranolol Sulfonamides
Tamoxifen Ticlopidine
Tolbutamide
Valsartan
Warfarin
CYP2D6
Psychotropic Clozapine Atomoxetine Not induced
Duloxetine Bupropion
Haloperidola Duloxetine
Olanzapine Fluoxetine
Paroxetine Fluphenazine
Phenothiazinesb Fluvoxamine
Risperidone Haloperidol
TCAs Methylphenidatec
Trazodone Norfluoxetine
Venlafaxine Paroxetine
Phenothiazinesb
Sertraline
TCAs
280 Clinical Manual of Psychosomatic Medicine

Table 14–2. Cytochrome P450 (CYP)–drug interactions

(continued)
Substrates Inhibitors Inducers

CYP2D6 (continued)
Nonpsychotropic Beta-blockers Amiodarone
Cyclobenzaprine Cimetidine
Codeine Quinidined
Hydrocodone
Oxycodone
Type 1C
antiarrhythmics
(flecainide,
propafenone)
CYP3A3/4
Psychotropic Alprazolam Cannabinoids Carbamazepine
Aripiprazole Fluoxetine Modafinil
Bupropion Fluvoxamine St. John’s wort
Buspirone Norfluoxetine
Caffeine Sertraline
Cannabinoids
Clonazepam
Fluoxetine
Carbamazepine
Clozapine
Midazolam
Modafinil
Quetiapine
Sertraline
Tertiary-amine TCAs
Triazolam
Venlafaxine
Ziprasidone
 Biological Treatments 281

Table 14–2. Cytochrome P450 (CYP)–drug interactions

(continued)
Substrates Inhibitors Inducers

CYP3A3/4 (continued)
Nonpsychotropic Anticancer drugs Amiodarone Dexamethasone
Antiretroviral agents Cimetidine Isoniazid
Astemizole Ciprofloxacin Phenobarbital
Calcium channel Cyclosporine Phenytoin
blockers Diltiazem Primidone
Cisapride Erythromycind Rifabutin
Cyclosporine Fluconazole Rifampin
Cyclobenzaprine Grapefruit juice
Erythromycin Itraconazoled
HMG-CoA reductase Ketoconazoled
inhibitors Miconazole
Itraconazole Protease inhibitors
Ketoconazole
Lidocaine
Omeprazole
Tamoxifen
Quinidine
Steroids
Warfarin
Note. Table includes both in vivo and in vitro data. Tricyclic antidepressants (TCAs) are metab-
olized by CYP2D6, CYP3A, CYP2C, and CYP1A2. HMG-CoA=3-hydroxy-3-methylglutaryl-
coenzyme A; NSAIDs=nonsteroidal anti-inflammatory drugs.
aComplex interaction.
b
Phenothiazines include chlorpromazine, prochlorperazine, perphenazine, trifluoperazine, flu-
phenazine, thioridazine, and mesoridazine.
cMethylphenidate likely has CYP effects, but particular isoenzymes have not been identified.
d
Extraordinarily powerful inhibitors of CYP enzymes, sometimes referred to as “killers.”
Source. Reprinted from Robinson MJ, Owen JA: “Psychopharmacology,” in The American Psy-
chiatric Publishing Textbook of Psychosomatic Medicine. Edited by Levenson JL. Washington, DC,
American Psychiatric Publishing, 2005, pp. 871–922.
282 Clinical Manual of Psychosomatic Medicine

Serotonin Syndrome
Non-Idiopathic Drug Reaction
In contrast to neuroleptic malignant syndrome (NMS), serotonin syndrome
is not an idiosyncratic drug reaction and is generally dose related. Therefore,
the risk factors for serotonin syndrome are pharmacologically related, al-
though constitutional factors may alter the threshold. Table 14–3 lists the
most common drugs associated with serotonin syndrome.

Table 14–3. Drugs associated with serotonin syndrome

Selective serotonin reuptake inhibitors: citalopram, escitalopram, fluoxetine,
fluvoxamine, paroxetine, sertraline
Tricyclic antidepressants: amitriptyline, desipramine, doxepin, imipramine,
maprotiline, nortriptyline, protriptyline, trimipramine
Monoamine oxidase inhibitors: phenelzine, tranylcypromine, isocarboxazid
Serotonin-norepinephrine reuptake inhibitors: venlafaxine, desvenlafaxine,
duloxetine, milnacipran
Other antidepressants: bupropion, mirtazapine, trazodone
Anxiolytic: buspirone
Mood stabilizer: lithium
Herbal products: St. John’s wort (Hypericum perforatum), tryptophan, ginseng
Amphetamines and amphetamine derivatives
L-Dopa

Drugs of abuse: cocaine, methylenedioxymethamphetamine (MDMA), lysergic acid

diethylamide (LSD), Syrian rue
Analgesics: fentanyl, tramadol, meperidine
Antimigraine drugs: triptans
Antiemetic agents: ondansetron, metoclopramide, granisetron
Over-the-counter cold remedies: dextromethorphan
Antibiotics: linezolid (monoamine oxidase inhibitor)
Bariatric medications: sibutramine
 Biological Treatments 283

Spectrum of Findings
Clinical manifestations of serotonin syndrome range from barely perceptible
to fatal (Figure 14–1).

Clinical Triad
Manifestations of serotonin syndrome are described in a clinical triad: mental
status changes, autonomic hyperactivity, and neuromuscular abnormalities.
Findings, however, are not consistent across patients.
Mental Status Changes
Changes in mental status range from mild restlessness to elevated mood and
agitated delirium. Progression to coma may occur in severe cases.

Altered Clonus
Akathisia Hyperthermia
mental status (sustained)

Life-
Mild threatening
symptoms toxicity

Tremor Clonus Muscular

(inducible) hypertonicity

Figure 14–1. Serotonin syndrome: spectrum of clinical findings.

Manifestations of serotonin syndrome range from mild to life-threatening. The verti-
cal arrows suggest the approximate point at which clinical findings initially appear in
the spectrum of the disease, but all findings may not be consistently present in a single
patient with serotonin syndrome. Severe signs may mask other clinical findings. For
example, muscular hypertonicity can overwhelm tremor and hyperreflexia.
Source. Reprinted from Boyer EW, Shannon M: “The Serotonin Syndrome.” New
England Journal of Medicine 352:1113, 2005. Used with permission.
284 Clinical Manual of Psychosomatic Medicine

Autonomic Hyperactivity
Vital sign abnormalities include tachycardia in mild to moderate cases, and
hypertension or hypotension and hyperthermia in severe cases. Physical ex-
amination reveals diaphoresis, mydriasis, hyperactive bowel sounds, and shiv-
ering. Symptoms of diarrhea and nausea are also common.

Neuromuscular Abnormalities
Neuromuscular abnormalities include tremor, hyperreflexia, clonus (induc-
ible, spontaneous, and ocular), and muscular rigidity, which are often more
pronounced in the lower extremities than in the upper extremities.

Diagnosis
Although several diagnostic criteria have been developed, no formal consensus
exists regarding the criteria for serotonin syndrome. Laboratory findings do
not confirm the diagnosis, although in severe cases, laboratory findings may
include metabolic acidosis, rhabdomyolysis, elevated serum aminotransferase,
elevated creatinine, and disseminated intravascular coagulopathy (Boyer and
Shannon 2005).

Differential Diagnosis
The differential diagnosis for serotonin syndrome includes NMS, catatonia,
malignant hyperthermia, and anticholinergic delirium (the first three of which
are described in more detail in the “Neuroleptic Malignant Syndrome” section
below). Table 14–4 outlines the varying clinical presentations among serotonin
syndrome, anticholinergic delirium (“toxidrome”), NMS, and malignant hy-
perthermia.

Management
Serotonin syndrome is usually self-limited and resolves after discontinuation
of the offending agents. The consulting psychiatrist should do the following:

1. Provide necessary supportive care.

2. Discontinue serotonergic agents.
3. Consider administration of antiserotonergic agents. Cyproheptadine has
been recommended, but its efficacy has not been established.
 Biological Treatments 285

4. Control agitation with benzodiazepines and avoid physical restraints to

minimize muscle contractions that are associated with lactic acidosis and
hyperthermia.
5. Evaluate the need for psychopharmacological therapy before restarting
drug therapy. Limited data have been reported on drug rechallenge in pa-
tients who have developed serotonin syndrome (Boyer and Shannon
2005).

Neuroleptic Malignant Syndrome

Idiopathic Drug Reaction
In contrast to serotonin syndrome, NMS is an idiopathic drug reaction pos-
sibly caused by a decrease in central nervous system (CNS) dopamine activity,
but this theory has not been proven. Incidence rates as high as 3% have been
reported, but more recent data suggest an incidence of 0.01%–0.02% (Stub-
ner et al. 2004). The decreased frequency likely reflects better awareness of the
disorder and perhaps also a shift from use of typical to use of atypical antipsy-
chotics (Strawn et al. 2007). Although antipsychotics that are potent dopa-
mine blockers have generally been implicated, atypical antipsychotics are also
known to cause NMS. Nonpsychotropic medications such as metoclopra-
mide, droperidol, and promethazine may also cause NMS. An identical syn-
drome has been reported after abrupt discontinuation of dopamine agonists
in patients with Parkinson’s disease.

Risk Factors
Clinical, systemic, and metabolic factors have been associated with an in-
creased risk of NMS. Dehydration and conditions that promote dehydration,
such as poor oral intake, agitation, and fever, heighten risk (Levenson 1985).
Underlying brain abnormalities, concomitant use of lithium, and parenteral
administration or rapid dose escalation of antipsychotic medication also cor-
relate with NMS (Berardi et al. 1998; Pelonero et al. 1998; Smith et al. 2008).

Time Course
NMS most often develops over several days, and the majority of cases present
within 1 week from the initiation of an antipsychotic. NMS is less likely to de-
286 Clinical Manual of Psychosomatic Medicine

Table 14–4. Characteristics of serotonin syndrome and related

clinical conditions
Neuroleptic
Serotonin Anticholinergic malignant Malignant
syndrome “toxidrome” syndrome hyperthermia

Medication Proserotonergic Anticholinergic Dopamine Inhalational

history drug agent antagonist anesthesia
Time needed <12 hours <12 hours 1–3 days 30 minutes to
for condition 24 hours after
to develop administration
of inhalational
anesthesia or
succinylcholine

Vital signs Hypertension, Hypertension Hypertension, Hypertension,

tachycardia, (mild), tachycardia, tachycardia,
tachypnea, tachycardia, tachypnea, tachypnea,
hyperthermia tachypnea, hyperthermia hyperthermia
(>41.1°C) hyperthermia (>41.1°C) (can be as high
(typically as 46.0°C)
38.8°C
or less)
Pupils Mydriasis Mydriasis Normal Normal
Mucosa Sialorrhea Dry Sialorrhea Normal
Skin Diaphoresis Erythema, Pallor, Mottled
hot and diaphoresis appearance,
dry to touch diaphoresis
Bowel sounds Hyperactive Decreased or Normal or Decreased
absent decreased
Neuromuscular Increased, Normal “Lead-pipe” Rigor mortis–
tone predominantly rigidity like rigidity
in lower present in
extremities all muscle
groups
 Biological Treatments 287

Table 14–4. Characteristics of serotonin syndrome and related

clinical conditions (continued)
Neuroleptic
Serotonin Anticholinergic malignant Malignant
syndrome “toxidrome” syndrome hyperthermia

Reflexes Hyperreflexia, Normal Bradyreflexia Hyporeflexia

clonus (unless
masked by
increased
muscle tone)
Mental status Agitation, Agitated Stupor, alert Agitation
coma delirium mutism,
coma

Source. Reprinted from Boyer EW, Shannon M: “The Serotonin Syndrome.” New England
Journal of Medicine 352:1118, 2005. Used with permission.

velop 1 month or more after treatment initiation unless the dosage was in-
creased or an additional dopamine-blocking drug was added (Strawn et al.
2007). The mean recovery time is 7–10 days after discontinuation of the of-
fending agent (significantly longer if the antipsychotic was given as a depot in-
jection), although Caroff et al. (2000) reported that residual catatonia and
parkinsonism can persist for weeks after other symptoms have resolved.

Clinical Manifestations

• Hyperthermia is a cardinal feature of NMS, with a temperature typically

>38°C, and commonly >40°C.
• Muscular rigidity. Increased tone is an essential feature of NMS; superim-
posed tremor may result in a cogwheel phenomenon.
• Autonomic instability primarily includes tachycardia, hypertension or labile
blood pressure, and tachypnea. Autonomic volatility is a poor prognostic
sign.
• Altered mental status. Retrospective analyses indicate that mental status
changes or other neurological signs precede the systemic signs in 80% of
patients (Velamoor et al. 1994). Decreased levels of consciousness, includ-
ing stupor or progression to coma, commonly occur.
288 Clinical Manual of Psychosomatic Medicine

Laboratory Findings
No laboratory findings are specific for NMS, but elevated serum creatinine ki-
nase is associated with the syndrome. Other laboratory findings may include
increased white blood cell count, low serum iron, metabolic acidosis, and mild
elevations of lactate dehydrogenase and liver transaminases. Myoglobinuric
renal failure can develop from rhabdomyolysis (Strawn et al. 2007).

Differential Diagnosis
NMS is one disorder in a group of related conditions that share common features
of rigidity, hyperthermia, and autonomic dysregulation (see Table 14–4). Other
medical and neurological disorders, which have symptom overlap with NMS but
are unrelated to NMS, need to be considered in the differential diagnosis.

• Serotonin syndrome and NMS have similar presentations, although pa-

tients with serotonin syndrome are more likely to have myoclonus, hyper-
reflexia, shivering, nausea, and diarrhea.
• Malignant catatonia can appear indistinguishable from NMS (Mann et al.
1986), and some researchers have suggested that NMS is a drug-induced
form of malignant catatonia with the same underlying pathophysiology
(Fink 1996; Mann et al. 1986). The clinical history may include a psychi-
atric prodrome of psychosis, agitation, or catatonic excitement. The motor
findings in malignant catatonia are more likely to include dystonic postur-
ing, waxy flexibility, and stereotyped repetitive behaviors. Regardless of the
diagnosis, any dopamine receptor antagonists should be discontinued.
• A rare genetic disorder, malignant hyperthermia, is primarily differentiated
from NMS by the history of administration of a potent halogenated in-
halational anesthetic agent or succinylcholine.
• Anticholinergic toxicity is not associated with rigidity or diaphoresis, and
elevated body temperatures are less severe than in NMS. Mydriasis, flush-
ing, and bladder distention are more frequent than in NMS.
• Medical or neurological disorders with extrapyramidal symptoms from concom-
itant antipsychotic use are especially challenging to differentiate from NMS.
Diagnoses to consider include CNS infections, anatomic lesions that affect
the midbrain and brain stem structures, prodromal viral illnesses, seizures,
heatstroke, thyrotoxicosis, drug intoxication, and withdrawal from dopa-
mine agonists, baclofen, sedative-hypnotics, and alcohol (Strawn et al. 2007).
 Biological Treatments 289

Treatment
In many cases, discontinuation of the offending agent and supportive care are
sufficient for the resolution of NMS. Limited evidence suggests that specific
pharmacotherapy can facilitate recovery and decrease mortality. Especially be-
cause NMS has been conceptualized as a severe form of catatonia, the use of
benzodiazepines has been tried, with conflicting results (Caroff et al. 1998).
Given the relative risks and benefits, a trial of lorazepam administered parenter-
ally is a reasonable intervention, particularly for patients with less severe or pri-
marily catatonic symptoms (Strawn et al. 2007). Dopaminergic agents, includ-
ing bromocriptine and amantadine, and the muscle relaxant dantrolene have
been reported to hasten recovery and decrease mortality (Rosenberg and Green
1989; Sakkas et al. 1991). If supportive management and pharmacotherapy are
not adequate or malignant catatonia cannot be ruled out, electroconvulsive
therapy (ECT) is an effective treatment, even late in the course of NMS (Ad-
donizio and Susman 1987; Trollor and Sachdev 1999).

Antipsychotic Use Following NMS

Although estimates of up to 30% have been reported for the likelihood of de-
veloping NMS with antipsychotic use following an NMS episode, long-term
follow-up data have shown that the majority of patients can be safely restarted
on antipsychotic treatment (Levenson and Fisher 1988; Pope et al. 1991). At
least 2 weeks should elapse after recovery from NMS before rechallenge, and
low dosages of a low-potency typical antipsychotic or atypical antipsychotic
are preferred (Strawn et al. 2007).

Psychotropic Use and Cardiac Complications

Arrhythmias, QTc Prolongation, and
Risk of Sudden Cardiac Death
Antidepressants
Tricyclic antidepressants. Tricyclic antidepressants (TCAs) have quinidine-
like effects that may result in cardiac conduction delay, increased heart rate,
and prolongation of the QT, QRS, and PR intervals. Among patients without
cardiovascular disease, these effects are often insignificant, although they may
290 Clinical Manual of Psychosomatic Medicine

lead to ventricular arrhythmias in patients with preexisting conduction abnor-

malities or those taking type Ia antiarrhythmic drugs (Robinson and Levenson
2000). One study found that the risk of sudden cardiac death was not in-
creased with dosages less than 100 mg amitriptyline equivalents (Ray et al.
2004) (see also Chapter 10, “Mood Disorders”).
Selective serotonin reuptake inhibitors. In addition to the long-established
capacity of all of the TCAs to prolong the QTc interval, the U.S. Food and
Drug Administration (FDA) recently advised clinicians that the selective sero-
tonin reuptake inhibitor (SSRI) citalopram should no longer be used at dosages
greater than 40 mg/day. This recommendation was based on an as-yet-unpub-
lished prospective trial demonstrating that citalopram causes dose-dependent
QT interval prolongation (FDA Drug Safety Communication 2011).

Antipsychotics
The use of antipsychotics can result in QTc prolongation and risk of sudden
cardiac death (see also Chapter 7, “Delirium”).
Typical antipsychotics. All antipsychotics have the potential to produce
electrocardiographic changes, but not all drugs that prolong the QTc interval
result in torsade de pointes and sudden death. QTc prolongation is a warning
of the possibility of torsade de pointes and sudden death, but it is not the risk
itself. The evidence for torsade de pointes and sudden death is most robust
with thioridazine, pimozide, droperidol, and haloperidol. The risk is higher if
haloperidol is administered intravenously, given at high dosages, or used in
patients with cardiomyopathy (Di Salvo and O’Gara 1995; Hunt and Stern
1995; Reilly et al. 2000; Robinson and Levenson 2000).
Atypical antipsychotics. Although fewer data are available regarding atypi-
cal antipsychotics, emerging evidence suggests that atypical antipsychotics are
associated with elevated risk for sudden cardiac death (Jolly et al. 2009; Ray et
al. 2009). Among the atypical antipsychotics, ziprasidone appears to be the
most likely to cause QTc prolongation, and olanzapine and aripiprazole are
the least likely. A large retrospective cohort study showed that typical and
atypical antipsychotics have similar elevated risks of sudden cardiac death; the
risks were dose related for all agents (Ray et al. 2009). The incidence rate ratios
among users of high-dose antipsychotics compared with nonusers varied from
 Biological Treatments 291

1.72 for haloperidol to 5.05 for thioridazine (Ray et al. 2009). The ratios cor-
relate with an incidence rate of 3.3 events per 1,000 patient years among pa-
tients receiving higher dosages (Schneeweiss and Avorn 2009).

Factors Associated With QTc Prolongation

In addition to antiarrhythmics, antidepressants, and antipsychotics, certain
antihistamines and antimicrobial drugs are known to increase the QTc inter-
val. A careful review of medications is crucial to determine whether coadmin-
istration of drugs inhibits the metabolism of arrhythmogenic medications.
Factors that increase the likelihood of arrhythmia include congenital long QT
syndrome, age, preexisting cardiac disease, female gender, hypomagnesemia,
and hypokalemia (Elming et al. 2003).

Orthostatic Hypotension
TCAs, trazodone, and monoamine oxidase inhibitors commonly cause
orthostasis. Low-potency antipsychotics are more likely to cause orthostatic
hypotension than are high-potency antipsychotics, and among the atypical
antipsychotics, clozapine carries the greatest risk. Patients with congestive
heart failure or dehydration are particularly vulnerable to changes in blood
pressure (Smith et al. 2008).

Myocarditis and Cardiomyopathy

Myocarditis and cardiomyopathy are rare complications of clozapine, often
occurring early after treatment initiation, with one study showing a median
onset of 17 days (Haas et al. 2007; Mackin 2008).

Psychotropic Use and

Endocrine-Related Complications
Metabolic Syndrome
Metabolic syndrome is based on the co-occurrence of metabolic risk factors for
both type 2 diabetes mellitus and coronary vascular disease. These risk factors in-
clude abdominal obesity, hyperglycemia, dyslipidemia, and hypertension. Ques-
tions have been raised about the concept of metabolic syndrome and whether
the components of the syndrome warrant classification as an actual syndrome.
292 Clinical Manual of Psychosomatic Medicine

This uncertainty is partly due to the absence of a unifying pathogenesis for the
syndrome and lack of consensus regarding the definition (Kahn et al. 2005).
Olanzapine and clozapine, and to a lesser extent, quetiapine and risperidone, are
associated with weight gain, dyslipidemia, and new-onset diabetes mellitus (De
Hert et al. 2006; Henderson 2002; Henderson et al. 2000). Prior to initiation of
these atypical antipsychotics, minimum baseline screening should include fast-
ing blood glucose and lipid profile. Thereafter, the patient’s weight, blood pres-
sure, serum glucose, and lipids must be monitored, with testing frequency de-
termined by the patient’s medical history and risk factors. If a patient develops
impaired fasting glucose or dyslipidemia, consideration should be given to
switching to an atypical antipsychotic with lower risk of metabolic side effects
(e.g., ziprasidone or aripiprazole) or a typical antipsychotic (De Hert et al. 2006).

Thyroid Dysfunction
Among the psychotropics, lithium is the most commonly associated with thy-
roid dysfunction, including goiter, hypothyroidism, chronic autoimmune
thyroiditis, and possibly hyperthyroidism. Subclinical hypothyroidism has
been reported in up to 25% of patients, and prevalence estimates for overt
hypothyroidism range from 10% to 20%. Hypothyroidism can be treated and
should not be considered a contraindication to continued lithium therapy
(Robinson and Owen 2005).

Psychotropic Use in Renal Disease

Antidepressants
Studies are limited regarding treatment with antidepressants of patients with
end-stage renal disease (ESRD). The SSRIs have a more favorable side-effect
profile than the TCAs, especially because the hydroxylated metabolites of the
TCAs can be elevated in dialysis patients, potentially causing toxicity even at
therapeutic levels (Robinson and Levenson 2000). Dosage adjustments of flu-
oxetine, sertraline, or citalopram are generally not required for patients with
ESRD. Plasma levels of paroxetine are increased in patients with renal impair-
ment, and the recommended dosage is one-half of that for adults with normal
renal function. Clearances of venlafaxine and mirtazapine are reduced by
about 50% in patients with renal failure; therefore, a dosage reduction is rec-
ommended (L. M. Cohen et al. 2004; S. D. Cohen et al. 2007).
 Biological Treatments 293

Mood Stabilizers
Lithium is dialyzable and is therefore given to patients undergoing renal dial-
ysis after their dialysis treatments; the usual dose is 300–600 mg/day. Dialysis
patients do not eliminate lithium naturally, so they do not require daily lith-
ium supplementation aside from their postdialysis dose. Serum levels of lith-
ium are tested several hours after dialysis because plasma levels may actually
rise in the postdialysis period when equilibration between blood and tissue
stores occurs. Long-term lithium use rarely leads to renal insufficiency and
ESRD, although renal function can improve if the drug is discontinued. Val-
proate may be used in patients with ESRD, although free valproic acid levels
need to be monitored because ESRD can result in increased free serum levels
(L. M. Cohen et al. 2004).

Antipsychotics
All antipsychotics may be used in patients with renal disease, and most do not
require a dosage adjustment, although clearance of risperidone and its metab-
olites, including paliperidone, is reduced by 60% (L. M. Cohen et al. 2004).

Benzodiazepines
Because benzodiazepines are metabolized by the liver, a dosage reduction is
generally not required, although the half-life of benzodiazepines is higher in
patients with ESRD (Wagner and O’Hara 1997).

Psychotropic Use in Liver Disease

Antidepressants
Most antidepressants undergo phase I hepatic oxidative metabolism and re-
quire dosage adjustment in patients with liver disease. Citalopram, fluoxetine,
paroxetine, and sertraline have been studied in patients with hepatitis C, usu-
ally in the setting of interferon-α treatment, and have been found safe (Rob-
inson and Owen 2005). Dosage modification depends on the severity of the
liver disease; as a general rule, patients with hepatic insufficiency should re-
ceive one-third to one-half the usual dosage for healthy patients (Robinson
and Levenson 2000).
294 Clinical Manual of Psychosomatic Medicine

Benzodiazepines
The metabolism of oxazepam, lorazepam, and temazepam are phase II depen-
dent; their clearance is less affected by liver disease, and they should therefore
be considered first if a benzodiazepine is required (Wilkinson 1978). The
clearance of other benzodiazepines is substantially reduced in patients with
liver disease because of metabolism by phase I reactions. In patients with he-
patic encephalopathy, benzodiazepines can exacerbate mental status changes,
including subclinical or latent encephalopathy (Branch 1987).

Antipsychotics
The data are sparse regarding the use of antipsychotics in patients with liver
disease, although haloperidol and the atypical antipsychotics are commonly
used (Schlatter et al. 2009). Atypical antipsychotics have been associated with
pancreatitis, most commonly with clozapine, but pancreatitis has also been re-
ported with olanzapine and risperidone (Koller et al. 2003).

Mood Stabilizers
Valproic acid and carbamazepine are relatively contraindicated in patients
with liver disease because of the risk of hepatotoxicity. Valproic acid is associ-
ated with elevated liver enzymes in acute and chronic use, and acute liver fail-
ure most often occurs within the first 6 months of treatment (Smith et al.
2008). Hyperammonemic encephalopathy has been reported even in the con-
text of normal liver enzymes, with improvement in mental status after discon-
tinuation of the drug (Wadzinski et al. 2007). Valproic acid can also cause
pancreatitis.

Nonpharmacological Treatments
Electroconvulsive Therapy
ECT is a first-line treatment for depressed patients who are severely malnour-
ished or dehydrated, who have either catatonia or psychotic depression, or
who have a previously documented good response to ECT. ECT has no ab-
solute contraindications; however, some medical conditions increase the mor-
bidity associated with ECT and require thoughtful review of the risks and
 Biological Treatments 295

benefits. These medical conditions include 1) those that cause increased in-
tracranial pressure; 2) those that increase the risk of serious hemorrhage; and
3) pathophysiological states that cause hemodynamic compromise, such as an
acute myocardial infarction or malignant arrhythmias. Cardiac complications
are the most common etiology of significant morbidity and mortality during
ECT. The addition of beta-blockers and antiarrhythmics before ECT reduces
some of these risks (Rasmussen et al. 2002a, 2002b).

Other Neuropsychiatric Treatments

For many years, ECT was the only nonpharmacological psychiatric procedure
available to treat severe or medication-refractory depression and other psychi-
atric conditions. Data are emerging regarding other forms of therapeutic brain
stimulation, such as transcranial magnetic stimulation (TMS), vagal nerve
stimulation (VNS), and deep brain stimulation (DBS). It is not in the scope of
this book to review these treatments in detail, but the consulting psychiatrist
needs to be aware of the potential psychiatric implications of VNS and DBS,
particularly in neurological patients.

Vagal Nerve Stimulation

VNS is delivered from a small pacemaker-like generator implanted in the
chest that sends preprogrammed, intermittent, mild electrical pulses through
the vagus nerve to the brain. VNS was approved by the U.S. Food and Drug
Administration in 1997 for adjunctive treatment for patients whose partial-
onset seizures are refractory to antiepileptic drugs. In 2005, VNS was ap-
proved for patients with treatment-resistant depression. Studies regarding its
effect on depressive symptoms have had mixed results, but generally have
shown that the treatment response is delayed and gradual in onset (Elger et al.
2000; Milby et al. 2008; Rush and Siefert 2009). Optimal dosing strategies
have not been determined, and clinically useful predictors of who will respond
to treatment have not been identified (Rush and Siefert 2009).

Deep Brain Stimulation

The effective use of high-frequency DBS for treatment of various neurological
diseases, particularly Parkinson’s disease, is well established. Therapeutic trials
have been conducted to examine the effectiveness of DBS in treatment-resistant
depression, obsessive-compulsive disorder, and Tourette’s disorder. Surgical tar-
296 Clinical Manual of Psychosomatic Medicine

gets for electrode placement are in the subgenual cingulate cortex for depres-
sion, the anterior internal capsule for obsessive-compulsive disorder, and the
thalamic nucleus for Tourette’s disorder. Although immediate relief of symp-
toms has been reported, a significant proportion of symptom improvement oc-
curs after months of long-term stimulation (Tye et al. 2009).

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 15
Psychosocial Management

Beyond the symptoms, signs, personality style, and medical or surgical co-
morbidities that each patient brings to a psychiatric consultation are psycho-
social elements that shape a patient’s experience of illness. These factors may
present challenges, interfere with care, or provide additional means of sup-
port, but they may not be ignored by the psychiatrist who hopes to under-
stand the patient’s dilemma and thereby advise or assist constructively.

Culture, Ethnicity, and Language

Trainees in psychosomatic medicine may feel uncertain or ill at ease during
moments when their émigré-tourist status in medical-surgical territory is ex-
posed. Their expectations, disposition, vocabulary, or goals may feel out of
place. Similarly, patients may feel that the hospital or a psychiatrist’s office is
foreign territory, particularly when their identity is shaped by distinctive cul-
tural, ethnic, and language characteristics.

Culture
Culture involves the history, traditions, expressions (whether in art, literature,
music, clothing, architecture, etc.), values, social structures, behaviors, and

301
302 Clinical Manual of Psychosomatic Medicine

achievements of a particular group of people. Cultural elements may be expan-

sive and transcend national or continental boundaries (e.g., aspects of Islamic
or Western European culture), but patients may also present with idiosyncra-
sies that reflect a select subculture shaped by vocation, age, geography, convic-
tion, or singular practices (Ahmed et al. 2007; Betancourt 2006; Hobbs 2008;
Juckett and Rudolf-Watson 2010). DSM-IV-TR (American Psychiatric Asso-
ciation 2000) recommends that a clinician consider the following facets
(Lewis-Fernandez and Diaz 2002).

• Cultural identity—the patient’s perception of cultural background, day-to-

day practices that reflect the patient’s association with a cultural group, lan-
guages spoken, language(s) preferred now (and in which settings), sense of
identifying with “mainstream” American culture (and in what practical
ways), circumstances of immigration (whether personal or ancestral), and
vocational consequences of culture, if any
• Cultural explanations—the patient’s choice of words to communicate his
or her symptoms, the meaning of those symptoms within the patient’s cul-
tural group or the family’s explanation of the symptoms, the patient’s past
experience and current expectation of consultation with a psychiatrist,
and whether the patient has sought help from alternative sources
• Psychosocial environment and function—how current stressors and symp-
toms have interfered with daily function, and what sources of social sup-
port are available within the culture
• Consequent relationship between patient and clinician—the difficulties that
the cultural and other differences (e.g., socioeconomic, educational, eth-
nic, gender) between the patient and clinician may cause in diagnosis and
treatment (e.g., limited communication because of language, understand-
ing of symptoms, discerning whether a given behavior is pathological)

Ethnicity
Ethnicity is associated with challenges in both diagnosis and treatment.

Differential Diagnosis
Differential diagnosis can be altered by ethnic propensities and prejudice.
Ethnicity may influence the timing of a patient’s presentation for medical care
 Psychosocial Management 303

(prompting a perception of more severe disease), affect a patient’s emphasis on

psychotic symptoms but denial of mood symptoms (complicating accurate
distinction between schizophrenia and bipolar disorder, for example), or
shape a physician’s bias as expressed in the choice of questions asked of the pa-
tient or family (Huang et al. 2006; McGilloway et al. 2010).

Psychopharmacology
Psychopharmacological riddles may arise from ethnic factors.
Genomics. Genetic variations in hepatic cytochrome P450 isoenzymes may
affect efficacy of treatment, side effects, therapeutic dosage requirements, and
potential drug-drug interactions. This science is in its infancy, with differing
perspectives on the evidence base for widespread clinical application (de Leon
et al. 2009; Zhou 2009a, 2009b). Nonetheless, sufficient studies have been re-
ported to warrant the need for the consultation psychiatrist to remain alert to
the possibility that unexpected clinical sensitivity (i.e., brisk development of
side effects at low doses), apparent absence of effect (i.e., absence of both ef-
ficacy and side effects despite unusually high dosages), and other apparent
pharmacokinetic aberrations (e.g., unusual reactivity to warfarin) may result
from pharmacogenomic variations that affect the metabolism of psychotropic
agents.
Herbal and alternative preparations. Individuals of some ethnic, cultural,
or religious groups may perceive herbal and alternative preparations as less
toxic (not to mention less expensive and unencumbered by the necessity of a
prescription) than medicines associated with Western medicine. Also, these
individuals may not disclose the use of these agents to conventional physi-
cians, further obscuring the diagnostic task (Feng et al. 2010; Li et al. 2004).

Language
Language Barriers
Effective communication is a skill that rewards refinement throughout a cli-
nician’s career, even when patient and physician are native to the same lan-
guage. The dismay, frustration, or even resignation that a patient or physician
might experience when confronted with a language barrier can be a substan-
tial obstacle to accurate assessment and effective care.
304 Clinical Manual of Psychosomatic Medicine

Interpreters
Interpreters are essential and invaluable when providing consultations with
individuals who speak other languages (Bauer and Alegria 2010; Diamond
and Jacobs 2010; Karliner et al. 2004). The following recommendations will
strengthen the patient-physician relationship and improve the interview yield
when an interpreter is used to bridge a language gap:

1. Avoid use of family members. Despite the convenience, patients may not
be forthcoming with family members, and family members may filter or
even falsify sensitive or embarrassing information.
2. Avoid use of nonprofessional staff. Although secretarial or other nonmed-
ical employees may be helpful in providing cultural insight, their absence
of medical training may result in inaccurate translation and a diminished
awareness of the necessity of strict confidentiality.
3. Welcome “cultural consultation” from the interpreter if time allows before
the interview. The interpreter may be able to help the psychiatrist avoid an
unnecessary cultural faux pas.
4. Speak to the patient and focus on nonverbal behavior. Although turning
to and addressing the interpreter feels natural, the psychiatrist can pre-
serve the advantage of his or her experience in assessing nonverbal com-
munication by remaining assiduously attentive to the patient.
5. Use short sentences and frequent pauses. This style decreases the risk of
distraction and helps the interpreter to avoid paraphrasing to summarize
a lengthy question.
6. Beware of colloquialisms or informal slang. The interpreter may feel ob-
ligated to provide a literal translation or may be unfamiliar with a partic-
ular expression. Similarly, the psychiatrist needs to allow the interpreter to
rephrase formal terms, such as depression, which may not have a precise
counterpart in the patient’s language.
7. Avoid jargon or technical terms. Even if translated accurately, a patient
who does not understand may not feel free to say so.
8. If treatment has been discussed, ask the patient to repeat what he or she
understands. The response serves as a comprehension check and may also
give a clue regarding the patient’s intention to follow through with the
recommendations.
 Psychosocial Management 305

9. Ask the interpreter for his or her observations and thoughts after the ses-
sion. The interpreter may have translated for the patient with several
other teams or during previous hospitalizations and may have valuable
collateral history to provide.
10. Whenever possible, use the same interpreter in subsequent visits with the
patient. This consistency can increase accuracy and trust.

Spiritual, Existential, and Religious Factors

Multiple surveys confirm that most people indicate they have a spiritual life
(Mueller et al. 2001) and that the majority of hospitalized patients express ap-
preciation for the religious and supportive attention of chaplains (Piderman et
al. 2008). Spirituality commonly involves a pursuit of transcendent meaning
or purpose, values, and an experience of connectedness. Medical illness often
accentuates these interests and moves them to the fore of a patient’s thoughts.
Although psychiatrists are less likely than either their patients or other U.S.
physicians to describe themselves as religious (Curlin et al. 2007), the consul-
tation psychiatrist misses an important opportunity to better understand the
full context of a patient’s life and better mobilize appropriate internal and ex-
ternal resources if he or she overlooks a patient’s perspective on spiritual mat-
ters (Galanter 2010). The goal is not to intrude on the patient’s questions with
either conviction or skepticism, but rather to elicit the patient’s feelings and
thoughts in a manner that reinforces the patient’s experience of having been
heard and, thereby, encourages the patient to seek further appropriate re-
sources. The following questions may inform a patient that a psychiatrist re-
spects and hopes to better understand this dimension of the patient’s life
(Breitbart 2002; Grossman et al. 2005; Puchalski and Romer 2000):

1. Do you see yourself as a spiritual or religious person?

2a. (If no) Has that always been so, or have your beliefs and/or practice
changed over time?
2b. (If yes) For you, is this a personal, private exercise? Are you part of a spir-
itual or religious community?
3. If you identify with a particular religious community, how does this com-
munity support you?
4. Has spirituality or religion helped you? How? Or hurt you in any way? How?
306 Clinical Manual of Psychosomatic Medicine

5. How important are your religious or spiritual beliefs to you now?

6. How might those beliefs influence your choices or behavior during this
illness?
7. Are you at peace? (Steinhauser et al. 2006)
8. How would you like me to help address these issues in your care?
9. Would you appreciate the opportunity to visit with a hospital chaplain?

Patient’s Practical Concerns

Practical concerns may weigh on a patient’s mind, influence his or her will-
ingness to consider diagnostic and treatment options, moderate adherence to
recommendations, and possibly determine long-term outcome. In the hospi-
tal, these issues may be addressed by the primary team or a social worker; how-
ever, in outpatient consultation or in situations where a patient perceives that
the hospital team’s focus is solely on medical or surgical issues, these concerns
may not receive optimal attention unless the psychiatrist opens the subject.

Financial Worries
Financial worries may be elicited by questions such as the following:

1. Do you spend time thinking about your financial affairs or stressors most
days?
2. Have you looked for or taken on additional work to ease your financial
situation?
3. Are there other people (e.g., aging parents, unemployed child or relative)
who depend on you for financial support?
4. Have you chosen to postpone medical care or decided to stop a medica-
tion in the past because of cost?

Safety
Safety may be compromised for multiple reasons, with or without the patient’s
awareness. The patient’s initial hospital presentation may have resulted from
an injury or illness that alerts medical staff to a particular safety risk; at other
times, the underlying problem remains obscure unless deliberately pursued.
 Psychosocial Management 307

Domestic Abuse or Violence

The psychiatrist should interview the patient without family members present
and broach the subject of domestic abuse or violence in a respectful, gentle
tone that avoids arousing shame and subsequent silence.

Incapacity
Insidious but progressive cognitive decline (or the burden of caring for a part-
ner with debilitating dementia), decreasing mobility and independence by
virtue of age and dwindling vigor, or a confluence of psychosocial stressors
may render an individual increasingly isolated and incapable of making effec-
tive decisions in his or her own best interest. The psychiatrist may need to ac-
tivate necessary medical, family, community, or legal resources to clarify the
patient’s situation and explore alternative living arrangements.

Postconsultation Care
Physicians are on familiar ground in the hospital, but most patients are not.
They may not understand the role of different teams or different members of
the same team; they may be confused and feel less secure about their care when
a particular physician appears to vanish without a word; the lexicon of medi-
cine may be foreign and important questions occur only after the consulting
team has left the room. The psychiatrist can improve the patient’s confidence
and lower anxiety by addressing the following:

• The role of the consultation team and its various members

• Communication between successive team members if a rotation will in-
troduce a change for the patient
• Subsequent follow-up:
– Guidance regarding psychotropic adjustments or termination. To avoid ei-
ther an inadequate trial or the risk of ongoing use of a psychotropic that
may require only time-limited use, consider printing a patient educa-
tion information sheet about the relevant medication(s) and briefly an-
notating it with the same recommendations given to the primary
medical-surgical team caring for the patient.
308 Clinical Manual of Psychosomatic Medicine

– Psychiatric follow-up. Clarify for the patient if his or her diagnosis and
treatment plan warrant psychiatric follow-up or if follow-up from a
primary care physician will be appropriate and sufficient.
– Community resources. When community resources are available, spec-
ify the particular resources and tell the patient how to access the help;
be realistic about possible obstacles, waiting lists, and other issues.

Promoting Resilience Rather Than Vulnerability

Demoralization is common among patients in the general hospital and is often
mistaken for depression, with which demoralization may share features. The hall-
mark of demoralization consists of a subjective appraisal of one’s own impotence;
typically, the multiple or prolonged uncertainties of medical illness so deplete an
individual that he or she loses confidence in his or her capacity to endure. Feelings
of worthlessness and hopelessness may follow, but when the tide of adversity is
turned, patients who feel demoralized can recapture hope, confidence, and pur-
pose much more rapidly than can patients with severe depression.
Griffith and colleagues (Griffith and Gaby 2005; Griffith and Griffith
2002) have proposed a helpful and practical schema of eight existential pos-
tures (Table 15–1). A healthy person may enjoy a position of resilience in all or
most of these domains, whereas a patient oppressed by illness may slip toward
the opposing pole of vulnerability. The psychiatrist has an opportunity to iden-
tify what themes of vulnerability dominate a patient’s perception of his or her
illness, and to structure the interview to help the patient move instead toward
postures of greater resilience. The eight existential postures and suggested ques-
tions listed in the table are intended as instruments of respectful inquiry, not
exhortation (Griffith and Gaby 2005; Griffith and Griffith 2002). The reader
is strongly encouraged to consult the source material, in which each question is
further explained and illustrated with clinical examples.

Additional Supportive Tools

Additional supportive tools, including education, psychotherapy, hypnosis,
and relaxation, can be used to help a patient manage the trials and tensions
that emerge when medical and surgical problems disrupt life.
 Psychosocial Management 309

Education
Education need not be formal, comprehensive, or physician delivered to play
an important part in easing a patient’s experience of alienation and fear in the
medical arena.

Hospital Bedside
At the hospital bedside, the psychiatrist may observe that a patient’s distress is
aggravated by ignorance, inaccurate assumptions, distorted communication,
or a limited coping reservoir. Remaining aware that information alone may in-
crease anxiety and stress for some patients, the therapist may use the bedside
consultation for the following functions:

• Informing the patient who is unaware of the procedure involved in a

forthcoming diagnostic test, or translating a medical acronym the patient
heard as the team discussed his or her situation in rounds
• Correcting misunderstandings or perhaps public prejudice regarding par-
ticular medical or psychiatric conditions
• Affirming permission for the patient to pose particular questions to his or
her primary physician, or offering practical tips to improve communica-
tion and reinforce a sense of participation with the primary team
• Illustrating a coping technique, such as reframing or distraction, that the
patient might use to help endure a noxious procedure or a setback in clin-
ical prognosis

Outpatient Setting
In the outpatient setting, educational intervention and support more com-
monly occur in group settings and are often organized according to disease
(e.g., pulmonary disease, diabetes mellitus) or treatment (e.g., organ trans-
plantation, radiation therapy). Elements of effective group psychoeducation
include the following:

• Accurate medical knowledge and associated management tips

• Recognition of the emotional challenges common to most patients who
are adjusting to the disease and encouragement of mutual expression to re-
duce individual isolation
310 Clinical Manual of Psychosomatic Medicine

Table 15–1. Existential postures: themes of resilience versus

vulnerability
Coherence Versus Confusion

• How do you make sense of what you are going through?

• When you are uncertain, how do you deal with moments of feeling confused?
• To whom do you turn for help when you feel confused?
• To whom do you turn for help when you feel confused?
Communion Versus Isolation
• Who really understands your situation?
• When you have difficult days, with whom do you talk?
• In whose presence do you feel a bodily sense of peace?
Hope Versus Despair
• From what sources do you draw hope?
• On difficult days, what keeps you from giving up?
• Who have you known in your life who would not be surprised to see you hopeful
despite adversity?
• What did this person understand about you that we do not know?
Purpose Versus Meaninglessness

• What keeps you going on difficult days?

• For whom, or for what, does it matter that you continue to live?
• What is your best sense as to what your life is about and how this illness fits in it?
• What do you hope to contribute with your life in whatever time you have
remaining? (for the terminally ill patient)
Agency Versus Helplessness
• What is your prioritized list of concerns? What concerns you most?
• What most helps you to stand strong against the challenges of this illness?
• What should I know about you as a person that lies beyond your illness?
• How have you kept this illness from taking charge of your entire life?
 Psychosocial Management 311

Table 15–1. Existential postures: themes of resilience versus

vulnerability (continued)
Courage Versus Cowardice

• Have there been moments when you felt tempted to give up but didn’t? How did
you make a decision to persevere?
• If you saw someone else taking such a step even though feeling afraid, would you
consider that an act of courage?
• Can you imagine viewing yourself as courageous? Is that a description of yourself
you would desire?
• Can you imagine that others who see how you are coping with this illness might
describe you as courageous?
Gratitude Versus Resentment

• For what are you most grateful?

• Are there moments when you can still feel joy despite the sorrow you have been
through?
• What sustains your capacity to experience joy in the midst of pain?
• If you could look back on this illness from some future time, what would you say
that you took from the experience that added to your life?
Trust Versus Fear

• Who has given you a shoulder to lean on?

• Who relies on you? How did he or she first decide to trust you?

Source. Adapted with permission from Griffith JL, Gaby L: “Brief Psychotherapy at the Bed-
side: Countering Demoralization From Medical Illness.” Psychosomatics 46:109–116, 2005.

• Collaborative support and strategies to reinforce adherence to treatment

regimens that may be demanding or have unpleasant side effects
• The experience of giving to one another, which provides a tonic infusion
of refreshed purpose and meaning for individuals whose illness has left
them feeling impotent and dependent

Psychotherapy
Psychotherapy involves a relationship and the psychiatrist’s effort to see the
world through the patient’s eyes. Even brief inpatient encounters can either
312 Clinical Manual of Psychosomatic Medicine

serve and advance these goals or erode connection and hope. More formal,
structured psychotherapy with medically ill patients is most often conducted
in an outpatient setting.

Group Psychotherapy
Group psychotherapy, like psychoeducational groups, is most frequently or-
ganized according to type of illness, age group, or treatment modality. Regard-
less of the common ground shared by the patients, group processes give
patients important opportunities for the following:

• Emotional expression—Shared expression in a group can reduce isolation and

moderate the intensity of emotion shared with a spouse or family members.
• Social support—Patients have often experienced social losses as a conse-
quence of illness; group psychotherapy can form the nidus for a new social
network.
• Shared coping strategies and resources—Patients can learn a great deal from one
another and may award peers with singular credibility and understanding.

Individual Therapy
Individual therapy, whether brief and focused or open-ended with evolving
goals, may be largely supportive, interpersonal, or psychodynamic, depending
on the unique circumstances of each patient. The patient’s and clinician’s
choice of therapy includes consideration of the following:

• Disease characteristics—acute versus chronic, indolent versus life threaten-

ing, consequent disruptions in function (e.g., mobility, vocational, sex-
ual), potential lifestyle modifications necessary
• Psychiatric history—previous anxiety or depression, illness-related experi-
ences, family history
• Goals—for example, management of acute symptoms only versus resolv-
ing conflict at home or work brought to the fore by illness versus adjust-
ment to major reorganization of life and priorities

Cognitive-Behavioral Therapy
Cognitive-behavioral therapy, provided in either group psychoeducational
formats or in individual sessions that allow greater focus on each patient’s sit-
 Psychosocial Management 313

uation and symptoms, has earned a broad evidence base for efficacy in reduc-
ing anxiety and depression (Hollon and Ponniah 2010; Zinbarg et al. 2010).

Family Therapy
Family therapy, although not often used, is a useful adjunct when a patient’s
diagnosis may force significant role changes, introduce new financial stressors,
exhaust family caregivers, unmask prior dysfunction, or pose an imminent
loss (Hartmann et al. 2010).

Hypnosis and Relaxation

Hypnosis is limited by the relative paucity of experienced and certified practi-
tioners, the time commitment necessary, and the fact that a minority of pa-
tients (perhaps 25%) are able to fully engage in the process. However, a broader
range of patients can be taught relaxation strategies and may, with diligent rep-
etition, enable themselves to achieve deep relaxation that can provide adjunc-
tive relief or assistance in situations in which hypnosis has also been successfully
applied (Patterson and Jensen 2003; Surman and Baer 2008). Hypnosis and/or
relaxation may be beneficial for patients experiencing the following:

• Nausea and vomiting—By recruiting an intensified focus away from the

sensations and thoughts associated with nausea (i.e., displacing nausea
from the patient’s center stage of awareness), hypnosis and/or relaxation
helps to diminish the symptom and interrupt a behavioral cycle (Miller
and Whorwell 2009).
• Pain—Similarly, through hypnosis and/or relaxation, pain is relegated to
the periphery of a patient’s awareness, enabling the patient to deliberately
replace the sensation with a more relaxing image or focus of attention. Al-
though pain is not ablated, a patient may tolerate procedures more easily
with less analgesic requirement (Lang et al. 2000; Stoelb et al. 2009).
• Anxiety—The benefit of hypnosis and/or relaxation is further enhanced
when nausea or pain has exacerbated anxiety.
• Problems with compliance and control—To the extent that procedural pain
or anxiety has impeded patient adherence to recommended diagnostic or
therapeutic measures, hypnosis and/or relaxation can facilitate a successful
outcome; this tool has the further advantage of providing the patient some
sense of control over his or her circumstances.
314 Clinical Manual of Psychosomatic Medicine

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ders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Associ-
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use on the quality of psychiatric care: a systematic review. Psychiatr Serv 61:765–
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teaching clinicians how to overcome language barriers to health care. J Gen Intern
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and mental disorders in community-living Asian older adults. Arch Gerontol
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 Psychosocial Management 315

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 PA R T I V

Unique Issues in
Psychosomatic Medicine Settings
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 16
Bariatric Surgery

T he number of bariatric surgical procedures performed in the United States

has steadily increased. Several factors have contributed to this increase (Col-
lazo-Clavell et al. 2006):

• The prevalence of extreme obesity continues to increase.

• Medical therapies for obesity have limited effectiveness.
• Weight loss after bariatric surgery has demonstrated positive effects on
obesity-related medical complications. Benefits of surgery usually out-
weigh risks when there are at least partially remediable obesity-related
medical complications in a reasonably suitable surgical candidate. Many
measures of psychological and physical functioning convincingly improve
after bariatric surgery (Powers and Santana 2011).

Types of Bariatric Surgery

Restrictive Procedure
A small pouch is created at the top of the stomach. Restrictive procedures in-
clude vertical-banded gastroplasty and adjustable gastric banding. Both proce-
dures produce less dramatic weight loss over time than combination procedures.

319
320 Clinical Manual of Psychosomatic Medicine

Combined Restrictive and Malabsorptive Procedure

The most commonly performed combination procedures include biliopan-
creatic diversion and the Roux-en-Y gastric bypass. Roux-en-Y gastric bypass
is the most frequently performed bariatric surgery in the United States (Miller
and Smith 2006), accounting for 80% of bariatric procedures (Adams et al.
2007). By bypassing the lower stomach and a majority of the small intestine,
pH changes and malabsorption occur. Patients are at risk for nutrient defi-
ciencies and require supplementation postoperatively. The surgery also has
significant effects on drug absorption.

Criteria for Bariatric Surgery

No criteria have been published that completely address all of the complicated
factors that must be collectively weighed before a patient gives informed con-
sent for bariatric surgery. Bariatric surgery is never either risk-free or unques-
tioningly effective. Generally accepted guidelines (Collazo-Clavell et al. 2006;
National Institutes of Health 1991) include the following:

• High body mass index (i.e., BMI≥40, or >35 if two or more serious re-
mediable complications are present)
• Presence of obesity-related medical complications (e.g., diabetes, arthrop-
athy, obstructive sleep apnea, stroke, cardiovascular disease)
• Documented or high probability of failure of nonsurgical weight loss in-
terventions
• Demonstrated motivation and adherence
• High level of education about risks and benefits and ability to give in-
formed consent

Medical Assessment of
the Potential Bariatric Surgery Patient

1. Obtain comprehensive weight and nutrition history. Domains include

current dietary habits, current physical activity, exercise habits, previous
 Bariatric Surgery 321

weight loss efforts, medical treatments, duration of weight loss mainte-

nance, and obstacles to successful weight loss maintenance.
2. Identify obesity-related medical comorbidities
3. Identify medical comorbidities that might affect surgical risk. Bariatric
surgery has few absolute medical contraindications. Certainly, patients
who cannot give informed consent because of disabling cognitive impair-
ment and patients who have advanced liver disease with portal hyperten-
sion would not qualify as surgical candidates (Collazo-Clavell et al.
2006). Unstable coronary artery disease and uncontrolled severe obstruc-
tive sleep apnea cause great concern as well, particularly if accompanied
by other medical risks.
4. Identify medical causes of obesity (e.g., thyroid disorder, Cushing’s syn-
drome).
5. Identify medications that may promote weight gain (especially antipsy-
chotics, mood stabilizers, and antidepressants).
6. Review family history of obesity.
7. Identify harmful lifestyle habits (e.g., smoking, alcohol use, illicit drug
use).

Psychiatric Assessment of
the Potential Bariatric Surgery Patient
Lack of Evidence-Based Evaluative Models
or Consensus Guidelines
No evidence-based evaluative models or consensus guidelines currently exist
to guide psychiatric evaluation of bariatric surgery candidacy. Different cen-
ters have different methodologies and thresholds (Fabricatore et al. 2006;
Marcus et al. 2009). In practice, most centers would list only a few absolute
psychiatric contraindications for bariatric surgery. Most centers would in-
clude the following (Bauchowitz et al. 2005):

• Active alcohol abuse

• Inability to maintain adherence to medical treatments and medications
• Active anorexia or bulimia nervosa
322 Clinical Manual of Psychosomatic Medicine

• Significant current suicidality or self-harm impulses requiring psychiatric

hospitalization
• Severe personality disorder
• Active psychosis
• Current manic episode
• Inability to provide informed consent

Negative Effects of Presurgical Psychiatric Disorders

on Postsurgical Weight Loss
The presence of presurgical psychiatric disorders negatively impacts postsur-
gical weight loss. Recent psychiatric hospitalization and the presence of a psy-
chiatric disorder have each been associated with suboptimal weight loss after
surgery (Herpetz et al. 2004; Kinzl et al. 2006). Bariatric surgery candidates
who have two or more psychiatric diagnoses have significantly less postsurgi-
cal weight loss than patients with one or no psychiatric disorder (weight loss of
10.8, 14.0, and 16.0 BMI units, respectively, P=0.047; Kinzl et al. 2006). Of-
ten, the recommendation is to delay surgery until a psychiatric disorder or be-
havioral disturbance is more stable or better managed.

High Rates of Psychiatric Disorders Among

Bariatric Surgery Candidates
High rates of psychiatric disorders exist among bariatric surgery candidates. Up
to 70% of patients referred for weight loss surgery have a lifetime history of a
psychiatric disorder, and up to 50% have a current psychiatric disorder (Black
et al. 1992; Herpetz et al. 2004; Kalarchian et al. 2007; Mauri et al. 2008;
Rosenberger et al. 2006; Rosik 2005; Sarwer et al. 2005). Half are taking psy-
chotropic medications at the time of presurgical evaluation (Pawlow et al.
2005). The following are the most common psychiatric diagnoses:

• Major depressive disorder

• Generalized anxiety disorder
• Posttraumatic stress disorder
• Obsessive-compulsive disorder
• Social anxiety disorder
• Substance use disorder
 Bariatric Surgery 323

• Binge-eating disorder
• Night eating syndrome
• Somatoform disorders

Psychological Issues That May Be Associated

With Poor Outcomes
Some specific psychological issues may be associated with poor outcomes. Al-
though no level 1 evidence is available yet, case series, case reports, and expert
consensus all strongly suggest that the following psychosocial factors predict
suboptimal postsurgical weight loss and psychological adjustment (Black et al.
1992; Herpetz et al. 2004; Rosik 2005; Sarwer et al. 2005):

• Binge eating pattern.

• Night eating pattern.
• History of past or current physical, sexual, or emotional abuse that is asso-
ciated with a positive aspect of obesity (i.e., avoidance of intimacy). History
of childhood maltreatment is associated with elevated risk for psychiatric
hospitalization after gastric bypass. Patients who derive positive psycholog-
ical benefit from obesity related to abuse history need to be identified and
treated with psychotherapy (Clark et al. 2007).
• Nonadherence to medical, medication, and nutritional advice. Demon-
strating that behavioral changes can be made prior to surgery, even if
weight is not actually lost preoperatively, improves patient confidence that
the changes can be maintained after surgery.

Elements of Psychiatric Evaluation of

a Bariatric Surgery Candidate
At least 20% of patients being evaluated for weight loss surgery have active
psychiatric illness that should be addressed prior to proceeding with bariatric
surgery (Wildes et al. 2008; Zimmerman et al. 2007). The following clinical
domains are derived from reported reasons for recommending surgery deferral
for psychiatric reasons:

• Current and past psychiatric diagnoses and treatments, especially of

mood, eating, anxiety, substance use, and personality disorders.
324 Clinical Manual of Psychosomatic Medicine

• Psychiatric predisposition (i.e., family history, past history).

• Medical history, including potential toxic or metabolic contributors to
psychiatric symptoms and signs.
• Nutritional and weight loss history, including self-described barriers to
maintenance of weight loss in the past.
• Eating patterns, focusing on history of binge eating, night eating, and
image of food as comforting. Questions about a patient’s capacity to self-
soothe, relax, and manage stress should be included.
• Current and past physical, emotional, or sexual abuse history, along with
documentation about whether the patient derives positive psychological
benefit to being overweight. Questions about intimacy and desire for in-
timacy are important and appropriate. Up to 66% of bariatric surgery can-
didates report childhood history of emotional, sexual, or physical abuse
(Wildes et al. 2008). History of childhood maltreatment is associated with
risk for psychiatric hospitalization after gastric bypass (Clark et al. 2007).
• Evidence for adherence and nonadherence to medical, medication, and
nutritional advice.
• Assessment of locus of control. A patient with an external locus of control
may minimize his or her view that he or she can exert significant influence
on outcome of weight loss attempts, including surgery. For example, the
patient may minimize the roles of physical exercise, nutrition-related be-
havioral changes, and social support.
• Documentation of available supports, including both perioperative phys-
ical assistance and postoperative sources of emotional support.
• Lifestyle considerations, including physical activity, eating habits of others
in the house, smoking, and alcohol and drug use patterns.
• Current medications. After surgery, a patient may experience changes in
absorption and distribution of medications, including, and perhaps espe-
cially, psychotropic medications.
• Careful mental status examination. The psychiatrist must establish that
the patient’s self-harm risk is low and that the patient has sufficient cog-
nitive capacity to provide informed consent.
 Bariatric Surgery 325

Presurgical Psychiatric Management

1. Optimally manage psychiatric disorders. In the Mayo Clinic integrated bar-
iatric surgery practice (Collazo-Clavell et al. 2006), patients must not
have had psychiatric hospitalization for 12 months prior to surgery. Also,
for patients with a diagnosed substance use disorder, 12 months of absti-
nence must be documented before surgery proceeds.
2. Document completion of indicated psychotherapy interventions. In the Mayo
Clinic bariatric surgery practice, patients are required to have documenta-
tion of successful completion of psychotherapy by a licensed mental health
professional for identified psychosocial barriers to postsurgical confidence
in ability to maintain weight loss (Collazo-Clavell et al. 2006). The con-
tent of most psychotherapy focuses on trauma survivorship issues, adher-
ence issues, extreme internal locus of control, and difficulties with impulse
control that lead to stress eating and night eating.
3. Prescribe behavioral and lifestyle interventions that build patient confidence
that postsurgical weight loss can be maintained. To assess motivation, pre-
dict adherence to postsurgical recommendations, and build confidence in
providers and patients, some programs mandate that patients achieve be-
havioral milestones (and sometimes actual weight loss) prior to surgery.
Although no published randomized controlled trial has examined the
benefits of receiving behavioral therapy before bariatric surgery with re-
gard to postsurgical weight loss, some programs require completion of
presurgical behavioral structured interventions that focus on improved
nutrition, eating patterns, social support, exercise, and stress manage-
ment. Patients are told that making necessary lifestyle and eating pattern
changes before surgery should give them increased confidence they can
maintain those necessary changes postoperatively.
4. Consider presurgery psychotropic medication drug levels. Drug solubility and
surface area for absorption are affected by gastric bypass:
• Potential for reduced drug absorption. Reductions in the amount of
functioning gastrointestinal tract lead to reduced drug bioavailability
326 Clinical Manual of Psychosomatic Medicine

because of decreased surface area for drug absorption and reduced

transit time (Miller and Smith 2006).
• Reduced solubility of drugs. The solubility of drugs is affected by pH.
Drugs that are more soluble in an acidic pH are absorbed in the stom-
ach, and those soluble in alkaline environments are absorbed in the
small intestine. The solubility of both types of drugs is affected by gas-
tric bypass.

Perioperative Psychiatric Management

During the perioperative period, consulting psychiatrists should watch for evi-
dence of changes in the effects of psychotropic medications, due to absorptive
and metabolic changes that occur as a result of bypass procedures. Ensuring
ongoing availability of sources of social support and providing supportive psy-
chotherapy may be important for helping some patients. Other reasons for
psychiatric consultation during the perioperative period include delirium
management and pain control.

Postoperative Psychiatric Management

1. Make postoperative support groups and individual psychotherapy available.

Psychological issues may not have been completely resolved during pre-
operative psychotherapy, or may reemerge with body image changes pre-
cipitated by postsurgical weight loss.
2. Follow patients as indicated. Even with optimal preoperative psychiatric
management, this patient population has an elevated baseline level of psy-
chiatric illness and will frequently have psychiatric disorders recur post-
operatively.
3. Consider postoperative psychotropic medication drug levels. In the postop-
erative periods, absorptive area losses and pH changes may affect bio-
availability and absorption of medications, including psychotropic med-
ications. With metabolic changes and adipose tissue loss come the pos-
sibilities for changes in volume of distribution and in amounts of drugs,
particularly lipophilic drugs, stored in body fat. At the Mayo Clinic, psy-
chotropic medication levels are routinely measured 1 week before surgery
 Bariatric Surgery 327

and again 1 and 12 months after surgery, even if blood has to be sent out
to specialty laboratories. Medication dosage changes are sometimes re-
quired postoperatively.
4. Change extended-release preparations to regular-release formulations. Many
psychotropic medications are available in extended-release preparations
and therefore have long absorptive phases. Because of the large loss of sur-
face area for absorption and reduced transit time, extended-release medi-
cations have even greater likelihood of being affected by bypass procedures
than do regular-release preparations (Miller and Smith 2006). Liquid or
orally disintegrating tablet versions of drugs, if available, are likely to be
better absorbed.

References
Adams TD, Gress RE, Smith SC, et al: Long-term mortality after gastric bypass sur-
gery. N Engl J Med 357:753–761, 2007
Bauchowitz AU, Gonder-Frederick LA, Olbrisch ME, et al: Psychosocial evaluation of
bariatric surgery candidates: a survey of present practices. Psychosom Med
67:825–832, 2005
Black DW, Goldstein RB, Mason EE: Prevalence of mental disorder in 88 morbidly
obese bariatric clinic patients. Am J Psychiatry 149:227–234, 1992
Clark MM, Hanna BK, Mai JL, et al: Sexual abuse survivors and psychiatric hospital-
ization after bariatric surgery. Obes Surg 19:465–469, 2007
Collazo-Clavell ML, Clark MM, McAlpine DE, et al: Assessment and preparation of
patients for bariatric surgery. Mayo Clin Proc 81 (suppl):S11–S17, 2006
Fabricatore AN, Crerand CE, Wadden T, et al: How do mental health professionals
evaluate candidates for bariatric surgery? Obes Surg 16:567–573, 2006
Herpetz S, Kielmann R, Wolf AM, et al: Do psychosocial variables predict weight loss
or mental health after obesity surgery: a systematic review. Obes Res 12:1554–
1569, 2004
Kalarchian MA, Marcus MD, Levine MD, et al: Psychiatric disorders among bariatric
surgery candidates: relationship to obesity and functional health status. Am J Psy-
chiatry 164:328–334, 2007
Kinzl JF, Schrattenencker M, Traweger C, et al: Psychosocial predictors of weight loss
after bariatric surgery. Obes Surg 16:1609–1614, 2006
Marcus MD, Kalarchian MA, Courcoulas AP: Psychiatric evaluation and follow-up of
bariatric surgery patients. Am J Psychiatry 166:285–291, 2009
328 Clinical Manual of Psychosomatic Medicine

Mauri M, Rucci P, Calderone A, Santini F, et al: Axis I and II disorders and quality of
life in bariatric surgery candidates. J Clin Psychiatry 69:295–301, 2008
Miller AD, Smith KM: Medication and nutrient administration considerations after
bariatric surgery. Am J Health Syst Pharm 63:1852–1857, 2006
National Institutes of Health Consensus Development Conference Panel: NIH Con-
ference: gastrointestinal surgery for severe obesity. Ann Intern Med 115:956–
961, 1991
Pawlow LA, O’Neill PM, White MA, et al: Findings and outcomes of psychological
evaluations of gastric bypass applicants. Surg Obes Relat Dis 1:523–527, 2005
Powers PS, Santana CA: Surgery, in The American Psychiatric Publishing Textbook of
Psychosomatic Medicine, 2nd Edition. Edited by Levenson JL. Washington, DC,
American Psychiatric Publishing, 2011, pp 691–724
Rosenberger PH, Henderson KE, Grilo CM: Psychiatric disorder comorbidity and asso-
ciation with eating disorders in bariatric surgery patients: a cross-sectional study us-
ing structured interview-based diagnosis. J Clin Psychiatry 67:1080–1085, 2006
Rosik CH: Psychiatric symptoms among prospective bariatric surgery patients: rates of
prevalence and their relation to social desirability, pursuit of surgery, and follow-
up attendance. Obes Surg 15:677–683, 2005
Sarwer DB, Wadden TA, Fabricatore AN: Psychosocial and behavioral aspects of bar-
iatric surgery. Obes Res 13:639–648, 2005
Wildes JE, Kalarchian MA, Marcus MD, et al: Childhood maltreatment and psychi-
atric morbidity in bariatric surgery candidates. Obes Surg 18:306–313, 2008
Zimmerman M, Rancione-Witt C, Chelminski I, et al: Presurgical psychiatric evalu-
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quency of exclusion. J Clin Psychiatry 68:1557–1562, 2007
 17
Cardiology

Cardiovascular disease (CVD) is highly prevalent in the general population.

The lifetime risk at age 40 is one in two for men and one in three for women
(Lloyd-Jones et al. 1999). The relationship between CVD and psychiatric ill-
ness is complex: psychosocial factors have effects on the cardiovascular system,
and cardiac disease influences psychiatric symptoms. Depression is associated
with the development of CVD and predicts cardiac hospital admissions and
death, as well as increased health care costs and utilization of services; how-
ever, mental health treatment has not been shown to change cardiac out-
comes. Given the prevalence of CVD, the psychosomatic medicine psychia-
trist must be aware of the interrelationship of psychiatric illness and CVD and
recognize the potential impact of psychiatric interventions on the cardiovas-
cular system (Shapiro 2011).

Relationship Between Depression and

Cardiovascular Disease
Prevalence of Comorbidity
The prevalence rates of depression in patients with CVD range from 17% to
27% (Evans et al. 2005).

329
330 Clinical Manual of Psychosomatic Medicine

Depression and Increased Risk for Onset

of Cardiovascular Disease
Substantial evidence demonstrates that depression is associated with an elevated
risk for the development of CVD in initially healthy individuals. The effect sizes
range from 1.5 to 2.7 depending on the definition of CVD and the measure of de-
pression, with major depression a stronger predictor than depressive mood (Lett et
al. 2004; Rugulies 2002; Wulsin and Singal 2003). Depression is often described
as a “cardiac risk factor,” but caution is advised in using this terminology because
it can imply a causal relationship. Although the evidence is robust that depression
is correlated with the incidence of CVD, whether depression may reflect preclin-
ical cardiac disease is unknown (Frasure-Smith and Lespérance 2010).

Depression Independently Associated

With Poor Prognosis
Depression predicts morbidity and death in patients with existing CVD, and
this relationship remains significant after statistical adjustment for covariates
reflecting cardiac disease severity. For patients with stable CVD, both anxiety
and depression have been shown to predict greater major cardiac events at
2-year follow-up (Frasure-Smith and Lespérance 2008).

Myocardial Infarction
A number of studies have examined the relationship of depression and outcome
in patients after myocardial infarction (MI); the majority of the studies have
demonstrated increased mortality (Carney et al. 2003; Frasure-Smith et al.
1993; Lett et al. 2004). Among hospitalized patients following MI, major de-
pression predicts mortality at 6 months and its impact is at least equivalent to
that of left ventricular dysfunction and a history of previous MI (Frasure-Smith
et al. 1993). The risk of death is four times greater for depressed patients than for
nondepressed control patients (Frasure-Smith et al. 1993), and patients 5 years
after acute MI who were depressed during the time of admission have a greater
than 3.5-fold increased risk of cardiac death (Lespérance et al. 2002).

Congestive Heart Failure

Depression is associated with an increased incidence of congestive heart failure in
patients with coronary artery disease, regardless of antidepressant treatment (May
 Cardiology 331

et al. 2009), and depression predicts long-term mortality in patients with comor-
bid congestive heart failure and atrial fibrillation (Frasure-Smith et al. 2010).

Cardiac Surgery
Compared with cardiac coronary bypass graft surgery patients without depression,
patients who have moderate to severe depression at baseline or persistent depres-
sion 6 months after the surgery have more than a twofold increase in mortality in-
dependent of the number of grafts, diabetes, smoking, left ventricular ejection
fraction, and previous MI (Blumenthal et al. 2003). Depression also predicts mor-
tality in patients who undergo cardiac valve surgery (Ho et al. 2005).

Comorbidity Mechanisms
A number of mechanisms linking depression to CVD have been proposed, al-
though none of the factors individually provides an explanation for the asso-
ciation. If CVD and depression are causally related, it is likely to be multifac-
torial (Frasure-Smith and Lespérance 2010).

Nonadherence
Depressed patients are less likely to adhere to treatment recommendations, and
nonadherence to treatment and recommended lifestyle changes are associated
with worse cardiac outcomes (Horwitz et al. 1990; McDermott et al. 1997).

Shared Risk Factors

A number of factors have been identified with an increased risk of CVD; these
include smoking, hypertension, obesity, and high levels of alcohol consump-
tion. Depressed individuals are more likely than nondepressed individuals to
have one or more of these risk factors, and therefore the link between CVD
and depression could be due to shared risk factors (Blumenthal et al. 2003;
Joynt et al. 2003; Lett et al. 2004).

Platelet Activity
Platelets play an important role in the development of atherosclerosis and acute
coronary syndromes, and depression has been linked to increased platelet activa-
tion and hypercoagulability (Kop et al. 2002; Musselman et al. 1996).
332 Clinical Manual of Psychosomatic Medicine

Hypothalamic-Pituitary-Adrenal and
Sympathoadrenal Activation
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with
depression, and HPA axis hyperactivity augments sympathoadrenal hyperactiv-
ity, manifested by elevated plasma norepinephrine. HPA and sympathoadrenal
hyperactivity may promote the development of CVD and worsen prognosis
(Joynt et al. 2003).

Autonomic Nervous System Dysfunction

The association between impaired autonomic function and depression among
CVD patients has been demonstrated, and decreased heart rate variability is a
risk factor for sudden death and ventricular arrhythmias in patients with CVD
(Kleiger et al. 1987). Evidence suggests an association between depression and
decreased heart rate variability (Carney et al. 2001); the decreased heart rate
variability partially mediates the effect of depression on increased mortality af-
ter MI (Carney et al. 2005), although not all studies support a correlation
(Gehi et al. 2005).

Inflammation
Depressed patients with or without CVD have elevated plasma levels of in-
flammatory markers. An accelerated inflammatory response may contribute
to CVD, or CVD may induce physiological changes that result in depression
(Joynt et al. 2003; Kop et al. 2002).

Anxiety
Prevalence
Anxiety has not been studied as extensively as depression, but anxiety symp-
toms appear to be elevated in patients with acute coronary disease, and anxiety
occurs in 5%–10% of patients with chronic CVD (Frasure-Smith and Les-
pérance 2008; Sullivan et al. 2010). Although anxiety is often underdiagnosed
in hospitalized patients, some evidence suggests that anxiety is better recog-
nized than depression by the medical staff in patients after MI (Huffman et al.
2006).
 Cardiology 333

Association With Reduced Adherence

Anxiety is associated with reduced adherence to many risk-reducing recom-
mendations after MI, particularly smoking cessation (Kuhl et al. 2009).

Predictive Value of Cardiac Mortality

Some data suggest that anxiety is a predictor of cardiac morbidity and mor-
tality, but, overall, the evidence is much stronger linking depression and in-
creased cardiac mortality than anxiety (Eaker et al. 2005; Frasure-Smith and
Lespérance 2008; Meyer et al. 2010; Phillips et al. 2009).

Atypical Chest Pain and Palpitations

Atypical chest pain and palpitations commonly occur in patients who have
psychiatric illness, including panic disorder, somatoform disorders, or depres-
sion. Characteristics predictive of a diagnosis of panic disorder in patients
with chest pain include absence of coronary artery disease, atypical chest pain
quality, female sex, younger age, and high self-reported anxiety (Huffman and
Pollack 2003).

Special Issues
Implantable Cardioverter-Defibrillator
Studies examining psychopathology and quality of life after implantable car-
dioverter-defibrillator placement have increased in recent years, although the
results have been contradictory (Bostwick and Sola 2007). Avoidance and
nonspecific somatic worry can develop, and new-onset panic disorder and
posttraumatic stress disorder have been reported. Preimplantation psycholog-
ical variables, such as history of depression, trait anxiety, and dispositional op-
timism, may account for as much of the variance in quality of life outcomes as
do ejection fraction and age (Sears et al. 2005). Data are conflicting regarding
whether increased frequency of shocks is associated with the development of
psychiatric disorders, but patient concern about being shocked, regardless of
whether the shock occurs, appears to be correlated with psychological morbid-
ity (Pedersen et al. 2005). The literature regarding treatment is limited, but
findings are encouraging for the effectiveness of psychosocial interventions,
334 Clinical Manual of Psychosomatic Medicine

including preimplantation education programs and cognitive-behavioral ther-

apy (CBT), in reducing anxiety and improving quality of life (Lewin et al.
2009; Salmoirago-Blotcher and Ockene 2009; Sears et al. 2007).

Left Ventricular Assist Device

Left ventricular assist devices (LVADs) are used as an alternative therapy for
patients with end-stage heart failure who do not qualify for cardiac transplan-
tation or as a bridge for patients awaiting transplantation. LVADs as destina-
tion therapy were approved by the U.S. Food and Drug Administration in
2003. As the use of LVADs continues to rise, understanding the psychiatric
and quality of life issues involved for patients and transplant selection teams
has become increasingly important. The specific self-care behaviors required
for LVAD patients are different from those for transplant patients, but both
groups have many similarities, including the need to take multiple medica-
tions for a lifetime and to adhere to prescribed health behaviors, cardiac reha-
bilitation, frequent lab tests, and ongoing physician visits. The LVAD patient
also needs to perform technical tasks related to the device, which require the
cognitive ability to follow complex instructions. Patients receiving destination
therapy may initially feel hope and relief, but if they functionally decline, their
feelings may change to anger or disappointment that transplant is not an op-
tion (Eshelman et al. 2009).

Treatment Issues
Treatment of Depression and Reduction
of Cardiovascular Risk
Despite the link between CVD and depression, studies have not been able to
demonstrate a reduction in cardiovascular risk by treating depression (Thombs
et al. 2008).

• The Sertraline Antidepressant Heart Attack Randomized Trial (SADHART)

was the first trial to examine the safety and efficacy of sertraline treatment for
depressed patients hospitalized with acute MI or unstable angina. The study’s
major contribution was to demonstrate the safety of treatment with sertra-
line. Mortality was not significantly different between the treated and un-
 Cardiology 335

treated groups, and the efficacy data were mixed, with improvement
primarily found in the patients with severe or recurrent depression (Glass-
man et al. 2002).
• The Enhancing Recovery in Coronary Heart Disease (ENRICHD) study
found that CBT improved depression and social isolation in patients after
MI, but the effect size was small and CBT had no impact on cardiovascu-
lar morbidity or mortality (Berkman et al. 2003).
• The Canadian Cardiac Randomized Evaluation of Antidepressant and Psy-
chotherapy Efficacy (CREATE) trial demonstrated efficacy of citalopram
plus weekly clinical management for major depression among patients with
CVD, and found no benefit of interpersonal therapy over clinical manage-
ment (Lespérance et al. 2007).
• The Myocardial INfarction and Depression-Intervention Trial (MIND-
IT), an effectiveness trial to determine whether an active treatment strategy
resulted in better outcomes than usual care, demonstrated that antidepres-
sant treatment did not improve depression or cardiac prognosis (van Melle
et al. 2006, 2007), although mirtazapine appeared to be safe in patients af-
ter MI (Honig et al. 2007).

Pharmacological Considerations
The selective serotonin reuptake inhibitors (SSRIs) are generally considered
first-line treatments for patients with depression and CVD, in contrast to the
tricyclic antidepressants, which may delay cardiac conduction, increase heart
rate, and prolong the QT and PR intervals. Limited data suggest that SSRIs
may be cardioprotective, but further studies are needed (Evans et al. 2005;
Glassman et al. 2002). (See also Chapter 14, “Biological Treatments.”)

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ceived social support on clinical events after myocardial infarction: the Enhanc-
ing Recovery in Coronary Heart Disease Patients (ENRICHD) randomized trial.
JAMA 289:3106–3116, 2003
Blumenthal JA, Lett HS, Babyak MA, et al: Depression as a risk factor for mortality af-
ter coronary artery bypass surgery. Lancet 362:604–609, 2003
336 Clinical Manual of Psychosomatic Medicine

Bostwick JM, Sola CL: An updated review of implantable cardioverter/defibrillators,

induced anxiety, and quality of life. Psychiatr Clin North Am 30:677–688, 2007
Carney RM, Blumenthal JA, Stein PK, et al: Depression, heart rate variability, and
acute myocardial infarction. Circulation 104:2024–2028, 2001
Carney RM, Blumenthal JA, Catellier D, et al: Depression as a risk factor for mortality
after acute myocardial infarction. Am J Cardiol 92:1277–1281, 2003
Carney RM, Blumenthal JA, Freedland KE, et al: Low heart rate variability and the ef-
fect of depression on post-myocardial infarction mortality. Arch Intern Med
165:1486–1491, 2005
Eaker ED, Sullivan LM, Kelly Hayes M, et al: Tension and anxiety and the prediction
of the 10-year incidence of coronary heart disease, atrial fibrillation, and total
mortality: the Framingham Offspring Study. Psychosom Med 67:692–696, 2005
Eshelman AK, Mason S, Nemeh H, et al: LVAD destination therapy: applying what we
know about psychiatric evaluation and management from cardiac failure and
transplant. Heart Fail Rev 14:21–28, 2009
Evans DL, Charney DS, Lewis L, et al: Mood disorders in the medically ill: scientific
review and recommendations. Biol Psychiatry 58:175–189, 2005
Frasure-Smith N, Lespérance F: Depression and anxiety as predictors of 2-year cardiac
events in patients with stable coronary artery disease. Arch Gen Psychiatry 65:62–
71, 2008
Frasure-Smith N, Lespérance F: Depression and cardiac risk: present status and future
directions. Heart 96:173–176, 2010
Frasure-Smith N, Lespérance F, Talajic M: Depression following myocardial infarc-
tion: impact on 6-month survival. (Erratum in JAMA 271:1082, 1994.) JAMA
270:1819–1825, 1993
Frasure-Smith N, Lespérance F, Habra M, et al: Elevated depression symptoms predict
long-term cardiovascular mortality in patients with atrial fibrillation and heart
failure. Circulation 120:134–140, 2010
Gehi A, Mangano D, Pipkin S, et al: Depression and heart rate variability in patients
with stable coronary heart disease: findings from the Heart and Soul Study. Arch
Gen Psychiatry 62:661–666, 2005
Glassman AH, O’Connor CM, Califf RM, et al: Sertraline treatment of major depres-
sion in patients with acute MI or unstable angina. (Erratum in JAMA 288:1720,
2002.) JAMA 288:701–709, 2002
Ho PM, Masoudi FA, Spertus JA, et al: Depression predicts mortality following car-
diac valve surgery. Ann Thorac Surg 79:1255–1259, 2005
Honig A, Kuyper AMG, Schene AH, et al: Treatment of post-myocardial infarction
depressive disorder: a randomized, placebo-controlled trial with mirtazapine.
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 Cardiology 337

Horwitz RI, Viscoli CM, Berkman L, et al: Treatment adherence and risk of death after
a myocardial infarction. Lancet 336:542–545, 1990
Huffman JC, Pollack MH: Predicting panic disorder among patients with chest pain:
an analysis of the literature. Psychosomatics 44:222–236, 2003
Huffman JC, Smith FA, Blais MA, et al: Recognition and treatment of depression and anx-
iety in patients with acute myocardial infarction. Am J Cardiol 98:319–324, 2006
Joynt KE, Whellan DJ, O’Connor CM: Depression and cardiovascular disease: mech-
anisms of interaction. Biol Psychiatry 54:248–261, 2003
Kleiger RE, Miller JP, Bigger JT Jr, et al: Decreased heart rate variability and its asso-
ciation with increased mortality after acute myocardial infarction. Am J Cardiol
59:256–262, 1987
Kop WJ, Gottdiener JS, Tangen CM, et al: Inflammation and coagulation factors in
persons >65 years of age with symptoms of depression but without evidence of
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Kuhl EA, Fauerbach JA, Bush DE, et al: Relation of anxiety and adherence to risk-reduc-
ing recommendations following myocardial infarction. Am J Cardiol 103:1629–
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Lespérance F, Frasure-Smith N, Talajic M, et al: Five-year risk of cardiac mortality in
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jor depression. Am J Psychiatry 153:1313–1317, 1996
Pedersen SS, van Domburg RT, Theuns DA, et al: Concerns about the implantable
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plantable cardioverter defibrillators. Psychosomatics 46:451–457, 2005
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2003
 18
Dermatology

P sychiatric disorders are frequent among dermatology patients. The preva-

lence of DSM-IV-TR (American Psychiatric Association 2000) conditions in
these patients may be as high as 40% (Picardi et al. 2006). Several groups of
psychocutaneous conditions cut across DSM-IV-TR categories. Psychocuta-
neous conditions may be delusional (e.g., delusional parasitosis), somatoform
(e.g., body dysmorphic disorder), functional (e.g., unexplained pruritus), fac-
titious (e.g., dermatitis artefacta), or psychophysiological (e.g., atopic derma-
titis), or related to another psychiatric disorder (e.g., trichotillomania).

Delusional Psychocutaneous Conditions

Delusional psychocutaneous conditions share the characteristic that a fixed
false belief that defies reality testing is central to the clinical presentation. Psy-
chocutaneous disorders of delusional severity are among the most treatment-
resistant conditions encountered by psychosomatic medicine psychiatrists.
Evidence from randomized controlled treatment trials is lacking because many
people who believe or fear that they have a dermatological condition doubt or
reject the possibility that psychological factors may be relevant; therefore, they
are unlikely to participate in psychiatric treatment research. Limited knowl-
edge about effective management, coupled with the density of patients’ beliefs

339
340 Clinical Manual of Psychosomatic Medicine

about their skin symptoms, creates challenges in clinical management (Lep-

ping et al. 2007). Some psychosomatic medicine outpatient consultants report
anecdotal success in gaining access to patients by seeing them in the dermatol-
ogy clinic instead of in a psychosomatic medicine or general psychiatry clinic
(Rundell 2008; Woodruff et al. 1997).

Delusional Parasitosis
Clinical Presentation
Delusional parasitosis typically has a monosymptomatic presentation. Pa-
tients with delusional parasitosis seek dermatological care because they be-
lieve, despite compelling evidence to the contrary, that they have been invaded
by parasites. They vigorously assert their beliefs about what the organisms are
doing to their skin. Patients usually have a specific theory about how they
came to be infected; they see or sense skin lesions that others, including med-
ical professionals, cannot appreciate. Medical evaluations are normal.
Delusional parasitosis patients may generate high health care costs. Pa-
tients typically make multiple attempts at evaluation and treatment, often
moving from physician to physician and center to center in repeated attempts
to gain definitive evaluation and treatment. Each physician and clinic repeats
a comprehensive evaluation, often under substantial pressure from patients
and sometimes their families or friends.

Clinical Management
Pharmacological approaches. Advice regarding clinical management of de-
lusional parasitosis is based on small case series, case reports, and one very small
double-blind, placebo-controlled crossover study in 1982 (Hamann and Avn-
storp 1982; Lepping et al. 2007). In the controlled study, 10 of 11 patients who
received pimozide improved; this study was limited by small sample size and
lack of randomization. Antipsychotic medications said to be effective in case re-
ports or series include haloperidol, risperidone, quetiapine, trifluoperazine, flu-
phenazine, aripiprazole, olanzapine, and chlorpromazine (Lepping et al. 2007;
Sambhi and Lepping 2010). These case reports must be interpreted cautiously,
however, because unsuccessful treatments are not likely to be reported or ac-
cepted for publication. Use of antipsychotic medication requires attention to
the possibility of QTc prolongation and motor and metabolic adverse effects.
 Dermatology 341

Nonpharmacological approaches. Psychotherapy has minimal efficacy in

treatment of delusional parasitosis. Advice to dermatologists and general inter-
nists should include emphases on empathically listening to patients, conduct-
ing appropriate and regular examinations so patients will not feel compelled to
“doctor shop,” and focusing on each patient’s ability to function. The physi-
cians should make an effort not to reinforce the delusional beliefs; however,
they should also avoid taking a completely neutral stance that will make a pa-
tient guarded (Sandoz et al. 2008). Asking how the condition has affected the
patient’s life may lead to recommendations to the patient and family about im-
proving social or occupational functioning.

Other Delusional Disorders With Skin Manifestations

When anxiety or fear about a perceived skin-related condition becomes a fixed
false belief, the psychiatrist diagnoses delusional disorder, somatic type.

Clinical Presentations
Delusions apart from parasitosis can take the form of beliefs that ingested or
inhaled motile substances or shards may be forcing their way out through the
skin or beliefs about defects in appearance (akin to body dysmorphic disorder)
or skin odor (olfactory reference syndrome).

Clinical Management
Principles of treating delusions of motile substances or shards are the same as prin-
ciples of managing delusional parasitosis. Authors report anecdotal success with
managing delusional beliefs about defects in skin appearance with selective sero-
tonin reuptake inhibitors (SSRIs) (Phillips 1996; Phillips et al. 2002). If symp-
toms do not respond to SSRI medications, an antipsychotic may be helpful.

Somatoform Psychocutaneous Conditions

Body Dysmorphic Disorder
Clinical Presentation
Body dysmorphic disorder is a preoccupation with an imagined defect in ap-
pearance. Although the disorder may not be delusional in quality or severity,
it may be quite disabling and is surprisingly common in dermatology (Arnold
342 Clinical Manual of Psychosomatic Medicine

2005) and otorhinolaryngology clinics. (Body dysmorphic disorder is dis-

cussed in more detail in Chapter 12, “Somatoform and Related Disorders.”)

Clinical Management
Dermatological treatments and reassurance do not commonly result in im-
provements in body dysmorphic disorder. SSRI medications and cognitive-
behavioral therapy (CBT) can be helpful (Phillips et al. 2002).

Idiopathic (Unexplained) Pruritus

Clinical Presentation
Pruritus (itching) can occur with many medical conditions, allergies, and med-
ication adverse effects. When exhaustive investigation has not revealed a plau-
sible etiology (particularly if a patient has a history of psychological trauma, a
high stress level, or both), a shift toward psychiatric treatment can help prevent
a secondary dermatological problem from excessive scratching or self-admin-
istered topical agents.

Clinical Management
Case reports and case series suggest that tricyclic antidepressants, habit reversal
training, and CBT are often effective, at least in preventing complications of
scratching and in improving function (Rosenbaum and Ayllon 1981; Welko-
witz et al. 1989).

Factitious Psychocutaneous Conditions

Patients with psychocutaneous factitious disorder intentionally produce skin
lesions to assume an ongoing patient role. Arnold (2005) describes two main
categories of factitious disorders relevant to dermatology: factitious dermatitis
and psychogenic purpura. (See also Chapter 12, “Somatoform and Related
Disorders.”)

Factitious Dermatitis
In factitious dermatitis, also called dermatitis artefacta, patients assume the
sick role by intentionally producing skin lesions. Patients typically deny that
the lesions are self-inflicted (Arnold 2005; Sambhi and Lepping 2010).
 Dermatology 343

Clinical Presentation
Several methods of self-inflicted injury have been reported, including scratch-
ing, biting, picking, cutting, puncturing, or rubbing; applying heat, suction
cups, or caustic substances to the skin; and injecting foreign material such as
blood or feces (Gupta et al.1987; Koblenzer 1987). Lesions depend on meth-
ods used and may include excoriations, blisters, ulcers, erythema, edema, or
nodules (Koblenzer 1987).

Clinical Management
Anecdotal evidence suggests that patients may respond positively to efforts to pro-
tect the doctor-patient relationship. By maintaining a supportive relationship
with the patient over time, a primary care physician or dermatologist may increase
the chance that a patient will accept a psychotherapy referral (Koblenzer 1987).

Psychogenic Purpura
Spontaneous and unexplained appearance of recurrent purpura (bruising) is
considered most often to be a manifestation of factitious behavior (Arnold
2005). However, competing theories suggest that many cases may be the result
of conversion (no intentional behavior causing the bruising) or of autoeryth-
rocyte sensitization after trauma, such as an injury or surgery. Skin trauma
may result in future easy bruising because of sensitization to the stroma of ex-
travasated erythrocytes (Koblenzer 1987). When a patient presents with un-
explained bruising, consideration of nonfactitious explanations is important.

Psychiatric Disorders With

Dermatological Consequences
Trichotillomania
Chronic trichotillomania (pulling out of one’s hair) is classified in DSM-IV-
TR as an impulse-control disorder, but it frequently occurs in the context of
obsessive-compulsive disorder (OCD) (Stein et al. 1995a, 1995b). The im-
portance of compulsivity-related trichotillomania may be particularly relevant
in dermatology because the frequency of OCD in patients who consult der-
matologists may be four to five times higher than in the general population
(Ebrahimi et al. 2007).
344 Clinical Manual of Psychosomatic Medicine

Clinical Presentation
Patients with trichotillomania may impulsively or compulsively pull hair from
the scalp, eyelashes, eyebrows, pubic areas, and armpits. When the behaviors
are impulsive, the patient may feel dissociation or a detached state of mind dur-
ing the pulling behaviors (Gupta 2006). When the behaviors are compulsive or
occur in the context of OCD, the patient may experience anxiety relief. Pa-
tients with trichotillomania may have, in addition to OCD, concurrent mood
disorders, anxiety disorders, or personality disorders.

Clinical Management
Pharmacological approaches. Several controlled trials of antidepressant med-
ications have been conducted in patients with trichotillomania. Results are
mixed, but the most impressive results appear to have been achieved with clomip-
ramine, in terms of both outcome and study design (double-blind crossover)
(Swedo et al. 1989). Most SSRIs have been used to treat trichotillomania; in case
reports and case series, favorable results have been reported. Interpreting the large
number of positive cases reported is limited by publication bias, and controlled
trials of SSRIs are mixed in terms of outcome. In a few case reports, improved out-
comes in treatment-resistant cases were reported when low doses of antipsychotics
such as olanzapine or risperidone were added to SSRI medication (Arnold 2005).
Higher than usual dosages of antidepressant medications may also be helpful.
Nonpharmacological approaches. Controlled trials have demonstrated
that habit reversal training and CBT are efficacious for trichotillomania (Ni-
nan et al. 2000; van Minnen et al. 2003). Behavioral treatment may have bet-
ter results than medication for many patients (van Minnen et al. 2003). A
reasonable assumption is that the combination of pharmacotherapy and be-
havioral management may have better outcomes than medication alone for
trichotillomania, as has been demonstrated for other conditions.

Onychophagia
Onychophagia (nail biting) is common in childhood and adolescence. Like
trichotillomania, onychophagia may have both impulsive and compulsive
drivers (Arnold 2005). Evidence-based treatments include antidepressant
medication and habit reversal training (Twohig et al. 2003). Symptoms may
respond better to clomipramine than to other antidepressant medications.
 Dermatology 345

Dermatological Conditions Exacerbated

by Psychological Factors
Classified in DSM-IV-TR as examples of psychological factors affecting med-
ical conditions, a number of dermatological conditions can be sensitive to psy-
chological factors, as well as exacerbated by them.

Psoriasis
Clinical Presentation
Stress has been reported to trigger and exacerbate psoriasis (Arnold 2005).
Mechanisms of stress-induced exacerbations likely involve interactions be-
tween the nervous, immune, and endocrine systems. Up to 40% of psoriasis
patients may have mood or anxiety disorders, or clinically significant mood or
anxiety symptoms (Sharma et al. 2003). Some psychopharmacological medi-
cations, especially lithium, may cause or exacerbate psoriasis (Levenson 2008).

Clinical Management
Controlled studies have demonstrated that a number of behavioral interven-
tions—CBT, meditation, hypnosis, relaxation training, and stress manage-
ment training—result in reduced psoriasis activity (Fortune et al. 2002). No
controlled psychopharmacological trials for psoriasis treatment have been re-
ported, but the diagnosis and treatment of comorbid mood and anxiety dis-
orders are important.

Acne
Stress may aggravate acne, possibly through the increased release of adrenal
steroids, which affect sebaceous glands (Strauss and Thiboutot 1999). Acne,
in turn, causes increased anxiety and stress. Behavioral interventions, such as
biofeedback and relaxation training, may reduce acne severity, especially when
anxiety levels are high (Hughes et al. 1983).

Atopic Dermatitis
Atopic dermatitis is characterized by inflammation and itching that may
spontaneously appear and spontaneously resolve, and may recur in many epi-
sodes over a lifetime. Atopic dermatitis often has its onset in childhood.
346 Clinical Manual of Psychosomatic Medicine

Clinical Presentation
Allergies, contact irritants, airborne irritants, sweating, hormones, and stress
have all been linked to triggering or exacerbating episodes of dermatitis (Morren
et al. 1994). Flare-ups may be influenced by proinflammatory cytokines, which
in turn are modulated by psychosocial stressors (Davis 2007). Controlled stud-
ies have found that as a group, patients with adult atopic dermatitis are more
anxious and depressed than are disease-free controls and comparison groups
with other medical conditions (Ehlers et al. 1995; Schmitt et al. 2009).

Clinical Management
Addressing distress, anxiety, and depression may improve health-related quality
of life for patients with atopic dermatitis (Kiebert et al. 2002). Pharmacological
strategies center on treating comorbid mood or anxiety disorders and attempt-
ing to treat dermatological, anxiety, and distress symptoms with antidepres-
sants that have histamine receptor antagonism (e.g., doxepin, trimipramine)
(Savin et al. 1979). Controlled trials have demonstrated effectiveness of habit
reversal training, relaxation training, CBT, and stress management training as
adjuncts to standard medical care for atopic dermatitis when a patient has as-
sociated depression and anxiety (Ehlers et al. 1995).

References
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disor-
ders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Associ-
ation, 2000
Arnold LM: Dermatology, in The American Psychiatric Publishing Textbook of Psy-
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 19
Disaster and
Terrorism Casualties

F ollowing a disaster or terrorist attack, individuals with surgical injuries or

medical conditions have an increased likelihood of having a psychiatric con-
dition. Many times more patients go to medical facilities because of fear of
exposure to toxic agents than because of actual toxic exposure (Rundell 2003,
2005). The following list includes useful information for consultation psychi-
atrists working with disaster and terrorism casualties.

• Psychiatric symptoms. Psychiatric symptoms in victims of disasters should

be evaluated within the context of concurrent medical-surgical assessment
and treatment (Rundell 2005).
• Health systems. Careful differential diagnosis and timely communication
to the public lessen the risk of misdiagnosis and mass hysterical reactions,
thereby protecting health care systems from being overwhelmed (Rundell
and Christopher 2004).
• Patient categories. Following a potential mass toxic exposure, three types of
patients present themselves for medical evaluation:

349
350 Clinical Manual of Psychosomatic Medicine

1. People with disease due to the toxic agent

2. People who have disease due to the toxic agent in addition to a con-
current psychiatric condition
3. People who have not been exposed but fear they have

Unique Considerations in Clinical Evaluation

Symptom Overlap

• Anxiety provoked by having been potentially exposed to a substance or

disease can complicate diagnosis.
• Physiological signs of autonomic nervous system arousal and dysphoria can
mimic symptoms and signs of toxic exposure or other medical diseases.
• Signs and symptoms, and effects of treatment, of chemical and biological
attacks can be nonspecific and mimic neuropsychiatric syndromes.
• Differential diagnosis by skilled clinicians is crucial to effective triage of
large populations.
• Presence or absence of fever may, in many cases, be the only reliable early
differentiator between those exposed to a biological agent and those not
exposed but fearful they may have been.

Triage Concepts
Advanced Trauma Life Support
The underlying concept of Advanced Trauma Life Support (ATLS) is simple:
the greatest threats to life—loss of airway, loss of breathing ability, loss of cir-
culating blood volume, and effects of an expanding intracerebral mass—are
treated first (American College of Surgeons 2004). This standardized approach
to handling trauma patients involves two surveys:

• The primary survey is a rapid, targeted examination necessary to identify

life-threatening injuries to the airway and blood circulation. The purpose
is to assess whether the patient is alert, responsive to verbal stimuli, re-
sponsive to painful stimuli, or unresponsive.
 Disaster and Terrorism Casualties 351

• The secondary survey is a head-to-toe evaluation of the trauma patient in

which each region of the body is systematically examined and all available
medical history (allergies, current medications, significant past illnesses,
and events related to the injury or exposure) is reviewed.

Early Identification of Psychiatric Casualties

The postdisaster or postterrorism psychiatric screening examination that is
used for triage and identification of early psychiatric casualties can be thought
of as a tertiary survey that focuses on the most common psychiatric sequelae
(Rundell 2003) and those most likely to adversely affect outcomes.

• The screening psychiatric examination of the traumatized victim is easier

if findings from the primary and secondary ATLS surveys are unremark-
able. Psychiatric symptoms are then likely to represent primary psychiatric
disorders.
• When psychiatric signs are present in addition to significant primary and
secondary survey findings, differential diagnosis can be complex, and the
patient may have multiple disorders.

Key principles of psychiatric screening of disaster victims following primary

and secondary surveys and medical stabilization are summarized in Table 19–1.

Unique Considerations in Diagnosis

and Management
Delirium
Diagnosis
• In the disaster or terrorism victim with major illness or injuries, volume
depletion and metabolic derangements can cause delirium: clouded con-
sciousness, agitation or diminished responsiveness, and disorientation.
• Common causes of delirium in disaster settings include hypovolemia, hy-
poxemia, central nervous system mass effect, infection, and adverse effects
of ATLS and Advanced Cardiovascular Life Support (ACLS) medications.
352 Clinical Manual of Psychosomatic Medicine

Table 19–1. Screening psychiatric examination of medical-

surgical disaster casualties
Examination parameter Finding increases likelihood of:

History

Sustained physical injuries during Secondary psychiatric disorder,a ASD,

traumatic event PTSD, dissociation
Past history of psychiatric disorder That psychiatric disorder
Patient is on routine, ongoing Substance intoxication, substance
medication withdrawal, secondary psychiatric
disorder
Received ATLS or ACLS medications Secondary psychiatric disordera

Physical findings

Elevated heart rate, blood pressure Substance withdrawal, generalized anxiety

disorder, panic disorder, ASD, PTSD,
secondary psychiatric disordera
Easy startle ASD, PTSD, generalized anxiety disorder
Lateralizing neurological signs Head or vertebral column injury,
secondary psychiatric disordera
Physical complaints out of proportion Conversion disorder, hypochondriasis,
to objective findings factitious disorder, malingering,b
undiagnosed physical condition

Mental status examination

Disoriented Delirium, secondary psychiatric disordera

Clouded consciousness Delirium, secondary psychiatric disorder,a
dissociation
Dysarthria Substance intoxication, head injury
Dysgraphia, dyscalculia Head injury, delirium
Impaired short-term memory Head injury, substance intoxication,
delirium, generalized anxiety disorder,
panic attack
 Disaster and Terrorism Casualties 353

Table 19–1. Screening psychiatric examination of medical-

surgical disaster casualties (continued)
Examination parameter Finding increases likelihood of:

Hallucinations or delusions Substance intoxication, secondary

psychiatric disorder,a substance
withdrawal, primary psychotic disorder

Note. ACLS = Advanced Cardiovascular Life Support; ASD = acute stress disorder; ATLS = Ad-
vanced Trauma Life Support; PTSD=posttraumatic stress disorder.
aPsychiatric disorders due to general medical conditions or due to toxins/psychoactive substances.
b
Malingering is not a psychiatric disorder; it is a legal accusation.
Source. Adapted from Rundell JR: “Assessment and Management of Medical-Surgical Disaster
Casualties,” in Textbook of Disaster Psychiatry. Edited by Ursano RJ, Fullerton CS, Weisaeth L, et
al. New York, Cambridge University Press, 2005, pp. 164–189. Used with permission.

Management
• Prevention of or resolution of the delirium etiology should be the main
goal and requires resolving the metabolic sequelae of the injury.
• Although medication treatment of delirium symptoms can help decrease
psychosis and agitation, as well as mitigate a safety problem, this is not the
ideal management.
– Medications used to manage agitation can further complicate both
medical assessment and an already difficult clinical course.
– Symptomatic management of the patient’s behavioral problems with
sedating medication should be initially reserved to protect the life or
safety of the patient and other patients or staff.

Depression
Diagnosis
• Depressed mood or resignation in the aftermath of a disaster or terrorist
event may be difficult to distinguish from the malaise and lassitude com-
mon among the prodromes of many chemical and bioterrorism exposures.
• Differential diagnosis is based on assessment of the patient’s predisposi-
tion, timeline of syndrome development, and presence or absence of bio-
logical factors that could produce mood symptoms.
354 Clinical Manual of Psychosomatic Medicine

Management
Antidepressant medications and cognitive-behavioral psychotherapy are the
mainstays of treatment for major depressive disorder following disaster or
trauma, and may assist with managing subsyndromal depression.

Acute Stress Disorder and Posttraumatic Stress Disorder

Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) can be
substantial burdens following a major terrorist event. Among 1,008 adults in-
terviewed in New York City between 1 and 2 months after the attacks on the
World Trade Center, 7.5% reported symptoms consistent with a diagnosis of
current PTSD (Galea et al. 2002).

Diagnosis
• ASD and PTSD are frequently comorbid with major depressive disorder,
panic disorder, substance use disorder, and generalized anxiety disorder
(Rundell 2005).
• Having a physical injury increases the risk of ASD and PTSD (Rundell
2005).
– Mild traumatic brain injury is associated with increased frequency of
PTSD.
– Returning Iraq war veterans who reported injuries with loss of con-
sciousness are three times more likely than soldiers who reported no
injuries (27% vs. 9%) to report PTSD symptoms (Hoge et al. 2008).

Management
Medication treatment.
• Selective serotonin reuptake inhibitors (SSRIs) are the first-line medica-
tion treatment for the PTSD symptoms of reexperiencing, insomnia, and
arousal. Five SSRIs have demonstrated efficacy in at least one double-
blind, placebo-controlled trial, although up to 50% of patients may be
treatment resistant (Lineberry et al. 2006; see Table 19–2).
• Prazosin (mean dosage 9 mg/day at bedtime) was superior to placebo for
managing distressing dreams, insomnia, and functional status in a 20-week
double blind, placebo-controlled, crossover study of patients with PTSD
(Raskind et al. 2003).
 Disaster and Terrorism Casualties 355

Table 19–2. Studies demonstrating efficacy of selective serotonin

reuptake inhibitors (SSRIs) in posttraumatic stress disorder
SSRI Number of studies Mean dosage

Sertraline 2 133–146 mg/day

Paroxetine 2 20–50 mg/day
Fluoxetine 1 57 mg/day
Fluvoxamine 1 150 mg/day
Citalopram 1 30 mg/day
Source. Lineberry et al. 2006.

• Anecdotal reports suggest that low doses of antipsychotics (e.g., quetia-

pine 25 mg at bedtime) may help with insomnia and arousal (Lineberry et
al. 2006).

Psychotherapy
The two psychotherapies most frequently discussed as helpful for PTSD are
cognitive-behavioral therapy and marital therapy (Lineberry et al. 2006).

Health Anxiety and Hypochondriasis

In the generally anxious atmosphere and uncertainty following disasters and
terrorist events, patients who are prone to health anxiety or hypochondriasis
may have problems managing their anxiety and beliefs.
Diagnosis

• Six months of symptoms are required before making a diagnosis of hypo-

chondriasis.
• The patient with hypochondriasis has bodily preoccupation and vigilance
regarding body sensations.

Management
Health anxiety and subsyndromal hypochondriacal fears may be widespread
among the general population following a disaster or terrorist event, and
should be managed with reassurance and a degree of tolerance for patients’ re-
quests for appointments and examinations by their primary care providers.
356 Clinical Manual of Psychosomatic Medicine

Unexplained Physical Symptoms and

Conversion Symptoms
Not all unexplained physical symptoms are conversion symptoms, although
conversion is well documented anecdotally after terrorist and combat events.
Even though little scientific basis exists for future prevention and care of un-
explained physical symptoms (Clauw et al. 2003), persons with unexplained
symptoms need to be identified in the triage process so that inappropriate and
potentially harmful treatments are not conducted and to avoid drawing re-
sources away from victims needing them.

Dissociation and Dissociative Disorder

Dissociation is a disruption in the usually integrated functions of conscious-
ness, memory, identity, or perception of the environment.

• The core feature of dissociative disorder is the presence of significant dis-

tress or of significant disruption in social or occupational functioning.
• Dissociation that falls short of diagnostic criteria for dissociative disorder
is common in the context of any traumatic or terrorist event.
• Dissociation is generally underrecognized in the immediate aftermath of a
traumatic event or terrorist event (Rundell 2005).
• Dissociation may be adaptive in the immediate aftermath of a trauma, because
it may prevent the eruption of intolerable affects or the unleashing of poten-
tially dangerous impulses or behaviors (e.g., attempts to flee the scene).
• Identifying otherwise uninjured disaster victims who are simply dissociat-
ing frees up scarce evaluation and treatment resources for other emergency
patients.
• Dissociation and diminished neurological responsiveness are easily con-
fused. A key role for a consulting psychiatrist in the immediate aftermath
of a disaster, while primary and secondary surveys are being done, is to
help identify dissociation. The following are helpful in this identification:
– Gently tap patients on the shoulder and ask if they need anything and
whether they know where they are and what day it is.
– Watch for a muted but appropriate response in a dissociating person;
this response indicates that level of consciousness and orientation is
grossly intact.
 Disaster and Terrorism Casualties 357

Substance Use Disorders

Following a disaster or terrorism event, people may increase their use of alco-
hol or drugs as a way to decrease the acute despair or anxiety associated with
the event.

• Rescue and health care workers are at risk because of their participation in
and exposure to the aftermath of the event.
• Disaster response leaders must educate and model for their workers the
avoidance of alcohol and drugs during the disaster management period
and its aftermath.
• Patients who have substance-related disorders may present intoxicated or in
withdrawal at a triage or patient management area. Health care workers can
confuse effects of either intoxication or withdrawal with toxicities associated
with chemical agents, biological agents, metabolic derangements, or medi-
cations used to treat patients’ medical-surgical conditions. Patients may also
present seeking prescription medications with the potential for abuse.

Effects of Disaster Medications

An important part of postdisaster psychiatric screening is to find out what
medications an injured patient has received, in what amounts, and over what
time period. Disaster and resuscitation agents such as intravenous fluids (wa-
ter), epinephrine, lidocaine, atropine, sedatives, nitroglycerin, and morphine
are commonly used and have significant psychiatric or autonomic effects.

• Atropine causes significant anxiety and anticholinergic effects.

• Epinephrine causes blood pressure and heart rate elevations, and causes
patients to feel anxious or panicky.
• Morphine causes sedation and impairs orientation and responsiveness.

References
American College of Surgeons: Advanced Trauma Life Support for Doctors—Student
Course Manual, 7th Edition. Chicago, American College of Surgeons, 2004
Clauw DJ, Engel CC, Aronowitz R, et al: Unexplained symptoms after terrorism and
war: an expert consensus statement. J Occup Environ Med 45:1040–1048, 2003
358 Clinical Manual of Psychosomatic Medicine

Galea S, Ahern J, Resnick H, et al: Psychological sequelae of the September 11 terrorist

attacks in New York City. N Engl J Med 346:982–987, 2002
Hoge CW, McGurk D, Thomas JL, et al: Mild traumatic brain injury in U.S. soldiers
returning from Iraq. N Engl J Med 358:453–463, 2008
Lineberry TW, Ramaswamy S, Bostwick M, et al: Traumatized troops: how to treat
combat-related PTSD. Curr Psychiatr 5:53–56, 2006
Raskind MA, Peskind ER, Kanter ED, et al: Reduction of nightmares and other PTSD
symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psy-
chiatry 160:371–373, 2003
Rundell JR: A consultation-liaison psychiatry approach to disaster/terrorism victim as-
sessment and management, in Terrorism and Disaster: Individual and Commu-
nity Mental Health Interventions. Edited by Ursano RJ, Fullerton CS, Norwood
AE. New York, Cambridge University Press, 2003, pp. 107–120
Rundell JR: Assessment and management of medical-surgical disaster casualties, in
Textbook of Disaster Psychiatry. Edited by Ursano RJ, Fullerton CS, Weisaeth L,
et al. New York, Cambridge University Press, 2005, pp 164–189
Rundell JR, Christopher GW: Differentiating manifestations of infection from psy-
chiatric disorders and fears of having been exposed to bioterrorism, in Bioterror-
ism. Edited by Ursano RJ and Norwood AE. New York, Cambridge University
Press, 2004, pp 88–108
 20
Endocrinology

E ndocrinopathies arise from and involve a broad array of organs and have
far-reaching pathophysiological disruption, both central and peripheral. Ini-
tial symptoms may be cryptic and covert or definitive and dramatic. The di-
verse biochemical sequelae of endocrine disturbances help explain both the
frequency and variety of neuropsychiatric consequences, some of which pre-
cede discernible somatic disease and may confound even the astute clinician.
Only the most prevalent examples are discussed in this chapter.

Diabetes Mellitus
Nearly 10% of adults in the United States have diabetes mellitus, including
20% of those over age 65. The annual incidence of new cases is approaching
1 million; 90%–95% of existing and new cases are type 2. Poorly controlled
diabetes mellitus, whether type 1 or type 2, disposes the patient to macrovas-
cular and microvascular sequelae, including retinopathy, cardiovascular dis-
ease, nephropathy, nontraumatic limb amputation, and peripheral neuropa-
thy. In the United Kingdom, a large prospective study found that a 1-point

359
360 Clinical Manual of Psychosomatic Medicine

shift in hemoglobin A1c (HbA1c) was associated with a 35% shift in develop-
ment of complications (Goebel-Fabbri et al. 2011). Comorbid depression and
diabetes mellitus compound the morbidity and expense associated with each,
emphasizing the importance of clinical awareness and intervention.

Depression and Diabetes

The association between diabetes and depression is bidirectional. Depression,
independent of multiple confounding factors, is associated with a 60%–65%
increased risk for development of type 2 diabetes; however, antidepressant
treatment is not associated with an increased risk of diabetes (Campayo et al.
2010; Mezuk et al. 2008; Musselman et al. 2003). A recent review of largely
prospective epidemiological studies suggests that anxiety, anger, hostility,
sleeping problems, and general emotional distress are also associated with an
increased risk for development of type 2 diabetes (Pouwer et al. 2010).

Pathophysiology
Possible pathophysiological mechanisms for the association between diabetes
and depression include the following:

• Counterregulatory hormones (catecholamines, glucocorticoids, growth

hormone, and glucagon) are released in response to stress and in depres-
sion; these hormones oppose the glucoregulatory effect of insulin.
• Alterations in glucose transport and utilization occur.
• Proinflammatory cytokines, which are increased in depression, induce
“sickness behavior.” One of these cytokines, tumor necrosis factor–alpha, is
overproduced in the adipose and muscle tissue of obese individuals, poten-
tially increasing fatigue and leading to decreased physical activity (Golden
2007; Musselman et al. 2003).

Behavioral Consequences
The following behavioral consequences of depression may predispose to dia-
betes and/or further impede diabetic control (Katon 2008; Katon et al. 2009;
Musselman et al. 2003):

• Physical inactivity and obesity

• Nonadherence to dietary guidelines
 Endocrinology 361

• Inconsistent blood glucose monitoring

• Poor compliance with medication

Diabetes and Depression

The prevalence of depression in persons with diabetes is two to three times
higher than in the general population, although the absolute risk of depression
following type 2 diabetes is only 15% (Mezuk et al. 2008). Patients with more
extensive complications of diabetes, less education, socioeconomic hardship,
and chronic stressors are at higher risk for developing depression (Musselman
et al. 2003). The mechanism whereby diabetes may predispose to depression
is unclear. Indirect suggestions include the following:

• Dysglycemia and malaise. Glycemic control is associated with increased

subjective well-being (Lustman and Clouse 2005).
• Cognitive contribution. Hyperglycemia is associated with cognitive impair-
ment (Cukierman-Yaffe et al. 2009; Solanki et al. 2009).
• Treatment effect. Untreated type 2 diabetes is not associated with an in-
creased risk of depression; the increased association occurs only in patients
with treated type 2 diabetes (Golden et al. 2008).

Consequences of Comorbid Depression and Diabetes

The consequences of comorbid depression and diabetes are multiple and sub-
stantial:

• The course of depression is intensified, with up to 80% of patients expe-

riencing a depressive relapse within 5 years (Katon 2008).
• Diabetic patients respond less robustly to antidepressants than matched
control subjects without diabetes (Bryan et al. 2010).
• Depression is associated with poorer medical outcomes and increased dia-
betic complications (Lustman et al. 2007).
• Depression is associated with a threefold to fivefold increased risk of mor-
tality in patients with diabetes (Black et al. 2003; Ismail et al. 2007).
• Health care costs are markedly increased. A recent study demonstrated
that the annual Medicare patient cost for patients with comorbid diabetes
and depression was 4.5 times greater than for nondepressed patients with
diabetes (Katon 2008).
362 Clinical Manual of Psychosomatic Medicine

Treatment
Treatment is imperative to reduce suffering and conserve resources. Pharma-
cological treatment, cognitive-behavioral therapy, or both have been studied
in patients with comorbid depression and diabetes.

Pharmacological Treatment

• Tricyclic antidepressants are effective for depression and neuropathic pain

(Saarto and Wiffen 2010) but are associated with weight gain and cardiac
effects.
• Selective serotonin reuptake inhibitors (SSRIs) are tolerated well by dia-
betic patients, with fewer side effects than among nondiabetic control pa-
tients (Bryan et al. 2010). With the possible exception of paroxetine, SSRIs
are effective for treatment of depression in patients with diabetes but do not
improve medical outcome (Petrak and Herpetz 2009).
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) are more likely to
reduce neuropathic pain than SSRIs; duloxetine, milnacipran, and ven-
lafaxine have had favorable results in this population (Abrahamian et al.
2009; Lee and Chen 2010; Sultan et al. 2008).
• Mirtazapine may also reduce neuropathic pain but is generally avoided be-
cause it is associated with more weight gain than other newer antidepres-
sants.
• Bupropion is not associated with weight gain and is the least likely to con-
tribute to sexual dysfunction; one study has shown improvement in
mood, body mass index, and HbA1c (Toplak and Abrahamian 2009).

Cognitive-Behavioral Therapy
Cognitive-behavioral therapy is effective in the treatment of depression (Pe-
trak and Herpetz 2009) and in one study demonstrated a significant decrease
in HbA1c levels at 6-month follow-up (Lustman et al. 1998).

Combined Psychotherapy and Pharmacotherapy

Combined psychotherapy and pharmacotherapy may be prudent for diabetic
patients with severe or refractory depression who are unresponsive to trials of
either modality alone. Although combined therapy yields greater efficacy, a re-
flexive recommendation for combined therapy for all depressed patients over-
 Endocrinology 363

looks individual preferences, probability of adherence, and cost issues.

Integrated treatment with interpersonal therapy and citalopram is the only
strategy studied to date that has demonstrated a significant decrease in 5-year
mortality (Bogner et al. 2007).

Thyroid Disease
Hypothalamic thyrotropin-releasing hormone (TRH) stimulates pituitary
production of thyrotropin, which regulates thyroid secretion of thyroxine
(T4), triiodothyronine (T3), and reverse T3 (rT3). Ninety-nine percent of
these thyroid hormones are protein bound; only unbound hormones are ac-
tive. The thyroid gland is the sole source of T4 and about 20% of T3, the re-
mainder of which is derived throughout the body by deiodinase enzymes,
which strip iodine from T4. In the brain, the neuron is the principal site of T3
action. Although thyroid hormone receptors occur throughout the central
nervous system (CNS), the amygdala, cortex, and hippocampus are richly
supplied, consistent with their integral roles in mood regulation and cognitive
function (Bauer et al. 2008; Williams 2008).

Hypothyroidism
Hypothyroidism is associated with neurological and psychiatric disruption
(Lass et al. 2008).

Cognitive Dysfunction
Cognitive dysfunction, most commonly in the domains of working memory
and executive function, is associated with both hypothyroidism and hyperthy-
roidism. Individuals with grossly normal thyroid function but elevated free T4
concentrations demonstrated deterioration in Mini-Mental State Examination
scores 2 years later, prompting the proposal that perhaps elevated T4 leads to
oxidative stress and secondary neuronal damage (Hogervorst et al. 2008).

Depression
More often than not, low thyrotropin and low T3 are associated with depres-
sion. However, studies of thyroid function and depression are less uniform
than conventional wisdom would suggest. T4 levels in the high-normal range
have also been linked to depression. Thyroid disorders were the only medical
364 Clinical Manual of Psychosomatic Medicine

comorbidity among rapid cyclers in a sample of 1,090 patients with bipolar I

disorder; unfortunately, patient history rather than laboratory confirmation
was used to establish thyroid dysfunction (Bunevicius 2009). A tentative con-
clusion drawn from divergent observations in different studies is that patients
with thyroid disorders who develop depression and patients with depression
who develop thyroid dysfunction may have different biochemical profiles.
Patients with comorbid depression and thyroid dysfunction may benefit
from treatment with antidepressants and/or thyroid augmentation:

• Antidepressants of multiple classes have shown efficacy in patients with

comorbid depression and thyroid dysfunction, although different agents
appear to promote different thyroid hormone effects (Bunevicius 2009).
• T4 and/or T3 augmentation of conventional antidepressants in euthyroid
but depressed patients is a time-honored strategy, but studies and at-
tempted meta-analyses have drawn discordant conclusions regarding the
degree of efficacy; T3 is generally regarded as superior to T4.

Delirium
Hashimoto’s encephalopathy is a pleomorphic autoimmune syndrome that may
include multiple neuropsychiatric signs and symptoms: aphasia, ataxia, cogni-
tive compromise ranging from confusion to coma, headache, mood distur-
bance, paranoia, personality change, seizures, sleep disturbances, strokelike epi-
sodes, and visual hallucinations. The clinical course may be acute, subacute,
chronic, or relapsing-remitting (Mijajlovic et al. 2010; Schiess and Pardo 2008).
Thyroid function is almost always normal, biochemically and clinically. The
pathogenesis remains unclear, but elevated titers of antithyroid peroxidase anti-
bodies are present in more than 95% of cases, and antithyroglobulin antibodies
in more than 70%. The differential diagnosis includes Creutzfeldt-Jakob dis-
ease, CNS lupus, paraneoplastic and nonparaneoplastic limbic encephalitis,
rapidly progressive dementias, and vasculitis (Mocellin et al. 2007).
Patients with Hashimoto’s encephalopathy often benefit from pharmaco-
therapy.

• High-dose corticosteroids are commonly very effective in treating Hashi-

moto’s encephalopathy, emphasizing the importance of clinician diagnostic
vigilance despite the cryptic and often severe presentation of these patients.
 Endocrinology 365

• Other immunomodulators, such as cyclophosphamide, immunoglobulin,

and methotrexate, as well as plasmapheresis, have been effective when cor-
ticosteroids were not (Mocellin et al. 2007).

Hyperthyroidism
Hyperthyroidism is most commonly the result of Graves disease, an autoim-
mune disorder caused by thyroid-stimulating immunoglobulins that bind to
thyroid-stimulating hormone receptors and thereby precipitate production of
T4 and T3. Uncommonly, a patient may ingest excessive thyroid hormone in
hope of boosting energy or enabling weight loss.
Neuropsychiatric consequences of hyperthyroidism include anxiety, apa-
thy, cognitive inefficiency, dysphoria, fatigue, irritability, mood disturbances
ranging from depression to mania, memory difficulties, and tremulousness.
Elderly patients with hyperthyroidism more commonly experience apathy
and depression, whereas younger adult patients are more likely to be kineti-
cally restless and anxiously dysphoric (Goebel-Fabbri et al. 2011).
Restoring normal thyroid function, whether by thyroidectomy, antithy-
roid medication, or radioactive iodine, is essential to reversing the psychiatric
sequelae of thyrotoxicosis.

Parathyroid Disorders
Parathyroid disorders may precipitate a range of psychiatric symptoms, pri-
marily generated by elevated or depleted serum calcium.

Hyperparathyroidism
Hyperparathyroidism is the oversecretion of parathyroid hormone. The con-
sequent hypercalcemia can cause anergia, anxiety, apathy, dysphoria, and im-
paired concentration and memory; severe hypercalcemia is associated with a
full spectrum of psychotic symptoms. Restoration of normal calcium levels
brings about resolution of psychiatric and cognitive symptoms for most pa-
tients (Roman and Sosa 2007).

Hypoparathyroidism
Hypoparathyroidism, the result of inadequate parathyroid hormone secretion
typically caused by prior surgery, presents with hypocalcemia-mediated pares-
366 Clinical Manual of Psychosomatic Medicine

thesias and muscle cramping. Anxiety and irritability often accompany neuro-
muscular symptoms; if unrecognized and untreated, cognitive difficulties may
follow (Goebel-Fabbri et al. 2011).

Adrenal Gland Disorders

Adrenal gland disorders may cause a broad range of psychiatric symptoms.

Cushing’s Syndrome
Cushing’s syndrome, whether the result of excess corticotropin triggered by a
pituitary or adrenal tumor or the result of administered corticosteroids, occurs
due to supranormal levels of cortisol. Although depressive symptoms occur in
more than 50% of patients with Cushing’s syndrome, patients may also be re-
ferred to the psychiatric consultation service because of anxiety, cognitive im-
pairment, hypomania, mania, and psychosis (Arnaldi et al. 2003; Brown 2009).

Adrenal Insufficiency
Adrenal insufficiency occurs for many reasons, including Addison’s disease
(i.e., primary adrenal insufficiency) and chronic glucocorticoid administra-
tion. Addisonian crisis may precipitate delirium and psychosis. Patients with
gradual development of inadequate adrenal corticosteroid production experi-
ence anhedonia, anorexia, apathy, fatigue, and social withdrawal (Goebel-
Fabbri et al. 2011).

Osteoporosis
Osteoporosis, as well as the consequent increased risk of fractures, is linked to
psychiatric illness and treatments in multiple areas.

Depression
Depression is a significant risk factor for osteoporosis (Bab and Yirmiya 2010;
Cizza et al. 2009; Williams et al. 2009).

Selective Serotonin Reuptake Inhibitors

SSRIs are likely an independent risk factor for osteoporosis, although con-
founding factors make this research challenging (Haney et al. 2010).
 Endocrinology 367

Antipsychotic-Induced Hyperprolactinemia
Antipsychotic-induced hyperprolactinemia, which is a greater risk in patients tak-
ing first-generation antipsychotics, as well as risperidone and paliperidone, results
in decreased bone mineral density (Bostwick et al. 2009; Byerly et al. 2007).

Pheochromocytoma
Pheochromocytomas are very rare tumors, and approximately 10% prove ma-
lignant. These tumors secrete excessive catecholamines, resulting in multiple
and sometimes paroxysmal hyperadrenergic signs and symptoms. Although
pheochromocytoma invariably appears in the textbook differential diagnosis
of panic disorder and severe anxiety, laboratory testing for pheochromocy-
toma is not recommended when the patient presents only with psychiatric
symptoms, but should be considered when unresponsive hypertension or per-
sistent headaches are present (Goebel-Fabbri et al. 2011).

Vitamins
Vitamins are essential organic compounds that cannot be produced in suffi-
cient quantities by the body to serve the diverse biochemical tasks necessary,
and therefore require dietary or other supply. Vitamins function as antioxi-
dants, coenzymes, immunomodulators, precursors for enzyme cofactors, and
hormonelike regulators of metabolism and cell differentiation. Although his-
torically well-known sequelae of many vitamin deficiencies are now rare in the
developed world, some deficiencies still affect patients whom the psychoso-
matic medicine physician will encounter.
Vitamin B1
Vitamin B1 (thiamine) may be deficient in patients with alcohol dependence,
starvation (e.g., severe anorexia), short gut syndrome, lymphoma (particularly
following chemotherapy), and chronic hemodialysis, as well as patients who
have had gastric bypass surgery. Administering intravenous glucose to a thia-
mine-deficient patient may precipitate overt Wernicke’s encephalopathy.
Vitamin B3
Vitamin B3 (niacin) deficiency results in pellagra, classically characterized by
diarrhea, dermatitis, and dementia.
368 Clinical Manual of Psychosomatic Medicine

Vitamin B6
Vitamin B6 (pyridoxine) deficiency impairs proprioception; supplementation
may ameliorate some peripheral neuropathies.

Vitamin B9
Vitamin B9 (folic acid) is commonly tested in tandem with vitamin B12 be-
cause an excess of the former may mask the symptoms of vitamin B 12 defi-
ciency; however, vitamin B9 is rarely found to be deficient except in alcohol-
dependent patients.

Vitamin B12
Vitamin B12 (cyanocobalamin) deficiency causes megaloblastic anemia and a
range of neuropsychiatric disorders, including anxiety, delirium, dementia,
and mood disturbances.

Vitamin D
Vitamin D (cholecalciferol) has earned renewed interest because recent scru-
tiny has revealed multiple potential consequences of hypovitaminosis D, rang-
ing from depression to autoimmune and inflammatory conditions, as well as
pain and oncological susceptibility (de Abreu et al. 2009).

Vitamin E
Vitamin E (tocopherol) has had fluctuating popularity as a dietary supple-
ment intended to stave off progression of mild cognitive impairment or to re-
duce the risk of Alzheimer’s disease. Although studies continue, at present no
compelling evidence has been reported to mandate its use for these purposes.

Other Factors
Careful endocrine assessment is warranted when patients have any of the fol-
lowing (Kornstein et al. 2000):

• Comorbid mood disturbance, unusual behavioral symptoms, and cogni-

tive dysfunction
• Atypical and/or fluctuating psychiatric presentations
 Endocrinology 369

• Psychiatric symptoms that are refractory to standard treatment strategies

• Cognitive deterioration and/or dementia
• Affective symptoms following a closed head injury
• Personal or family history of antecedent endocrine or psychiatric dysfunc-
tion

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 21
Fatigue and Fibromyalgia

Fatigue
Fatigue is a complex problem with a wide range of conditions and symptoms
that may cause or co-occur with it. Assessment requires consideration of both
medical and psychological factors. Fatigue is a common medical complaint:
one-fourth of patients in primary care settings describe it as a major problem
(Kroenke et al. 1988).

Definition
Fatigue is the inability to initiate activity due to the perception of generalized
weakness and/or lessened capacity or motivation to maintain activity (Evans
and Lambert 2007). It should be distinguished from somnolence or muscle
weakness even though these symptoms may occur with fatigue. Fatigue is con-
sidered chronic when symptoms persist for at least 6 months.

Epidemiology and Etiology of Fatigue

Prevalence
The prevalence of fatigue in the general population is 7%, and the lifetime
rate is 25% (Walker et al. 1993). Fatigue is generally more common in women

373
374 Clinical Manual of Psychosomatic Medicine

than men (Kroenke et al. 1988). Medically unexplained fatigue has a lifetime
prevalence rate of 15%.

Neurasthenia
The term neurasthenia was coined in the 1880s to describe chronic fatigue, and
neurasthenia still remains a separate diagnosis in the International Statistical Clas-
sification of Diseases and Related Health Problems, 10th Revision (ICD-10). It is de-
fined as persistent and distressing complaints of increased fatigue after mental
effort, or persistent and distressing complaints of body weakness and exhaustion
after minimal effort, with accompanying somatic symptoms in the absence of a
depressive or anxiety disorder (World Health Organization 1992). Although sig-
nificant overlap exists between fatigue and psychiatric disorders, about 7% of
adults suffer from fatigue without psychiatric symptoms (Harvey et al. 2009).

Differential Diagnosis
Although only one-half of primary care patients receive a diagnosis that ex-
plains their fatigue (Nijrolder et al. 2009), a broad range of medical conditions
may result in fatigue. These include congestive heart failure, cancer, chronic
obstructive pulmonary disease, renal failure, HIV, sleep disorders, musculo-
skeletal disorders, and depression (Evans and Lambert 2007). (See Table 21–1
for a longer list.)

Higher Rates of Psychiatric Illness

In the general population, people with fatigue are more likely to have experi-
enced current and lifetime episodes of depression, anxiety, and somatization
compared with people without fatigue (Walker et al. 1993). In primary care
settings, most patients with chronic fatigue (60%) and chronic fatigue syn-
drome (75%) have a current psychiatric disorder (Wessely et al. 1996).

Premorbid Predictors of Chronic Fatigue

Higher emotional instability (an individual’s tendency to experience psycho-
logical distress) and self-reported stress in the premorbid period have been
shown to increase the risk for chronic fatigue–like illness, and the effect ap-
pears to be modulated by genetic factors (Kato et al. 2006). Excessive child-
hood energy and adult obesity appear to be risk factors for fatigue without
comorbid psychiatric illness (Harvey et al. 2009).
 Fatigue and Fibromyalgia 375

Table 21–1. Differential diagnosis for chronic fatigue

Cardiopulmonary Neoplastic-hematological
Chronic congestive heart failure Anemia
Chronic obstructive pulmonary Occult malignancy
disease Neurological
Endocrine-metabolic Multiple sclerosis
Adrenal insufficiency Poststroke
Apathetic hyperthyroidism Spinal stenosis
Chronic renal failure Pharmacological
Diabetes mellitus Antidepressants
Hepatic failure Antihypertensives
Hypercalcemia Benzodiazepines
Hypothyroidism Chemotherapeutic agents
Idiopathic Opioids
Chronic fatigue syndrome Statins
Fibromyalgia Psychiatric
Idiopathic chronic fatigue Anxiety
Infectious Depression
Cytomegalovirus Somatoform disorders
Endocarditis Sleep disorders
Hepatitis C Obstructive sleep apnea
HIV
Lyme disease Rheumatological
Mononucleosis Polymyalgia rheumatica
Occult abscess Rheumatoid arthritis
Systemic lupus

Chronic Fatigue Syndrome

History
Chronic fatigue syndrome (CFS) was named in 1988, but CFS-like cases were
described over a century ago. Over the last several decades, controversies have
existed about whether CFS is a real condition, and about its pathogenesis and
treatment. Debate over whether it is organic or psychogenic has given rise to a
dichotomous approach that does not integrate the biological, psychological,
and social aspects of the illness, as required for effective treatment. Consensus
criteria published in 1994 require that patients have clinically evaluated, un-
376 Clinical Manual of Psychosomatic Medicine

explained, persistent, or relapsing fatigue plus four or more specifically de-

fined associated symptoms (Fukuda et al. 1994) (see Table 21–2).

Epidemiology
Although chronic fatigue is common in medical patients, CFS is relatively un-
common, accounting for only 1%–9% of chronic fatigue patients, with a prev-
alence of 0.3% (Bates et al. 1993; Prins et al. 2006). Seventy-five percent of CFS
patients are female, and the mean age at onset is between 29 and 35 years; the
mean duration of illness is 3–9 years. Patients with psychiatric illness have a
poorer prognosis, whereas patients who have less severe fatigue at baseline, dem-
onstrate a sense of control over their symptoms, and do not attribute their illness
to a physical cause have a better prognosis (Cairns and Hotopf 2005).

Etiology
Predisposing factors. Twin studies have shown a familial predisposition to
CFS, but no specific genetic abnormalities have been found. Personality char-
acteristics such as neuroticism and introversion may be risk factors (Prins et al.
2006).
Precipitating factors. Some evidence suggests that infection is associated
with the development of CFS. Stressful life events may also precipitate the dis-
order (Prins et al. 2006).
Perpetuating factors. Immunological factors, including cytokines, neuro-
endocrine changes, sleep abnormalities, and chronic infection, may have a
role in maintaining the illness. Psychological factors, such as a strong belief in
a physical cause of the illness, a focus on bodily sensations, and a sense of loss
of control, have been found to perpetuate the symptoms (Prins et al. 2006).

Treatment
Cognitive-behavioral therapy. Cognitive-behavioral therapy (CBT), which
focuses on changing condition-related thoughts and behaviors, and teaches pa-
tients how to control their symptoms, is effective in treating CFS (Prins et al.
2006). In a 5-year follow-up study, 70% of patients receiving CBT had sus-
 Fatigue and Fibromyalgia 377

Table 21–2. International Chronic Fatigue Syndrome Study Group

consensus criteria for chronic fatigue syndrome
1. Clinically evaluated, unexplained, persistent, or relapsing fatigue that is of new or
definite onset; is not the result of ongoing exertion; is not alleviated by rest; and
results in substantial reduction in previous levels of occupational, educational,
social, or personal activities
and
2. Four or more of the following symptoms that persist or recur during 6 or more
consecutive months of illness and that do not predate the fatigue:
• Self-reported impairment in short-term memory or concentration
• Sore throat
• Tender cervical or axillary nodes
• Muscle pain
• Multijoint pain without redness or swelling
• Headaches of a new pattern or severity
• Unrefreshing sleep
• Postexertional malaise lasting ≥24 hours

Source. Adapted from Fukuda et al. 1994.

tained improvement, compared with 35% of patients treated with relaxation

therapy (Deale et al. 2001).
Graded exercise therapy. Graded exercise therapy is an educational inter-
vention that encourages graded activity, based on a physiological model of de-
conditioning. A randomized controlled trial (RCT) demonstrated continued
benefit for patients with CFS 2 years following treatment (Powell et al. 2004).
Other treatments. Insufficient evidence is available to support the use of
pharmacological agents, supplements, or alternative treatments for CFS (Whit-
ing et al. 2001), although treatment of comorbid psychiatric illness is impor-
tant. Data do not show benefit from treatment of CFS with modafinil (Randall
et al. 2005), methylphenidate (Blockmans et al. 2006), or antidepressants (Ver-
coulen et al. 1996).
378 Clinical Manual of Psychosomatic Medicine

Fibromyalgia
Epidemiology
The prevalence of fibromyalgia syndrome (FMS) in the United States is ap-
proximately 2%, and FMS is at least six times more common in women than
in men (Wolfe et al. 1995). The prevalence increases with age, and patients
who present with FMS are, on average, 10 years older than patients who pre-
sent with CFS. FMS is more prevalent in individuals with less education and
lower socioeconomic status (White et al. 1999).

Pathophysiology
Controversy exists about whether FMS is a distinct disorder or the manifes-
tation of an underlying malady ranging from inflammatory arthritic disease to
depression (Hauser et al. 2009). A particular pathology has not been found for
FMS. One potential explanatory mechanism is that individuals with FMS ex-
perience pain differently than do those without FMS. FMS has been consid-
ered a rheumatological disease, in part because of prominent muscle and joint
pain, although evidence has not supported the presence of musculoskeletal
abnormalities. Recent literature has focused on abnormal central pain pro-
cessing rather than dysfunction in the peripheral tissues (Abeles et al. 2007).

Classification Criteria
The American College of Rheumatology listed the following classification cri-
teria (Wolfe et al. 1990):

1. History of widespread pain involving all four limbs and the trunk
2. Pain in at least 11 of 18 specified tender point sites with digital palpation

Clinical Manifestations
Despite the American College of Rheumatology’s criteria (Wolfe et al. 1990),
the syndrome is associated with a myriad of other symptoms, the most com-
mon of which are fatigue, poor sleep quality, and morning stiffness (Abeles et
al. 2007). Frequent neurological symptoms include poor balance or coordi-
nation, tingling or weakness in the arms or legs, numbness, and photophobia
(Watson et al. 2009). The majority of patients have headaches (Marcus et al.
 Fatigue and Fibromyalgia 379

2005), and many have a variety of other pain symptoms, including abdominal
and pelvic pain. Additional symptoms such as night sweats, sexual dysfunc-
tion, dyspnea, dysphagia, and urinary urgency may occur.

Increased Rates of Psychiatric Disorders

Depression
Depression is prevalent in patients with FMS and may exceed 50% (Okifuji et
al. 2000). Both the rate and familial prevalence of major affective disorder are
significantly higher in patients with fibromyalgia than in patients with rheu-
matoid arthritis (Hudson et al. 1985). Concurrent depressive disorders may
be independent of the cardinal features of FMS (i.e., pain severity and hyper-
sensitivity to pressure pain), but depression nonetheless influences the effects
of FMS symptoms on patients’ daily lives and functional activities (McBeth
and Silman 2001; Okifuji et al. 2000).
Anxiety Disorders
Anxiety disorders are twice as prevalent in patients with FMS as in control pa-
tients with chronic pain (McBeth and Silman 2001). Patients with FMS have
higher rates of posttraumatic stress disorder (PTSD) and are more likely to
have experienced childhood trauma or abuse. Patients with FMS who have
PTSD-like symptoms have been shown to have significantly greater levels of
pain, emotional distress, and disability than FMS patients without those
symptoms (Sherman et al. 2000).
Somatization and Onset of Widespread Body Pain
The multiple pain complaints of patients diagnosed with fibromyalgia may
represent a somatization process. One prospective study demonstrated that
the strongest predictor of the development of chronic widespread pain in pa-
tients who had no pain at baseline was high scores on measures of somatiza-
tion and maladaptive coping mechanisms (McBeth et al. 2001).
Shared Genetic Risk Factors for Fibromyalgia and Major Depressive Disorder
Family aggregation studies suggest that patients with fibromyalgia and major
depressive disorder may have genetically or biologically mediated vulnerabil-
ity to respond to stressful life events with pain-related and affective symptoms
(Kato et al. 2009; Raphael et al. 2004).
380 Clinical Manual of Psychosomatic Medicine

Pharmacological Treatment
Antidepressants
On the basis of a meta-analysis, researchers concluded that strong evidence ex-
ists for the efficacy of antidepressants to reduce pain, sleep disturbance, and
depressed mood, as well as to improve health-related quality of life (Hauser et
al. 2009). The data on the long-term effects of antidepressants are insufficient
to draw conclusions (Uceyler et al. 2008).
Tricyclic antidepressants. The most robust evidence for medication efficacy
in FMS is for the tricyclic antidepressants (TCAs). Amitriptyline, the most
widely studied TCA, has demonstrated effects on sleep, fatigue, and pain. Most
studies report the use of low dosages of amitriptyline, between 12.5 and 50 mg/
day; TCAs have been shown to have an effect on fibromyalgia independent of
depressive symptoms. Adverse effects are the primary reason for not increasing
the dosage to achieve serum levels in the therapeutic window for depression
(Goldenberg et al. 2004; Hauser et al. 2009; Perrot et al. 2008). Cyclobenza-
prine is a muscle relaxant with a tricyclic structure, and the evidence is strong for
its efficacy at dosages of 10–40 mg/day (Goldenberg et al. 2004).
Serotonin-norepinephrine reuptake inhibitors. The serotonin-norepineph-
rine reuptake inhibitors (SNRIs) duloxetine and milnacipran have both been ap-
proved by the U.S. Food and Drug Administration (FDA) for the management of
FMS. Both are significantly more effective than placebo for pain, dysfunction,
dyssomnia, and fatigue. Duloxetine 60–120 mg/day and milnacipran 100–200
mg/day are equally effective for pain (Perrot et al. 2008). The analgesic effect ap-
pears to be unrelated to the antidepressant effects and may be due to the modu-
lation of pain pathways in the central nervous system. Venlafaxine has not been
studied as extensively as duloxetine and milnacipran for the treatment of FMS.
Selective serotonin reuptake inhibitors. In the meta-analysis by Hauser et
al. (2009), the effect sizes for the selective serotonin reuptake inhibitors were
smaller than for the TCAs, but a definitive conclusion could not be made for
superior efficacy of one class of antidepressant over another.

Anticonvulsants
Pregabalin and gabapentin are anticonvulsants with analgesic effects thought
to be mediated through the α2δ protein, a subunit of voltage-dependent cal-
 Fatigue and Fibromyalgia 381

cium channel neurons. These medications modulate the influx of calcium

ions and reduce the synaptic release of neurotransmitters believed to have an
effect in pain processing. Pregabalin is approved by the FDA for treatment of
FMS, and is associated with improvements in pain, sleep, health-related qual-
ity of life, and global measures (Crofford et al. 2005). The FDA-indicated
dosage of pregabalin is 150–225 mg twice daily. An RCT of gabapentin for
FMS used flexible dosing of 1,200–2,400 mg/day (Arnold et al. 2007).

Analgesic Medications
Modest evidence supports the efficacy in patients with FMS of tramadol ad-
ministered with or without acetaminophen in dosages of 200–300 mg/day.
The long-term efficacy and tolerability is unknown, however, and the risk of
abuse needs to be considered. Nonsteroidal anti-inflammatory drugs alone are
not effective, although they may be useful when combined with TCAs. No
RCTs of opioids in the treatment of FMS have been reported (Goldenberg et
al. 2004).

Nonpharmacological Treatments
Exercise
Substantial evidence indicates that cardiovascular exercise is effective for in-
creasing aerobic performance, raising tender-point pain pressure thresholds,
and decreasing pain in patients with FMS. Exercise combined with education
has shown improvement in global well-being, fatigue, sleep, and aerobic per-
formance (Goldenberg et al. 2004).

Cognitive Therapies
In RCTs of CBT, patients with FMS have experienced improved pain, mood,
fatigue, and function, and the effects are often sustained beyond 6 months
(Goldenberg et al. 2004).

Multidisciplinary Treatment
Treatment that combines education, CBT, relaxation training, and exercise
have demonstrated beneficial effects on patient self-efficacy and pain, and re-
duced physician-rated disease severity. Further studies are needed to evaluate
programs that combine medication and nonpharmacological treatment (Gold-
enberg et al. 2004).
382 Clinical Manual of Psychosomatic Medicine

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Arnold LM, Goldenberg DL, Stanford SB, et al: Gabapentin in the treatment of fi-
bromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial.
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Cairns R, Hotopf M: A systematic review describing the prognosis of chronic fatigue
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Hauser W, Bernardy K, Uceyler N, et al: Treatment of fibromyalgia syndrome with
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 22
Gastroenterology

The brain-gut axis challenges the physician, whether psychiatrist or endos-

copist. Not long ago, peptic ulcer disease was emblematic of psychosomatic
illness, but stress and conflict have been displaced by Helicobacter pylori and
nonsteroidal anti-inflammatory drugs (NSAIDs) as the causes of peptic ul-
cers. Nevertheless, a patient’s biopsychosocial milieu may leave a morpholog-
ical trace in the pathologist’s description of a small bowel frozen section.
Childhood trauma may now find a muted voice in visceral hypersensitivity. In
one study, psychotherapy eased somatic symptoms in patients with severe ir-
ritable bowel syndrome (IBS), but psychological markers of distress changed
little (Creed et al. 2003). The brain-gut axis invites the consultation psychia-
trist’s study.

385
386 Clinical Manual of Psychosomatic Medicine

Oropharyngeal and
Upper Gastrointestinal Disorders
Even when they are not the primary reason for a psychiatric consultation re-
quest, oropharyngeal and upper gastrointestinal disorders are common co-
morbidities with psychiatric disorders.

Dysphagia
Dysphagia affects up to 10% of older adults, precipitated by several neurolog-
ical conditions (e.g., stroke, multiple sclerosis, Parkinson’s disease) and medica-
tions, including antipsychotics. In patients taking antipsychotics, management
requires lowering the dosage, switching to another agent, or discontinuing anti-
psychotics altogether. Benztropine and diphenhydramine are not helpful in re-
lieving antipsychotic-induced dysphagia (Dziewas et al. 2007).

Globus Hystericus
Globus hystericus is the persistent sensation of a lump in the throat. Despite
the condition’s name, careful ear, nose, and throat evaluation yields some mea-
sure of physiological abnormality in most patients (Leelamanit et al. 1996).
Although the time course varies, the condition is benign and almost always
gradually resolves in response to recommended treatment, reassurance, and,
in cases of concomitant panic disorder, anxiolytics.

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is common in North America and
Western Europe but rare elsewhere. Studies examining the association of
GERD with selective serotonin reuptake inhibitors (SSRIs), anxiety, and de-
pression have not had uniform results, although the larger, population-based
studies suggest independent increased risk with each of these variables (Jans-
son et al. 2007; van Soest et al. 2007). GERD patients who have a history of
sexual or physical abuse are more prone to bring their symptoms to medical
attention than those with no history of abuse (Mizyed et al. 2009).
 Gastroenterology 387

Noncardiac Chest Pain

Noncardiac chest pain occurs in up to 25% of the population annually and is
often nearly identical to the pain of cardiac ischemia, prompting many emer-
gent assessments. Although panic disorder and other anxiety disorders are
more common in patients with noncardiac chest pain than in the general pop-
ulation (Fass and Dickman 2006), other factors, such as esophageal hypersen-
sitivity, are also likely to play a role.

Hyperemesis Gravidarum
Hyperemesis gravidarum requires sufficient nausea and vomiting in preg-
nancy to provoke ketonuria and weight loss; it affects up to 2% of women. In
years past, this diagnosis was often attributed to ambivalence regarding the
pregnancy, but evidence does not support this (Kim et al. 2009). Medical in-
terventions include intravenous hydration and pharmacotherapy (Bottomley
and Bourne 2009).

Anticipatory Nausea and Vomiting

Anticipatory nausea and vomiting is most commonly associated with chemo-
therapy but can also occur in association with any other situation or condition
that was previously linked in the patient’s experience with nausea and vomit-
ing. Behavioral interventions are the most helpful, benzodiazepines are some-
times effective, and conventional antiemetics are not at all useful (Matteson et
al. 2002).

Dyspepsia and Peptic Ulcer Disease

Dyspepsia and peptic ulcer disease have prompted psychiatric investigation
for more than 80 years; multiple factors have been identified (e.g., H. pylori,
NSAIDs, alcohol, nicotine) and new treatments introduced (e.g., proton-
pump inhibitors). Nonetheless, stress and anxiety continue to be associated
with the occurrence of dyspepsia and peptic ulcer disease, underscoring the
value of including stress reduction and anxiolytic strategies in any treatment
plan (Crone and Dobbelstein 2011).
388 Clinical Manual of Psychosomatic Medicine

Irritable Bowel Syndrome

IBS is the presence of abdominal discomfort or pain that has occurred for 12 or
more weeks (not necessarily consecutive) in the prior 12 months and is char-
acterized by at least two of the following: 1) onset is associated with a change in
the frequency of bowel movements (diarrhea or constipation); 2) onset is asso-
ciated with a change in the form of the stool (loose, watery, or pellet-like); and
3) the discomfort or pain is relieved with defecation. Patients commonly com-
plain of feelings of abdominal distension or incomplete evacuation, as well as
unusual straining or, conversely, urgency (Creed and Olden 2005).

Epidemiology
The prevalence of IBS is uncertain because the spectrum of severity is broad and
because existing studies have examined variable age groups with different diag-
nostic criteria. Also, only a portion of people with IBS seek medical attention.
One U.S. householder survey identified a prevalence of about 10% (Drossman
et al. 1993). The association of IBS with the following extraintestinal nonpsy-
chiatric disorders is high: temporomandibular joint disorder (65%), chronic fa-
tigue syndrome (50%), chronic pelvic pain (50%), fibromyalgia (50%), and
interstitial cystitis (30%) (Riedl et al. 2008; Whitehead et al. 2002).

Psychiatric Issues
Psychiatric issues are both implicit and explicit:

• Patients with IBS make two to three times as many health care visits per
year as control subjects. The majority of these visits are for extraintestinal
somatic complaints, reflecting significant distress and erosion of quality of
life (Whitehead et al. 2002).
• Stress is a common forerunner of IBS and an important predictor of out-
come for patients with IBS. Interpersonal stresses are important despite a
frequent inclination among these patients to discount the relevance of
such tensions (Crone and Dobbelstein 2011).
• Past sexual and physical abuse is associated with up to a threefold increase
in incidence of IBS among individuals reporting past sexual abuse (Dross-
man et al. 1995).
 Gastroenterology 389

• Panic disorder, anxiety, and depression are reported in 50%–60% of pa-

tients with IBS seeking specialty care, with a trend toward anxiety in initial
presentations but depression in those who have sought medical attention
over time (Creed and Olden 2005).

Management
Methodological complexities prevent clear conclusions about the manage-
ment of IBS, but the following considerations may serve as a starting point for
a clinician’s decision making:

• Cognitive-behavioral therapy is more effective than education and may be

especially practical when high anxiety is present (Drossman et al. 2003).
• Interpersonal psychotherapy may be particularly apt for individuals who
have experienced sexual abuse (Creed et al. 2003).
• Tricyclic antidepressants are more suitable for depressed patients with
diarrhea-predominant IBS; adherence must be monitored to assess and
ensure efficacy, because side effects often prompt discontinuation (Dross-
man et al. 2003; Ford et al. 2009).
• SSRIs hold an advantage for depressed patients with constipation-
predominant IBS (Creed et al. 2003). Paroxetine may be an exception due
to its anticholinergic activity.
• When pain is the primary target symptom for an antidepressant, the cli-
nician should explain this use to the patient to eliminate the risk of dis-
continuation when the patient is subsequently displeased to discover that
the medication prescribed is an antidepressant (Creed and Olden 2005).

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of conditions that include
Crohn’s disease, ulcerative colitis, and the less common collagenous colitis,
lymphocytic colitis, and microscopic colitis. The etiologies are cryptic but ap-
pear to involve the confluence of genetic and environmental factors that pro-
duce a grossly magnified intestinal inflammatory response in at-risk individuals
(Kucharzik et al. 2006). The linkage between IBD and psychiatric disorders
may have reciprocal elements: not only is IBD associated with increased anxi-
390 Clinical Manual of Psychosomatic Medicine

ety and depression, but these conditions are sometimes associated with in-
creased severity of IBD signs and symptoms. Recent attention has addressed
whether dysfunctional neuroimmunoregulatory circuits form a common path-
way for both IBD and depression (Graff et al. 2009).

Epidemiology
Although subclinical cases of ulcerative colitis are often attributed to infectious
colitis, the annual incidence of ulcerative colitis has remained fairly stable in the
United States at 10–12 per 100,000. In sharp contrast, the annual incidence of
Crohn’s disease has increased steadily as society has modernized and is at 6–8 per
100,000. The association between societal development and the increasing prev-
alence of IBD has been consistently and recurrently observed throughout the
world (Shanahan and Bernstein 2009; Thia et al. 2008). Both ulcerative colitis
and Crohn’s disease have a bimodal distribution, with peak incidences in the sec-
ond and third decades, and again in the sixth and seventh decades.

Psychiatric Issues
Comorbid Anxiety and Depression
The rigor of studies exploring the prevalence of anxiety and depression in pa-
tients with IBD has improved substantially in the past 10 years. Conserva-
tively, depression occurs at least twice as frequently in patients with IBD as in
general community samples. Although anxiety occurs less often than depres-
sion in patients with IBD, anxiety is still more prevalent in IBD patients than
in the general community. Earlier studies suggested that anxiety may occur
more often with Crohn’s disease and depression with ulcerative colitis, but the
majority of more recent studies that evaluated these inflammatory disorders
separately found Crohn’s disease and ulcerative colitis to be comparable in re-
gard to psychiatric comorbidity. Similarly, the rates of psychiatric disorders in
patients with IBD are roughly equivalent to those in patients with several
other chronic medical illnesses, such as diabetes mellitus and rheumatoid ar-
thritis (Graff et al. 2009).

Anxiety and Depression as Potential Risk Factors for IBD Onset

No definitive evidence indicates that either anxiety or depression raises the
risk of IBD onset, but some studies have noted relationships that warrant con-
 Gastroenterology 391

tinued exploration (Graff et al. 2009). For example, the onset of IBD symp-
toms occurred earlier in patients with lifetime mood or anxiety disorders, and
the majority of these patients experienced the psychiatric disorders 2 years or
more before IBD was established (Walker et al. 2008).

Anxiety and Depression as Risk Factors for IBD Exacerbation

Moderate evidence suggests that both anxiety and depression are often inten-
sified during IBD symptom flares. A small body of prospective literature in-
dicates that depression is associated with higher IBD activity, shorter intervals
until IBD relapse, and less chance of remission with infliximab treatment
(Mardini et al. 2004; Mittermaier et al. 2004; Persoons et al. 2005).

Psychiatric Sequelae of Treatment

Corticosteroids are commonplace among the salicyclates and immunomodu-
lators used to treat IBD. High dosages of corticosteroids may be required, but
sustained high dosing is rarely essential. In one study, 50% of patients receiv-
ing daily prednisone ≥20 mg experienced psychiatric symptoms, and 10% of
those were hospitalized for either mania or depression (Fardet al al. 2007).
The incidence of adverse psychiatric events is dose related. Mania is more
likely early in treatment, whereas depression more commonly emerges later,
including during the tapering phase (Graff et al. 2009).

Management
Screening for Anxiety and Depression
Ongoing active assessment for psychiatric comorbidity in patients with IBD is
important because of the association between IBD flares and the occurrence
of anxiety and depression, as well as the risk of decreased treatment adherence
by patients who are depressed (Nigro et al. 2001).

Pharmacological Versus Psychological Treatment

Pharmacological agents are often prescribed by primary care or gastroenterology
specialists, sparing the patient a psychiatric referral. The incidence of relapse is
higher, however, when patients discontinue medication than when they stop psy-
chological therapies, and many patients with IBD do not wish to add another
medication to their daily regimen. Psychotherapy has the disadvantage of dimin-
ished access and potentially higher cost. Because adherence may prove an impor-
392 Clinical Manual of Psychosomatic Medicine

tant determinant of efficacy, the clinician and patient should discuss the treatment
options and proceed with the patient’s preferred form of care (Fotaki et al. 2008;
Graff et al. 2009). The following information may help with the choice:

• SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) offer rel-

ative safety and efficacy but have a higher incidence of gastrointestinal side
effects, including nausea and diarrhea, that can impact quality of life for pa-
tients with IBD. The increase in upper gastrointestinal bleeding with SSRIs
and SNRIs can be reduced by concomitant acid-suppressing medications;
however, in one study, concomitant NSAIDs increased the risk of gas-
trointestinal bleeding eightfold (de Abajo and Garcia-Rodriguez 2008).
• Bupropion and mirtazapine have different side-effect profiles than the
SSRIs and SNRIs. Bupropion does not interfere with sexual function, an
issue that can be of particular importance for some IBD patients for whom
treatment has introduced challenges with intimacy (Graff et al. 2009).
Weight gain, desired by some but not all patients with IBD, is more likely
with mirtazapine.
• Psychological modalities, particularly cognitive-behavioral therapies, have
repeatedly been found to reduce anxiety and depression and to improve
overall function in patients with IBD. Although unequivocal evidence of
reduction in IBD severity has been more elusive, the psychological bene-
fits have persisted in 12-month follow-ups (Graff et al. 2009).

Hepatitis C Virus
Hepatitis C virus (HCV), whose existence was proved in 1989, is the most
common blood-borne infection in the United States.

Epidemiology
An estimated 3.2 million persons in the United States and as many as 300 million
worldwide have HCV, and no vaccine is available to protect against infection. The
incidence declined throughout the 1990s but has plateaued since 2003. HCV is
the major cause of chronic liver disease and hepatocellular carcinoma, as well as a
leading reason for liver transplantation. Intravenous drug use remains the most
common risk factor; transmission requires percutaneous or mucosal exposure.
 Gastroenterology 393

Psychiatric Issues
Psychiatric issues, including depression, anxiety, fatigue, irritability, and neuro-
cognitive complaints, are common among patients with chronic HCV.

• Intravenous drug use is common among individuals with high psychiatric

comorbidity, including other substance abuse, mood disorders, and psy-
chotic disorders, who are later infected with HCV (Loftis et al. 2006).
• HCV replication in the central nervous system is associated with changes in
frontal white matter neurotransmitter levels, which are correlated with im-
paired attention and concentration (Foster 2009). HCV also appears to stim-
ulate increased inflammatory cytokines and tumor necrosis factor, which are
associated with the “sickness behavior” syndrome (Quelhas and Lopes 2009).
• Medical complications and comorbidities, including cirrhosis, diabetes
mellitus, hepatocellular carcinoma, and coinfection with HIV or hepatitis
B virus, significantly erode health-related quality of life (Nash et al. 2009).
• Interferon-α is associated with depression, fatigue, anxiety, and irritability
in 30%–80% of patients (Schaefer and Mauss 2008).

Management
Management of patients with HCV requires anticipatory vigilance because
the incidence of psychiatric problems is high and the consequences of inade-
quate or absent treatment may include diminished adherence to an antiviral
regimen, thereby magnifying the eventual decay in overall health. Most ad-
verse effects of interferon-α occur in the first 3 months of treatment, leading
some intravenous drug users to erroneously conclude that they are experienc-
ing withdrawal effects and to return to substance abuse. This negative cascade
may warrant preventive initiation of an SSRI alongside or even before inter-
feron-α therapy begins (Schaefer and Mauss 2008).

Other Conditions
Hepatic Encephalopathy
Hepatic encephalopathy may appear much like delirium in the context of
known acute or chronic liver disease; it ranges in severity from subtle confusion
394 Clinical Manual of Psychosomatic Medicine

to coma. Possible contributors are numerous, and the workup is the same as
with delirium. The diagnosis requires the exclusion of other causes. Although
serum ammonia is often elevated and lactulose is commonly prescribed, some
thoroughly encephalopathic patients will have normal ammonia levels. The
cornerstone of treatment is the correction of any identifiable causal factor
(Sundaram and Shaikh 2009).

Drug-Induced Hepatic Injury

Drug-induced hepatic injury may occur with most psychotropic medications,
but the risk is very low. The idiosyncratic reactions range in severity from un-
noticed to catastrophic, cannot be predicted, are not dose dependent, occur at
variable intervals following drug initiation, and almost always resolve after the
offending agent is discontinued. Women are at increased risk, but individuals
with comorbid liver disease are not, although the latter have less capacity to
tolerate the added compromise of liver function. Potential culprit medications
should be discontinued if a patient’s serum alanine transferase exceeds three
times normal, but routine prophylactic monitoring in otherwise healthy in-
dividuals is not recommended (Crone and Dobbelstein 2011).

Drug-Induced Pancreatic Injury

Drug-induced pancreatic injury has been reported, although rarely, in pa-
tients taking antipsychotics, anticonvulsants, and antidepressants, irrespective
of class. The mechanism of causation is not known and is not dose dependent
but usually occurs in the early weeks following drug initiation. Patients with
multiple concomitant medications, as well as individuals with cancer, Crohn’s
disease, and HIV, are at higher risk. Prompt discontinuation of the drug typ-
ically leads to resolution; rechallenge with the same drug is not recommended
(Crone and Dobbelstein 2011).

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 23
HIV and AIDS

In 1981, the first cases of AIDS (acquired immunodeficiency syndrome)

were reported to the CDC (then called the Center for Disease Control; now
known as the Centers for Disease Control and Prevention). Since that time,
the HIV (human immunodeficiency virus) epidemic has expanded to become
one of the greatest public health challenges, both nationally and globally. The
millionth case of AIDS in the United States occurred in 2007 (CDC 2008).
Despite significant advances in HIV testing, prevention, and treatment in the
United States, the human toll has been substantial.

Epidemiology
Cases of HIV/AIDS
From 2004 through 2007, the estimated number of newly diagnosed HIV/
AIDS cases in the 34 states that have confidential name-based HIV reporting
increased 15% (CDC 2008). In 2007, the estimated rate in the 34 states was
21.1 per 100,000 population.

399
400 Clinical Manual of Psychosomatic Medicine

Age Group
From 2004 through 2007, the estimated number of newly diagnosed HIV/
AIDS cases decreased among children (less than 13 years of age) and persons
ages 30–39 years. The estimated number of HIV/AIDS cases remained stable
among persons ages 13–14 years and increased among persons ages 15–29 and
ages 40 and older (CDC 2008).

Race and Ethnicity

From 2004 through 2007, the estimated number of newly diagnosed HIV/
AIDS cases increased among all races and ethnic groups (CDC 2008). Blacks
accounted for 51% of all HIV/AIDS cases diagnosed in 2007, and rates of
cases in the black population were over eight times higher than in the white
population and three times higher than in the Hispanic/Latino population.

Sex
From 2004 through 2007, the estimated number of newly diagnosed HIV/
AIDS cases increased approximately 18% among males and 8% among fe-
males (CDC 2008). Males accounted for 74% of all HIV/AIDS cases among
adults and adolescents.

Transmission Category
From 2004 through 2007, the estimated number of newly diagnosed HIV/
AIDS cases increased among men who have sex with men and among men
and women with high-risk heterosexual contact. Numbers remained stable
among injection drug users (CDC 2008). Men who have sex with men and
persons exposed through high-risk heterosexual contact accounted for 53%
and 32%, respectively, of all HIV/AIDS cases diagnosed.

Progression to AIDS
Of all HIV infections diagnosed in 2006 in the 34 states with confidential
name-based HIV reporting, 36% progressed to AIDS within 12 months after
HIV infection was diagnosed. AIDS was diagnosed within 12 months after
the diagnosis of HIV infection for larger percentages of persons ages 35 years
and older, Hispanics/Latinos, male injection drug users, and males with HIV
infection attributed to high-risk heterosexual contact (CDC 2008).
 HIV and AIDS 401

Survival After AIDS Diagnosis

Increase in Survival Over the Years
Survival from the year of diagnosis increased each year during the period
1998–2005; year-to-year improvements were smaller during the period
2001–2005. From 2003 through 2007, the estimated number of deaths of
persons with AIDS who resided in the 50 states and the District of Columbia
decreased 17% (CDC 2008).

Impact of Highly Active Antiretroviral Therapy

Major gains have occurred in treating HIV disease as a result of the effective-
ness of highly active antiretroviral therapy (HAART). AIDS is no longer one
of the top three causes of death in the United States (Halman et al. 2002). Pa-
tients with HIV disease as well as HIV specialists now generally perceive HIV
disease as a chronic medical condition rather than a relentlessly progressive in-
fection.

Psychiatric Manifestations
Neuropsychiatric Syndromes
Neuropsychiatric Symptoms
Neuropsychiatric complications in patients with AIDS include memory def-
icits, concentration impairment, dementia, psychomotor slowing, motor def-
icits, apathy, withdrawal, depression, and psychosis. In the late stages of the
disease, the following are common: disorientation, profound slowing, severe
dementia, focal neurological signs, secondary neurological disorders (e.g., tu-
mors, central nervous system [CNS] toxoplasmosis), seizures, and agitation.

Multiple Causes of Neuropsychiatric Syndromes

Patients with AIDS may have neuropsychiatric sequelae that are caused by pri-
mary effects of the virus itself; neurotoxic by-products of the immune re-
sponses to the virus; indirect consequences of systemic disease (e.g., hypoxia,
fatigue, malnutrition), intracranial tumors, or infections that occur as a result
of the immunocompromised state; and adverse effects of medications used to
treat CNS AIDS disorders.
402 Clinical Manual of Psychosomatic Medicine

Changes in Mental Status

HIV-related conditions that may present with changes in mental status include
HIV dementia, toxoplasmosis, cytomegalovirus, CNS lymphoma, cryptococ-
cal meningitis, and progressive multifocal leukoencephalopathy (Della Penna
and Treisman 2005).

Need for Aggressive Management

Unless the patient is near death from nonneurological causes, aggressive diag-
nostic workup and management are indicated when new neuropsychiatric
symptoms emerge in AIDS patients. Treatment is possible for many AIDS-
related CNS disorders, especially toxoplasmosis, herpes simplex infection,
and CNS lymphoma.

Adverse Effects of HIV/AIDS Medications

HIV/AIDS medications may have adverse effects that cause neuropsychiatric
symptoms. The frequency with which mental status changes are due to med-
ication side effects has increased. In more systemically ill patients, the use of
more medications—medications that are more effective at crossing the blood-
brain barrier and medications in combination with one another—has resulted
in neuropsychiatric syndromes. The most common psychiatric side effects are
asthenia, insomnia, depression, delirium, mania, and irritability. The symp-
toms are often mild and nonspecific, but some may become the focus of psy-
chiatric consultation.

Neuropsychiatric Syndromes in HIV Infection Without AIDS

Neuropsychiatric syndromes may occur in HIV-infected patients without
AIDS. Secondary psychiatric syndromes can occur in these patients without
AIDS, although less commonly than in patients with AIDS. When neuropsy-
chiatric findings occur shortly after infection, symptoms are those of acute viral
encephalitis. Neuropsychiatric findings in early presentations of HIV-related
dementing processes tend to involve subcortical, integrative, and executive
functions; these include visuospatial integration, visuospatial memory, reaction
time, verbal fluency, nonverbal fluency, problem solving, conceptual skills, set
shifting, concentration, speed of mental processing, and mental flexibility.
Language and related general intellectual skills are usually spared.
 HIV and AIDS 403

Psychiatric Conditions
Delirium
Up to half of AIDS patients who require skilled nursing care have at least one
episode of delirium documented (Uldall and Berghuis 1997). Patients with
HIV-associated dementia are at increased risk for delirium. Etiologies for de-
lirium that are common in HIV/AIDS patients are hypoxia with pneumocystis
pneumonia, malnutrition, CNS infections and neoplasms, systemic infections,
HIV nephropathy, and medication toxicity (especially polypharmacy) (Wat-
kins et al. 2011). Acute HIV infection itself may also cause an acute encepha-
lopathy (Bialer et al. 2000).

HIV-Associated Dementia
Risk factors. In the pre-HAART era, risk factors associated with develop-
ment of HIV-associated dementia included higher HIV ribonucleic acid
(RNA) viral load, lower educational level, older age, illicit drug use, and fe-
male sex. However, in the post-HAART era, depression is more predictive of
the severity of HIV-associated dementia (Watkins et al. 2011).
Pathophysiology. Mechanisms of neuronal death in HIV-associated de-
mentia are not clear, but possibilities include glutamate overstimulation, cere-
brospinal fluid HIV RNA, and presence of other substances associated with
dementia, including quinolinic acid, prostaglandins, and neopterin (Nebu-
loni et al. 2001).
Clinical characteristics. The most typical HIV-associated dementia presen-
tation is that of a subcortical dementia, with memory and psychomotor speed
impairment, apathy, and movement disorders. Late symptoms may include
worsened motor symptoms and accelerated memory impairment. Psychiatric
symptoms may occur as part of HIV-associated dementia, including depres-
sion, hypomania, impulsivity, and emotional lability.
Diagnosis. Magnetic resonance imaging (MRI) often shows significant
white matter lesions, as well as cortical and subcortical atrophy, in patients
with HIV-associated dementia (Watkins et al. 2011). Functional MRI in HIV-
positive patients may predate clinical signs or deficits on cognitive tests (Ernst
et al. 2002).
404 Clinical Manual of Psychosomatic Medicine

Depression
Depressive symptoms and depressive disorders are more common among
HIV-infected persons than in the general population. The cause-effect consid-
erations are complex: HIV disease and associated medical complications can
cause secondary mood syndromes, and depression is also a risk factor for be-
havioral disturbances that may increase exposure to HIV infection (Watkins et
al. 2011). In addition, fatigue may be confused with depression. In fact, in per-
sons with HIV, fatigue has been found to be more associated with depression
than with HIV disease progression.

Mania
Like depression, mania is more frequent in patients with AIDS than in the
general population (Halman et al. 1993). Mania or hypomania may be pri-
mary or secondary. Secondary mania in AIDS may present differently than
primary bipolar mania (Ellen et al. 1999); patients with secondary mania have
prominent irritable mood, cognitive changes, and psychomotor slowing, in-
stead of hyperactivity, severe presentation, and malignant course.

Substance Use Disorders

Substance abuse is a vector for the spread of HIV, and it is the psychiatric diag-
nostic category with the highest prevalence of HIV infection (Beyer et al.
2007). Patients with dual diagnoses (substance use disorders and other psy-
chiatric disorders) who also are infected with HIV are overrepresented in HIV
treatment. Neuropsychological tests suggest that substance abuse can contrib-
ute to cognitive decline in HIV-associated dementia. Substance use in general,
and cocaine use in particular, may augment HIV replication in the CNS and
increase HIV encephalopathy risk by rendering the blood-brain barrier more
permeable to HIV (Watkins et al. 2011). Substance use is also associated with
significantly diminished adherence to treatment regimens such as HAART
(Chander et al. 2006).

Anxiety Disorders
Substantial and consistent evidence indicates that anxiety, trauma, and stress-
ful events may negatively affect HIV disease progression by decreasing CD4
T lymphocytes, increasing viral load, and accelerating clinical decline and
mortality (Leserman 2008; Strachan et al. 2007). Posttraumatic stress disorder
(PTSD) may occur at increased rates in HIV-infected persons (Martinez et al.
 HIV and AIDS 405

2002). PTSD symptoms are associated with frequency of high-risk behaviors,

including prostitution, injection drug use, and unsafe sexual practices. PTSD
patients are at elevated risk for other anxiety disorders, depression, and sub-
stance abuse.

Personality Disorders
Prevalence rates of personality disorders among HIV-infected patients (20%–
35%) exceed rates found in the general population (10%) (Johnson et al.
1995). Personality disorders in this population are associated with higher rates
of substance abuse, sharing needles, risky sexual behaviors, frequent sex with
multiple partners, and treatment nonadherence.

Psychiatric Treatment
For the treatment and management of patients with HIV disease, the psychia-
trist must take into consideration a wide range of etiological factors, including
premorbid primary psychiatric disorders, disorders secondary to HIV-related
CNS infections, advanced systemic disease, and neuropsychiatric side effects of
commonly used HIV/AIDS medications (Halman et al. 2002). Advanced sys-
temic disease and HIV-1 CNS infection can constrain the pharmacotherapeutic
options available to the psychiatric consultant (Ferrando et al. 2010). Psycho-
therapeutic interventions must take into account the perspectives of patients
who come from communities that often have been marginalized, socially disen-
franchised, and impoverished. Management plans frequently require liaison
with community-based HIV/AIDS service organizations and highly diverse so-
cial and family support groups.

Delirium
Management of HIV-associated delirium, which is similar to that for delirium
in general, involves searching for etiologies and correcting them when possible,
behavioral and environmental interventions, and judicious pharmacotherapy
(see Chapter 7, “Delirium”). Low dosages of high-potency, or atypical, anti-
psychotics are used with some success, although this off-label use is based on
case reports and case series. Anticholinergic medications may worsen delirium;
patients with HIV-associated dementia should be assumed to be vulnerable to
extrapyramidal symptoms. Benzodiazepines may exacerbate delirium and
406 Clinical Manual of Psychosomatic Medicine

should be used with caution in patients who abuse drugs; however, benzodiaz-
epines may be necessary when a patient has a withdrawal delirium from alcohol
or sedative-hypnotics.

HIV-Associated Dementia
The impact of HAART on cognitive outcomes has not been as robust as its im-
pact on other AIDS-related conditions (Watkins et al. 2011). When combina-
tion antiretroviral therapy is administered, cognitive improvement appears to
be related to a medication’s CNS penetration index, which may vary by indi-
vidual patient for a given dosage (Cysique et al. 2009). Improvement may oc-
cur within weeks after initiating therapy and may be persistent over at least a
year. Benefit may be maximized by choosing antiretroviral medications that
reach therapeutic concentrations in the CNS.

Depression
Antidepressants
Antidepressants have good response rates. Antidepressant nonadherence is the
most common reason for ineffective medication response, and adverse effects
are the most common reason for nonadherence. Fortunately, selective seroto-
nin reuptake inhibitors (SSRIs) are generally well tolerated and effective in
HIV-related major depressive disorder, with a 60%–80% response rate and no
deleterious effects on immune status (Halman et al. 2002). Studies of antide-
pressant efficacy among HIV-infected patients, however, are notable for sub-
stantial placebo response and attrition (Rabkin et al. 1999), suggesting that
other factors are important, for example, the status of the doctor-patient re-
lationship.
Caution is required when SSRIs are used to treat depression in HIV/AIDS
patients. The dosing principle of starting low and increasing slowly applies.
Drug interactions can occur between SSRIs and some antiretroviral therapies
because of competition for cytochrome P450 3A3/3A4 metabolism. Because
citalopram and sertraline have little interaction with these enzymes, they are
preferred over other SSRIs in treating depression in HIV-positive patients re-
ceiving antiretroviral treatment. If used, fluoxetine or paroxetine should be
started at 10 mg/day and increased to the standard dosage after 7–10 days
(Halman et al. 2002).
 HIV and AIDS 407

Psychostimulants
Psychostimulants may have a role in the treatment of some patients. At low
dosages, both dextroamphetamine and methylphenidate have been reported in
case series to be effective for HIV-related major depression, as primary agents
(Fernandez and Levy 1992) or as adjuvant agents, with response rates up to
80%. They are especially effective for anergia, apathy, and anorexia. Some pa-
tients also report improved mood, attention, and concentration. Although
stimulants are not usually first-line treatments for major depression, they
should be considered as an adjunct or a substitute for conventional antidepres-
sants in patients with a predominance of apathy compared with sadness, and in
patients who are unable to tolerate the side effects of conventional antidepres-
sants. Stimulants should also be considered for depression in the terminally ill
patient with HIV who may not live long enough for a traditional antidepres-
sant to take effect. Psychostimulants should be used with caution in patients
who have motor problems.

Mania
Although mood stabilizers have not been systematically studied in patients
with HIV/AIDS, case reports suggest that traditional mood stabilizers, espe-
cially lithium, are not tolerated by patients with HIV/AIDS as well as they are
by physically healthy bipolar patients. Patients with HIV/AIDS have less tol-
erance for lithium’s adverse effects, including nausea, vomiting, diarrhea,
tremor, and cognitive changes. Antipsychotics, especially low-potency agents,
may also be poorly tolerated. Late-stage patients may be especially prone to
side effects of mood stabilizers and antipsychotics. Low initial dosages of any
psychiatric medications should be used, and titration should be slow. Valproic
acid and carbamazepine have been used successfully, but liver enzymes and he-
matopoietic markers should be monitored closely. Because of medication sen-
sitivities, many manic AIDS patients end up being treated with low-dosage,
high-potency antipsychotic monotherapy.

Substance Use Disorders

Substance use disorders must be aggressively treated because of their morbidity
and because of their associations with HIV-associated risk behaviors and nonad-
herence to treatment (Disney et al. 2006). An example of effective prevention is
408 Clinical Manual of Psychosomatic Medicine

the enrollment of opiate-dependent patients at risk for HIV infection into meth-
adone maintenance programs, resulting in sustained reductions in HIV risk and
lower incidence of HIV infection (Della Penna and Treisman 2005).

Posttraumatic Stress Disorder

Persons at risk for HIV infection and HIV-infected individuals should be rou-
tinely screened for PTSD and treated as needed (see Chapter 6, “Anxiety”). Ig-
noring PTSD has serious consequences for this population’s welfare and for
public health (Watkins et al. 2011) because of the association of PTSD with
poor health behaviors, psychiatric comorbidity, and high-risk sexual behaviors.

Personality Disorder
Treatment principles for patients with HIV/AIDS who present with person-
ality complications include a number of techniques from cognitive-behavioral
therapy and dialectical behavior therapy traditions (Watkins et al. 2011):

• Focus on the patient’s thoughts, not feelings.

• Use a behavioral contract for patient to improve adherence.
• Emphasize constructive rewards (e.g., money saved from not buying drugs
can be used for clothes or food).
• Use relapse prevention techniques to change habitual ways of behaving.
• Develop a coordinated treatment plan in concert with medical providers.

References
Beyer JL, Taylor L, Gersing KR, et al: Prevalence of HIV infection in a general psychi-
atric outpatient population. Psychosomatics 48:31–37, 2007
Bialer PA, Wallack JJ, McDaniel S: Human immunodeficiency virus and AIDS, in
Psychiatric Care of the Medical Patient, 2nd Edition. Edited by Stoudemire A,
Fogel BS, Greenberg D. New York, Oxford University Press, 2000, pp 871–887
Centers for Disease Control and Prevention: HIV/AIDS Surveillance Report, 2008.
Available at: www.cdc.gov/hiv/surveillance/resources/reports/2008report/web-
address.htm. Accessed January 1, 2011.
Chander G, Himelhoch S, Moore RD: Substance abuse and psychiatric disorders in
HIV-positive patients: epidemiology and impact on antiretroviral therapy. Drugs
66:769–789, 2006
 HIV and AIDS 409

Cysique LA, Vaida F, Letendre S, et al: Dynamics of cognitive change in HIV-positive

patients initiating antiretroviral therapy. Neurology 73:342–348, 2009
Della Penna ND, Treisman GJ: HIV/AIDS, in The American Psychiatric Publishing
Textbook of Psychosomatic Medicine. Edited by Levenson JL. Washington, DC,
American Psychiatric Publishing, 2005, pp 599–627
Disney E, Kidorf M, Koldner K, et al: Psychiatric comorbidity is associated with drug use
and HIV risk in syringe exchange participants. J Nerv Ment Dis 194:577–583, 2006
Ellen SR, Judd FK, Mijch AM, et al: Secondary mania in patients with HIV infection.
Aust NZ J Psychiatry 33:353–360, 1999
Ernst T, Change L, Jovicich J, et al: Abnormal brain activation on functional MRI in
cognitively asymptomatic HIV patients. Neurology 59:1343–1349, 2002
Fernandez F, Levy JK: Psychopharmacotherapy of psychiatric syndromes in asymp-
tomatic and symptomatic HIV infection. Psychiatr Med 9:377–394, 1992
Ferrando SJ, Levenson JL, Owen JA: Infectious diseases, in Manual of Psychopharma-
cology in the Medically Ill. Edited by Ferrando SJ, Levenson JL, Owen JA. Wash-
ington, DC, American Psychiatric Publishing, 2010, pp 371–404
Halman MH, Worth JL, Sanders KM, et al: Anticonvulsant use in the treatment of
manic syndromes in patients with HIV-1 infection. J Neuropsychiatry Clin Neuro-
sci 5:430–434, 1993
Halman MH, Bialer P, Worth JL, et al: HIV Disease/AIDS, in The American Psychi-
atric Publishing Textbook of Consultation-Liaison Psychiatry: Psychiatry in the
Medically Ill, 2nd Edition. Edited by Wise MG, Rundell JR. Washington, DC,
American Psychiatric Publishing, 2002, pp 807–851
Johnson JG, Williams JBW, Rabkin JG, et al: Axis I psychiatric symptomatology as-
sociated with HIV infection and personality disorder. Am J Psychiatry 152:551–
554, 1995
Leserman J: Role of depression, stress, and trauma in HIV disease progression. Psy-
chosom Med 70:539–545, 2008
Martinez A, Israelski D, Walker C, et al: Posttraumatic stress disorder in women at-
tending human immunodeficiency virus outpatient clinics. AIDS Patient Care
STDS 16:283–291, 2002
Metzger et al. 1998
Nebuloni M, Pellegrinelli A, Ferri A, et al: Beta amyloid precursor protein and patterns
of HIV p24 immunohistochemistry in different brain areas of AIDS patients.
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Rabkin JG, Wagner GJ, Rabkin R: Fluoxetine treatment for depression in patients
with HIV and AIDS: a randomized, placebo-controlled trial. Am J Psychiatry
156:101–107, 1999
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Strachan ED, Bennet WR, Russo J, et al: Disclosure of HIV status and sexual orien-
tation independently predicts increased absolute CD4 cell counts over time for
psychiatric patients. Psychosom Med 69:74–80, 2007
Uldall KK, Berghuis JP: Delirium in AIDS patients: recognition and medication fac-
tors. AIDS Patient Care STDS 11:435–441, 1997
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atric Publishing Textbook of Psychosomatic Medicine, 2nd Edition. Edited by Lev-
enson JL. Washington, DC, American Psychiatric Publishing, 2011, pp 637–665
 24
Obstetrics

Untreated maternal psychiatric illness has consequences not only for the
mother, but also for the developing fetus, the infant, and the child. The peak
incidence of affective disorders in women, at ages 25–44 years, coincides with
childbearing years. Most women with psychiatric disorders do not receive
mental health care regardless of pregnancy status (Vesga-Lopez et al. 2008).
Those women who do receive psychiatric treatment often discontinue taking
psychotropic medication while they are attempting to conceive, are pregnant,
or are breast-feeding. A careful risk-benefit analysis is needed as women and
their physicians consider the negative effects of untreated mental illness versus
the risk of exposure to psychotropics for the fetus and infant.

Epidemiology
Pregnancy and Childbirth
Pregnancy per se is not associated with an increased risk of most psychiatric
disorders. In pregnant and postpartum women, younger age, singleness, ex-
posure to traumatic or stressful life events, pregnancy complications, and

411
412 Clinical Manual of Psychosomatic Medicine

overall poor health increase the risk of psychiatric disorders (Vesga-Lopez et al.
2008). Childbirth is associated with an increased risk of inpatient psychiatric
readmission for mothers during the first postpartum month, but thereafter,
the rates decrease and nonmothers have a higher risk for readmission. A diag-
nosis of bipolar disorder is the strongest predictor of readmission during the
first postpartum month (Munk-Olsen et al. 2009).

Mood Disorders
An estimated 10%–15% of women experience depression during pregnancy,
the postpartum period, or both (Bennett et al. 2004; Gavin et al. 2005). Stud-
ies have suggested that the rate of mood disorders is similar in pregnant and
nonpregnant women, although a large national survey found that pregnant
women are significantly less likely than nonpregnant women to have a mood
disorder (Vesga-Lopez et al. 2008). Postpartum blues, characterized by labile
mood, irritability, and tearfulness, is a transient state that typically peaks at 3–
5 days postpartum and occurs in 50% of women (Miller 2002). The risk of
major depressive disorder appears to be increased in the postpartum period
(Vesga-Lopez et al. 2008).

Anxiety Disorders
Anxiety disorders are common during the perinatal period. Some studies re-
port higher rates of obsessive-compulsive disorder and generalized anxiety dis-
order in postpartum women (Ross and McLean 2006), but other data suggest
similar rates (Vesga-Lopez et al. 2008). Situational anxiety warrants consider-
ation, and inquiring about a history of negative obstetrical or other medical
experiences may help identify the source of anxiety or even of posttraumatic
stress disorder (PTSD) symptoms.

Substance Abuse
Alcohol use is less frequent among pregnant and postpartum women than
nonpregnant women, but illicit drug use is the same. Methamphetamine use
is rising among pregnant women and has become the primary substance for
which pregnant women enter inpatient substance abuse treatment, account-
ing for 25% of all admissions in 2006 (Terplan et al. 2009).
 Obstetrics 413

Postpartum Psychosis
Postpartum psychosis is a psychiatric emergency requiring hospitalization.
This diagnosis has garnered considerable attention because 1 in 25 mothers
with postpartum psychosis commits infanticide (Spinelli 2009). The majority
of women with postpartum psychosis have bipolar disorder. Clinically, the
presentation can be similar to delirium with cognitive dysfunction and disor-
ganization, including waxing and waning, bizarre behavior, delusions, and
impaired sensorium (Wisner et al. 1994). New-onset psychosis necessitates a
differential diagnostic evaluation comparable to that performed with a non-
gravid patient.
The following are major risk factors for postpartum psychosis (Jones and
Craddock 2001):

• History of psychosis following prior childbirth (relapse rates approach

70%)
• History of bipolar disorder
• Family history of postpartum psychosis

Schizophrenia
A variety of pregnancy, birth, and neonatal complications have been reported
for women with schizophrenia. Adverse outcomes include a higher incidence
of placental abruption, low-birth-weight infants, and increased risk of cardio-
vascular congenital anomalies (Jablensky et al. 2005).

Maternal Depression, Adverse Reproductive

Outcomes, and Comorbid Medical Problems
Preterm Delivery
The data are mixed regarding the association between depression during preg-
nancy and preterm delivery (Yonkers et al. 2009). One prospective study
found that infants exposed to either depression or selective serotonin reuptake
inhibitors (SSRIs) continuously across gestation were more likely to be born
preterm, with preterm birth rates of more than 20% (Wisner et al. 2009).
414 Clinical Manual of Psychosomatic Medicine

Comorbid Medical Illness

Comorbid medical illness may increase risk of depression. Postpartum depression
rates are higher among women with epilepsy, especially those who are multiparous
or receiving multiple antiepileptic drugs, than in the general population (Galanti
et al. 2009). Women with diabetes, even without a prior history of depression, had
twice the risk of developing postpartum depression during the year following de-
livery than women without diabetes (Kozhimannil et al. 2009).

Screening for Depression

Multiple depression screening instruments are easy to administer and require
less than 10 minutes to complete. The Edinburgh Depression Scale was de-
signed specifically for screening for depression in pregnancy and the postpar-
tum period. It has good sensitivity and specificity, and it is a reliable instrument
for repeated evaluations of depressive symptoms during pregnancy (Bunevicius
et al. 2009). Other instruments with high sensitivity are the Patient Health
Questionnaire–9 and the Postpartum Depression Screening Scale (American
College of Obstetricians and Gynecologists Committee on Obstetric Practice
2010).

Treatment of Depression and

Anxiety During Pregnancy
High Risk of Relapse With Antidepressant Discontinuation
Women with depression, including those who have a history of recurrent de-
pressive illness, are likely to discontinue antidepressant use during attempts to
conceive or after conception. Physicians must assist women in making an in-
formed choice not only about the risks of prenatal exposure to medication, but
also about the risk of relapse if treatment is discontinued. In a study of women
receiving antidepressant treatment for major depression prior to pregnancy,
45% of women relapsed during pregnancy, and among those who relapsed,
70% had discontinued antidepressant treatment and 25% had continued
treatment (Cohen et al. 2006). In the group who relapsed, 50% relapsed
within the first trimester and 90% by the end of the second trimester.
 Obstetrics 415

General Approach
For the drug-naïve patient with mild depressive symptoms, psychotherapy is
considered first-line treatment. Evidence supports the use of interpersonal
therapy to address grief, interpersonal role disputes, role transitions, and in-
terpersonal deficits (Spinelli and Endicott 2003). Minimal data exist on the
use of cognitive-behavioral therapy (CBT) for pregnant women, although its
efficacy has been established for other populations. The decision to use med-
ication is based on the severity of depression, the number and frequency of de-
pressive episodes, and the history of response to medication. Table 24–1 pro-
vides general guidelines for choosing an antidepressant medication for women
during pregnancy.

Pharmacological Management
The potential risks of in utero exposure to antidepressant medications depend
on numerous factors, including gestational age, duration of exposure, and co-
morbid factors. All psychotropic medications cross the placenta, although
umbilical cord concentrations of antidepressants and their metabolites are
lower than maternal concentrations (Hendrick et al. 2003).

Selective Serotonin Reuptake Inhibitors

Overall, limited evidence exists of teratogenic effects from SSRI use in preg-
nancy. Increased risks of congenital cardiac malformations (reported with pa-
roxetine), craniosynostosis, and omphalocele have been found, but the data are
mixed and absolute risk is low (Alwan et al. 2007; Louik et al. 2007). The risk
of pregnancy complications, such as miscarriage, preterm birth, and low birth
weight appears to be low, but these findings are controversial. Two prospective
studies have found an association between antidepressant use and preterm
birth (Suri et al. 2007; Wisner et al. 2009). Exposure to SSRIs late in pregnancy
has been associated with transient neonatal complications, including jitteri-
ness, mild respiratory distress, weak cry, and poor muscle tone. Limited data
suggest a possible association between maternal use of SSRIs in the latter half of
pregnancy and persistent pulmonary hypertension of the newborn, although
the absolute risk is small (6–12 affected infants per 1,000 exposed fetuses)
(Chambers et al. 1996, 2006). Gestational hypertension and preeclampsia
have been reported to occur more frequently in women exposed to SSRIs dur-
416 Clinical Manual of Psychosomatic Medicine

Table 24–1. Guidelines for medication use during pregnancy or

breast-feeding
1. Perform a risk-benefit analysis.
2. Document the mother’s problems in daily living and her ability to care for the
fetus/infant, target symptoms, and the rationale for medication use.
3. Record all drug exposures (prescribed, over-the-counter, herbal, and illicit)
during pregnancy and the postpartum period, if the patient is breast-feeding. Ask
about and document alcohol consumption during pregnancy.
4. Obtain informed consent. Discuss with the mother the risks and unknown
aspects of taking psychotropic medication while pregnant or breast-feeding, to
include the remote possibility of long-term effects on the child. Document this
discussion, and have the patient sign the informed consent, especially if the
patient insists on taking medications despite recommendations to the contrary
(e.g., patient has a severe, chronic psychotic illness that responds only to
clozapine and insists on breast-feeding despite recommendations against breast-
feeding while taking clozapine). If the patient’s capacity to make an informed
decision is influenced by the illness, have the spouse participate in the decision-
making process and have him also sign the informed consent.
5. Use a medication that has worked in the past, unless contraindicated.
6. Choose a medication that has some data rather than a novel compound with no
data.
7. Attempt monotherapy. Data on combination pharmacotherapy do not exist. Do
not forget that electroconvulsive therapy is the treatment of choice when a
woman has a psychotic depression.
8. While the patient is breast-feeding, try to avoid prescribing medications that
require invasive monitoring (e.g., clozapine).
9. Use the minimum effective dosage.
10. Urge the mother who is breast-feeding to take doses so that the medication level
in breast milk is minimized at the time the infant nurses (i.e., take medication
immediately after the infant nurses, or take dose immediately prior to infant’s
long afternoon nap).
Source. Reprinted from Llewellyn A, Stowe ZN: “Psychotropic Medications in Lactation.”
Journal of Clinical Psychiatry 59 (suppl 2):41–52, 1998. Used with permission.
 Obstetrics 417

ing late pregnancy, but a causal relationship has not been determined (Toh et
al. 2009).
Fluoxetine. Fluoxetine is the best studied drug in pregnant women and the
SSRI with the largest amount of long-term follow-up of exposed infants. Its
long half-life predisposes to accumulation in the neonate, and the rate of
transfer to the baby through breast-feeding is higher than for other SSRIs.
Sertraline. Sertraline has very low serum levels in breast-fed infants and thus
can be a good option for mothers who plan to breast-feed. Sertraline may also
be associated with less fetal medication exposure near delivery (Hendrick et al.
2003).
Paroxetine. Paroxetine is not considered first-line treatment for pregnant
women because of contradictory data regarding cardiac malformations in ex-
posed infants; however, it is generally not recommended that a woman who is
taking paroxetine should switch to an alternative agent (American College of
Obstetricians and Gynecologists Committee on Practice Bulletins—Obstet-
rics 2008).
Citalopram and escitalopram. Studies have generally been positive regard-
ing the safety of citalopram for pregnant women, although one study reported
an increased risk of septal defects (Pedersen et al. 2009), and another found
increased risk of the pooled group of defects consisting of anencephaly, om-
phalocele, and craniosynostosis (Alwan et al. 2007). Minimal data are avail-
able for escitalopram.

Serotonin-Norepinephrine Reuptake Inhibitors

One prospective cohort study found no increased risk of congenital anomalies
following gestational exposure to the serotonin-norepinephrine reuptake in-
hibitor (SNRI) venlafaxine (Einarson et al. 2001).

Mirtazapine
Data on pregnancy outcomes after exposure to mirtazapine are limited. How-
ever, case reports suggest that mirtazapine is effective for treatment-resistant
hyperemesis gravidarum (Guclu et al. 2005; Rohde et al. 2003).
418 Clinical Manual of Psychosomatic Medicine

Bupropion
Bupropion is classified by the U.S. Food and Drug Administration as Cate-
gory B, which indicates no evidence of risk in humans (American College of
Obstetricians and Gynecologists Committee on Practice Bulletins—Obstet-
rics 2008). Bupropion may be especially useful for patients who have not re-
sponded to other medications, who have attentional disorders, or who need
help with smoking cessation.

Tricyclic Antidepressants
Most studies have found that tricyclic antidepressants (TCAs) are not associated
with congenital abnormalities (Simon et al. 2002), and long-term studies have
shown no differences in IQ, language, or temperament between children exposed
to TCAs in utero and nonexposed children (Nulman et al. 2002). Withdrawal
syndromes during the perinatal period have been noted (Altshuler et al. 1996).

Benzodiazepines
A possible association exists between first-trimester exposure to benzodiaz-
epines and the development of cleft lip, cleft palate, and other congenital anom-
alies, although the data have been conflicting, and if an increased risk exists, the
absolute risk is low (Altshuler et al. 1996; Dolovich et al. 1998). Exposure to
benzodiazepines close to the time of labor and delivery has been associated with
transient neonatal intoxication characterized by hypotonia (floppy infant syn-
drome), poor respiratory effort, hypothermia, and feeding difficulties, in ad-
dition to neonatal withdrawal syndromes including restlessness, hypertonia,
hyperreflexia, tremulousness, diarrhea, and vomiting (Altshuler et al. 1996;
McElhatton 1994).

Electroconvulsive Therapy
No randomized controlled trial of electroconvulsive therapy (ECT) during
pregnancy has been conducted. A review of 339 cases found comparable re-
sponse rates between pregnant and nonpregnant women, and the risk of ad-
verse events appears to be low (Anderson and Reti 2009). ECT should be con-
sidered for women with psychotic symptoms, catatonia, or suicidal ideation
(with intent) requiring immediate intervention.
 Obstetrics 419

Treatment of Postpartum Depression

Psychotherapy
Compared with usual postpartum care, psychosocial and psychological inter-
ventions have been shown to reduce depressive symptoms. Interpersonal, psy-
chodynamic, CBT, and group psychotherapy may be effective (Dennis 2005).
The most evidence exists for interpersonal therapy, which has been found to
improve depressive symptoms and social adjustment (O’Hara et al. 2000), as
well as to reduce the likelihood of the development of postpartum depression
(Zlotnick et al. 2006).

Pharmacotherapy
Only a few randomized placebo-controlled treatment studies have been con-
ducted in women with postpartum depression (Appleby et al. 1997; Yonkers
et al. 2008); therefore, antidepressants are used in this population based on
extrapolation of results from studies in the general population. A randomized
trial comparing nortriptyline and sertraline for postpartum depression found
similar efficacy and side-effect burden for these agents (Wisner et al. 2006).

Breast-Feeding and Drugs

Antidepressants and Breast-Feeding
All psychotropic medications are transferred into breast milk and passed on to
the nursing infant. In a pooled analysis of antidepressant drug levels in lactating
mothers, breast milk, and nursing infants, Weissman et al. (2004) found that
nortriptyline, paroxetine, and sertraline usually produce undetectable infant
levels and, therefore, are the preferred choices for breast-feeding women. Flu-
oxetine produced the highest proportion of infant levels. Possible adverse ef-
fects of antidepressants in the infant include irritability, sedation, poor weight
gain, and change in feeding patterns. The benefits of breast-feeding generally
outweigh the relatively low risk of antidepressant medication, but each patient
deserves a careful risk-benefit analysis.
420 Clinical Manual of Psychosomatic Medicine

Benzodiazepines and Breast-Feeding

Benzodiazepines should be used cautiously for treating women who are breast-
feeding. Low dosages and careful monitoring are necessary because sedation
and withdrawal can occur in infants.

Treatment of Bipolar Disorder During Pregnancy

and the Postpartum Period
High Risk for Recurrence
During the immediate postpartum period, women with bipolar disorder have
nearly a sevenfold higher risk of admission for a first episode and a twofold
higher risk for a recurrent episode, compared with nonpregnant and nonpost-
partum women (Yonkers et al. 2004). In a prospective study, the overall risk of
at least one recurrence was 71%. Compared with subjects who continued
mood stabilizer treatment, those who discontinued mood stabilizer treatment
had a twofold higher risk of recurrence, and the time to recurrence was four-
fold shorter (Viguera et al. 2007b).

Mood Stabilizers
Lithium
In a study of women with bipolar disorder treated with lithium, rates of re-
currence during the first 40 weeks after lithium discontinuation were similar
for pregnant and nonpregnant women but then substantially increased post-
partum, although the risk was lower if lithium discontinuation was gradual
(Viguera et al. 2000). Lithium exposure during the first trimester has been as-
sociated with a 20-fold increased risk of developing Ebstein’s anomaly, but the
absolute rate is still low (1/1,000). The most common toxicity effect during
labor is the floppy infant syndrome. During pregnancy, the dosage generally
needs to be titrated upward due to increased renal excretion as pregnancy
progresses. Some researchers recommend decreasing the dosage prior to labor,
due to the rapid reduction in vascular volume during delivery. For mothers
who breast-feed, lithium use has been discouraged, although some evidence
suggests that lithium use in nursing mothers is well tolerated by the infant
(Viguera et al. 2007a).
 Obstetrics 421

Valproate
Valproate is considered a human teratogen because of its association with neu-
ral tube defects, fetal valproate syndrome, and possible long-term adverse
neurocognitive effects. The neural tube defect rate in babies whose mothers
take valproate is about 5%–9%, an effect related to use of the medication 17–
30 days postconception. Folate supplementation has been found to reduce
the risk of neural tube defects. In contrast to the risk to infants exposed to val-
proate during pregnancy, the risk to infants who are breast-fed by mothers
treated with valproate is low (Yonkers et al. 2004).

Carbamazepine
Carbamazepine should generally be avoided during pregnancy due to its as-
sociation with minor and major malformations, including craniofacial defects
and fingernail hypoplasia. Studies have not yet definitively shown whether
carbamazepine is associated with an increased risk of developmental delay or
neural tube defects. Teratogenicity is enhanced when it is coadministered with
another anticonvulsant, particularly valproate. The American Academy of Pe-
diatrics Committee on Drugs (2000) considers carbamazepine to be compat-
ible with breast-feeding.

Lamotrigine
Newport et al. (2008b) reported decreased risk of bipolar disorder recurrence
in pregnant women who took lamotrigine compared with those who discon-
tinued mood stabilizer treatment. Also, lamotrigine’s fetal safety seems to
compare favorably with that of other agents used to manage bipolar disorder,
although more data are needed. The rate of lamotrigine excretion into human
breast milk is similar to that observed with other antiepileptic drugs (Newport
et al. 2008a).

Use of Antipsychotics During Pregnancy

and the Postpartum Period
First-Generation Antipsychotics
Exposure of pregnant women to low-potency antipsychotics for hyperemesis
gravidarum resulted in a 0.4% relative increased risk for congenital anomalies
422 Clinical Manual of Psychosomatic Medicine

associated with first-trimester exposure, but no specific malformation was

identified (Altshuler et al. 1996). A prospective study of haloperidol found no
difference in rates of major malformations between the haloperidol group and
the control group (Diav-Citrin et al. 2005). Infants should be monitored, be-
cause an extrapyramidal syndrome has been observed in babies exposed in
utero to first-generation antipsychotics. Some experts consider the risk asso-
ciated with first-generation antipsychotics to be less than with mood stabiliz-
ers. Limited data on the use of first-generation antipsychotics in women who
breast-feed do not suggest adverse effects (Yonkers et al. 2004).

Second-Generation Antipsychotics
Limited evidence is available to suggest that second-generation antipsychotics
are associated with teratogenesis or neonatal toxicity, although further studies
are needed. One prospective study found no increased risk of birth defects but
a small increased risk for low birth weight (McKenna et al. 2005); in contrast,
another study showed an elevated risk for infants being large for gestational age
(Newham et al. 2008). Very few studies are available regarding the use of anti-
psychotics during breast-feeding. Because psychosis and bipolar disorder usu-
ally require long-term treatment and the data on safety of antipsychotics dur-
ing lactation are limited, the benefits of breast-feeding must be weighed against
the potential risks of medication (Fortinguerra et al. 2009; Gentile 2008).

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 25
Oncology

Depression and Anxiety

A frequent misconception is that depression and anxiety are normal and ex-
pected for patients with cancer; this attitude minimizes the significance of the
patients’ suffering from these psychiatric disorders. Depression and anxiety
are more common in cancer patients than in the general population, and are at
least as prevalent as in other medically ill patients. Depression influences treat-
ment compliance and efficacy, quality of life, functional status, hospital length
of stay, and possibly prognosis and mortality (Miller and Massie 2006; Reich
2008). Effective treatment includes both psychosocial and psychopharmaco-
logical interventions.

Depression
Prevalence
Limitations in research methodology and lack of standardization in diagnostic
criteria contribute to wide variations in prevalence rates of depression in pa-
tients with cancer. Age, gender, type of cancer, treatment, and severity of illness
also influence depression rates. A review of the literature found a mean preva-
lence rate of 25%, with rates ranging from 2%–50% (McDaniel et al. 1995).

427
428 Clinical Manual of Psychosomatic Medicine

Risk Factors for Depression

The following are risk factors for depression in patients with cancer (McDan-
iel et al. 1995; Miller and Massie 2006):

• Poorly controlled pain

• Advanced cancer stage
• Previous history of depression
• Pancreatic, oropharyngeal, and breast cancers
• Poor functional status
• Family history of depression/suicide
• Treatment with medications known to be associated with depression

Diagnostic Considerations
Many symptoms that occur in the context of cancer overlap with the DSM-
IV-TR criteria for major depressive episode (American Psychiatric Association
2000), prompting debate as to whether these shared symptoms should be in-
cluded or excluded when criteria are considered in making a psychiatric diag-
nosis. Anorexia, weight loss, fatigue, sleep disturbance, cognitive impairment,
and psychomotor slowing can each be caused by pathophysiological processes
related to the cancer itself or treatment. An inclusive approach that includes
all symptoms of depression regardless of the possible contributory etiologies is
most often used clinically. For research purposes, the exclusive approach im-
proves specificity by removing fatigue and anorexia from the criteria necessary
for depression, and instead emphasizing depressed mood, anhedonia, and
hopelessness (von Ammon Cavanaugh et al. 2001) (see also Chapter 10,
“Mood Disorders”).

Suicide
Estimates of suicide risk vary, but compared with the general population, can-
cer patients have at least a slightly higher risk for suicide (Hem et al. 2004).
Male patients with cancer of the respiratory tract or prostate cancer have been
shown to have a fourfold increased risk (Hem et al. 2004; Llorente et al. 2005).
Risk factors include uncontrolled pain, advanced disease, fatigue, male gender,
delirium, and hopelessness. Hopelessness is a stronger predictor of suicide than
is depression in patients with advanced terminal cancer (Chochinov et al.
1998).
 Oncology 429

Medical Consequences of Depression

Substantial data have been published regarding the role of psychological factors
or stress in cancer onset, progression, or survival. Due to methodological limi-
tations, publication bias, and confounding factors, the findings are contradic-
tory and inconclusive (Massie and Miller 2011). Studies that support an asso-
ciation between psychological factors and cancer outcomes generally are unable
to demonstrate a clear causal relationship. The data are mixed, but evidence is
available to suggest that depression may be associated with elevated cancer risk,
and stronger evidence suggests that depression affects cancer progression (Spie-
gel and Giese-Davis 2003). Depression may affect the course of the illness due
to the impact on treatment adherence and desire for life-sustaining therapy.
Musselman et al. (2001) reported that 35% of patients with malignant mela-
noma who developed depression during treatment with interferon-α discon-
tinued treatment, compared with 5% who were not depressed.

Pharmacological Treatments for Depression

Few studies have been reported on randomized placebo-controlled trials of
antidepressants in patients with cancer. Selection of an antidepressant often
depends on the side-effect profile and drug-drug interactions.
Selective serotonin reuptake inhibitors. Because of their tolerability, selec-
tive serotonin reuptake inhibitors (SSRIs) are first-line treatment for depres-
sion. SSRIs can cause initial suppression of appetite, but this effect usually
subsides within a few weeks. Serotonin-mediated nausea can occur, especially
at the onset of treatment, but can be reduced with ondansetron. Inhibitors of
cytochrome P450 2D6, such as fluoxetine, paroxetine, bupropion, and dulox-
etine, may prevent conversion of tamoxifen, which is a prodrug, into its active
metabolite, thereby reducing its effectiveness, and therefore these drugs should
be avoided in patients taking tamoxifen (Henry et al. 2008). Fluoxetine has the
longest half-life, which can be advantageous for patients who have periods of
inability to take anything by mouth. Citalopram, sertraline, fluoxetine, and
mirtazapine (a mixed-action antidepressant; see below) have been found effec-
tive for depression induced by interferon-α in patients with cancer or hepatitis
C (Miller and Massie 2006).
Novel and mixed-action antidepressants. Patients with insomnia, anorexia-
cachexia, or nausea may benefit from mirtazapine because of its sedative prop-
430 Clinical Manual of Psychosomatic Medicine

erties, appetite stimulation, and antiemetic effect. Venlafaxine and duloxetine

have been demonstrated to improve neuropathic pain. Bupropion can be stim-
ulating and decrease fatigue, but it usually should be avoided in patients who
are at risk of seizures (Miller and Massie 2006).
Tricyclic antidepressants. The side-effect profile of the tricyclic antidepres-
sants (TCAs) limits their use in patients with cancer, and therefore TCAs
should be considered primarily for patients who have comorbid neuropathic
pain.
Psychostimulants and wakefulness-promoting agents. The rapid onset of
action of the psychostimulants (methylphenidate and dextroamphetamine)
and modafinil can be a significant advantage over antidepressants in some cir-
cumstances, especially for patients with very short life expectancies. Psycho-
stimulants can promote a sense of well-being, increase energy and appetite,
and improve concentration. In patients treated with opioids, psychostimu-
lants may counteract sedation and potentiate the analgesic effects. Side effects
include insomnia, anxiety and agitation, tachycardia, and rarely psychosis.

Psychosocial Interventions for Depression

Various psychotherapeutic interventions are used for cancer patients, includ-
ing psychoeducational, supportive, cognitive-behavioral, existential, psycho-
dynamic, life narrative, dignity-conserving, and meaning-centered therapies.
Psychotherapy may be done individually, in a group setting, or with the pa-
tient’s caregiver (Miller and Massie 2006). The evidence for efficacy of differ-
ent psychosocial interventions has varied widely. The goals of treatment are to
reduce emotional distress, provide education, provide social support, improve
coping, and facilitate resolution of problems. Earlier studies suggested that
group therapy might extend survival in patients with breast cancer (Spiegel et
al. 1989) and malignant melanoma (Fawzy et al. 1993), but subsequent stud-
ies have not substantiated this finding (Ross et al. 2002).

Anxiety
Prevalence
Mixed anxiety and depressive symptoms are generally more prevalent than
anxiety alone in cancer patients. One study showed that nearly one-half of
cancer patients self-reported significant anxiety, but the rate of anxiety disor-
 Oncology 431

ders was 18%, which is similar to the rate in the general population (Stark et
al. 2002).

Diagnostic Considerations
Anxiety is a normal reaction to unpredictability, loss of control, and the threat
of death. Fears related to pain, dependency, disfigurement, and disability may
arise in patients with cancer. Anxiety increases prior to surgical interventions,
during chemotherapy and radiotherapy, and with progression of the illness,
but anxiety may also occur before routine visits even without evidence of can-
cer recurrence. Somatic symptoms, including tachycardia, shortness of breath,
abdominal discomfort, diaphoresis, and feelings of hyperarousal, are common
with anxiety. Patients may experience irritability, insomnia, and poor concen-
tration due to intrusive thoughts related to their prognosis (Miller and Massie
2006). Anxiety disorders need to be recognized not only because of the asso-
ciated psychological distress, but also because anxiety may contribute to non-
compliance with treatment or abrupt discontinuation of treatment.
Phobias. Patients may experience phobias triggered by the medical environ-
ment, such as fear of needles, blood, or hospitals. Patients who are confined to
the hospital may experience agoraphobia, and claustrophobia often occurs in
patients who require magnetic resonance imaging or radiotherapy.
Posttraumatic stress disorder. Patients may develop posttraumatic stress
disorder (PTSD) after completion of cancer treatment. Younger age, lower in-
come, less education, advanced disease, and longer hospitalizations are asso-
ciated with increased PTSD symptoms (Cordova et al. 1995; Jacobsen et al.
1998).
Misdiagnosis of anxiety as primary psychiatric disorder. Anxiety can be
misdiagnosed as a primary psychiatric disorder when it is a side effect of med-
ication or is secondary to medical causes such as dyspnea or uncontrolled
pain. Restlessness may be caused by corticosteroids, stimulants, or antiemetic
dopamine-blocking agents (due to akathisia) (Massie and Miller 2011). Med-
ical causes of anxiety in cancer patients are listed in Table 25–1.

Treatment of Anxiety
Psychological interventions, including cognitive-behavioral therapy, relaxation
techniques, psychoeducation, and supportive therapy, have demonstrated effi-
432 Clinical Manual of Psychosomatic Medicine

Table 25–1. Medical causes of anxiety in cancer patients

Uncontrolled pain
Corticosteroids
Dopamine-blocking antiemetics (e.g., metoclopramide, prochlorperazine)
Opioid or benzodiazepine withdrawal
Chemotherapy and radiotherapy
Dyspnea
Metabolic abnormalities
Hypoglycemia
Encephalopathy

cacy in the short-term treatment of mild to moderate anxiety (Jacobsen and

Jim 2008). Pharmacological treatment may be necessary to alleviate severe anx-
iety, and benzodiazepines are often the first-line treatment. Alprazolam and lo-
razepam reduce anticipatory nausea and vomiting, as well as postchemother-
apy nausea and vomiting (Greenberg et al. 1987). Elderly patients in particular
need to be monitored for somnolence and mental status changes when treated
with a benzodiazepine. Low-dose antipsychotics should be considered for pa-
tients who are both confused and anxious. For patients who have significant
respiratory compromise, a low-dose antihistamine (e.g., hydroxyzine) or an
antipsychotic may be effective. If anxiety develops in the setting of a preexisting
anxiety disorder or panic disorder, treatment with an SSRI is indicated.

Mania
Corticosteroids are the most frequent cause of mania in cancer patients. If
high-dose corticosteroids are planned as part of a chemotherapy regimen, sub-
sequent cycles may be preceded by initiation of valproate or lithium (in the
absence of contraindications) to avert recurrent episodes of mania. Mania
with psychotic features may be confused with delirium. Interferon-α-2b has
also been reported to induce mania or mixed states (Greenberg et al. 2000).
 Oncology 433

Pain
Pain is most often caused by direct effects of the tumor or complications of
treatment, but unrelated sources of pain also need to be considered. Compared
to cancer patients without pain, cancer patients with pain have lower levels of
functioning, increased depressive symptoms, and decreased quality of life (Ta-
voli et al. 2008). Uncontrolled pain, adverse effects of opioids, and fear of pain
contribute to depressive symptoms. Depressive symptoms that develop in the
setting of poorly controlled pain should not be assumed to represent an auton-
omous depression unless the symptoms persist despite adequate pain relief.
One review found a prevalence of both pain and depression of 35%, and pain
intensity was shown to positively correlate with depression. Although the evi-
dence suggests an association between pain and depression, insufficient data
are available to support a causal relationship (Laird et al. 2009).

Management
Effective treatment frequently involves a multidisciplinary approach, which
may include oncology, anesthesia, psychiatry, psychology, physical therapy,
pharmacy, and nursing. Pharmacotherapy is the mainstay of treatment and
should be individualized to the patient. The risk of addiction in patients who
receive opioids for cancer pain is minimal and should rarely limit treatment.

Cancer-Related Fatigue
Cancer-related fatigue is reported as the most frequent and disabling symp-
tom in 60%–90% of patients with advanced cancer. The prevalence of fatigue
among patients receiving chemotherapy is greater than 60%. Factors identi-
fied as contributing to cancer fatigue include pain, emotional distress, insom-
nia, anemia, and hypothyroidism (Mock et al. 2000), as well as chemotherapy,
radiation therapy, and other medications (e.g., opioids, sedatives) (Table 25–
2). Much cancer fatigue, however, does not have an apparent cause; the un-
derlying mechanism has not been clearly identified but may include abnormal
inflammatory response and cytokine release or disruption of the hypotha-
lamic-pituitary-adrenal axis (Minton et al. 2008).
434 Clinical Manual of Psychosomatic Medicine

Table 25–2. Causes of cancer-related fatigue

Cancer treatment
Interferon
Chemotherapy
Irradiation
Pain
Anemia
Nutritional deficits
Hormone imbalance
Thyroid
Estrogen
Androgens
Immune response
Cytokine release
Drug effects
Opioids
Sedatives
Psychiatric disorders
Sleep disruption
Depression
Source. Reprinted from Massie MJ, Miller K: “Oncology,” in The American Psychiatric Publish-
ing Textbook of Psychosomatic Medicine, 2nd Edition. Edited by Levenson JL. Washington, DC,
American Psychiatric Publishing, 2011, p. 532. Used with permission.

Management
Some evidence suggests that methylphenidate improves fatigue (Bruera et al.
2003). Stronger support exists for treatment with hematopoietic agents to re-
lieve fatigue associated with chemotherapy-induced anemia. Antidepressants
are not indicated because cancer-related fatigue and depression are different
entities (Minton et al. 2008).
 Oncology 435

Delirium
Delirium occurs in 15%–40% of hospitalized cancer patients and is associated
with a 30-day mortality rate of 25%. In a study of patients with non–central
nervous system cancers, 35% had a single cause of delirium identified and
65% had multiple etiologies. The most common causes were medications
(usually opioids) and metabolic abnormalities. Delirium improved in 65% of
the patients, although it was a poor overall prognostic factor (Tuma and
DeAngelis 2000). Antineoplastic and immunotherapeutic agents can cause al-
tered mental status and delirium (Massie and Miller 2011) (Table 25–3).

Cancer-Related Anorexia-Cachexia Syndrome

Cancer-related anorexia-cachexia syndrome (CACS) is a hypercatabolic state
associated with poor appetite and reduced body weight due to loss of muscle
mass and adipose tissue. Many agents have been evaluated for the treatment of
CACS, but only corticosteroids and progestational agents (e.g., megestrol ac-
etate) have proven benefit (Yavuzsen et al. 2005).

Treatment of Hot Flashes

Vasomotor symptoms can be caused by surgically induced menopause, prema-
ture cessation of ovarian function caused by chemotherapy, or the use of adju-
vant hormone therapy (e.g., tamoxifen, anastrozole). Hot flashes in women
with breast cancer are difficult to treat because estrogen therapy is contraindi-
cated and because some SSRIs (e.g., paroxetine and fluoxetine) interfere with
tamoxifen metabolism. SSRIs, serotonin-norepinephrine reuptake inhibitors
(SNRIs), clonidine, gabapentin, and megestrol effectively reduce hot flashes
(Loprinzi et al. 2007; Nelson et al. 2006).

End-of-Life Care
The dying patient is often comfortable talking about death, but family mem-
bers and sometimes the hospital staff may be reluctant to engage in such con-
versations. A minority of patients with advanced cancer have end-of-life
436 Clinical Manual of Psychosomatic Medicine

Table 25–3. Neuropsychiatric side effects of common

chemotherapeutic agents
Agent Side effects

Hormones
Corticosteroids Mild to severe insomnia, hyperactivity, anxiety, depression,
psychosis with prominent manic features
Tamoxifen Sleep disorder, irritability
Biologicals
Cytokines Encephalopathy
Interferon Depression, suicidality, mania, psychosis, delirium, akathisia, seizures
Interleukin-2 Dysphoria, delirium, psychosis, seizures
Chemotherapy agents
L-Asparaginase Somnolence, lethargy, delirium, depression
Chlorambucil Hallucinations, lethargy, seizures, stupor, coma
Capecitabine Multifocal leukoencephalopathy, cerebellar ataxia, reversible
neuromuscular syndrome: trismus, slurred speech, confusion,
ocular abnormalities
Cisplatin Encephalopathy (rare), sensory neuropathy
Cytarabine Delirium, seizures, leukoencephalopathy
5-Fluorouracil Fatigue, rare seizures or confusion, cerebellar syndrome
Gemcitabine Fatigue
Ifosfamide Lethargy, seizures, drunkenness, cerebellar signs, delirium,
hallucinations
Methotrexate Intrathecal regimens: possible leukoencephalopathy (acute and
delayed forms)
High dose: possible transient delirium
Procarbazine Somnolence, depression, delirium, psychosis, cerebellar disorder
Taxanes Sensory neuropathy, fatigue, depression
Thalidomide Fatigue, reversible dementia
Vincristine, Depression, fatigue, encephalopathy
vinblastine,
vinorelbine
 Oncology 437

Table 25–3. Neuropsychiatric side effects of common

chemotherapeutic agents (continued)
Agent Side effects

Multikinase inhibitors
Sorafenib, Posterior leukoencephalopathy syndrome
sunitinib,
bevacizumab
Source. Reprinted from Massie MJ, Miller K: “Oncology,” in The American Psychiatric Publish-
ing Textbook of Psychosomatic Medicine, 2nd Edition. Edited by Levenson JL. Washington DC,
American Psychiatric Publishing, 2011, p. 531. Copyright 2011, American Psychiatric Associa-
tion. Used with permission.

discussions with their physicians. Such exchanges are associated with less ag-
gressive medical care near death; more aggressive care is associated with de-
creased quality of life and a higher risk of major depressive disorder in bereaved
caregivers (Wright et al. 2008).

References
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disor-
ders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Associ-
ation, 2000
Bruera E, Driver L, Barnes EA, et al: Patient-controlled methylphenidate for the man-
agement of fatigue in patients with advanced cancer: a preliminary report. J Clin
Oncol 21:4439–4443, 2003
Chochinov HM, Wilson KG, Enns M, et al: Depression, hopelessness, and suicidal
ideation in the terminally ill. Psychosomatics 39:366–370, 1998
Cordova MJ, Andrykowski MA, Kenady DE, et al: Frequency and correlates of post-
traumatic-stress-disorder–like symptoms after treatment for breast cancer. J Con-
sult Clin Psychol 63:981–986, 1995
Fawzy FI, Fawzy NW, Hyun CS, et al: Malignant melanoma: effects of an early struc-
tured psychiatric intervention, coping, and affective state on recurrence and sur-
vival 6 years later. Arch Gen Psychiatry 50:681–689, 1993
Greenberg DB, Surman OS, Clarke J, et al: Alprazolam for phobic nausea and vom-
iting related to cancer chemotherapy. Cancer Treat Rep 71:549–550, 1987
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Greenberg DB, Jonasch E, Gadd MA, et al: Adjuvant therapy of melanoma with inter-
feron-alpha-2b is associated with mania and bipolar syndromes. Cancer 89:356–
362, 2000
Hem E, Loge JH, Haldorsen T, et al: Suicide risk in cancer patients from 1960 to 1999.
J Clin Oncol 22:4209–4216, 2004
Henry NL, Stearns V, Flockhart DA, et al: Drug interactions and pharmacogenomics
in the treatment of breast cancer and depression. Am J Psychiatry 165:1251–
1255, 2008
Jacobsen PB, Jim HS: Psychosocial interventions for anxiety and depression in adult
cancer patients: achievements and challenges. CA Cancer J Clin 58:214–230,
2008
Jacobsen PB, Widows MR, Hann DM, et al: Posttraumatic stress disorder symptoms
after bone marrow transplantation for breast cancer. Psychosom Med 60:366–
371, 1998
Laird BJ, Boyd AC, Colvin LA, et al: Are cancer pain and depression interdependent?
A systematic review. Psychooncology 18:459–464, 2009
Llorente MD, Burke M, Gregory GR, et al: Prostate cancer: a significant risk factor for
late-life suicide. Am J Geriatr Psychiatry 13:195–201, 2005
Loprinzi CL, Kugler JW, Barton DL, et al: Phase III trial of gabapentin alone or in con-
junction with an antidepressant in the management of hot flashes in women who
have inadequate control with an antidepressant alone: NCCTG N03C5. J Clin
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Massie MJ, Miller K: Oncology, in The American Psychiatric Publishing Textbook of
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diagnosis, biology, and treatment. Arch Gen Psychiatry 52:89–99, 1995
Miller K, Massie MJ: Depression and anxiety. Cancer J 12:388–397, 2006
Minton O, Richardson A, Sharpe M, et al: A systematic review and meta-analysis of
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100:1155–1166, 2008
Mock V, Atkinson A, Barsevick A, et al: NCCN practice guidelines for cancer-related
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pression induced by high-dose interferon alfa. N Engl J Med 344:961–966, 2001
Nelson HD, Vesco KK, Haney E, et al: Nonhormonal therapies for menopausal hot
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Ross L, Boesen EH, Dalton SO, et al: Mind and cancer: does psychosocial intervention
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 26
Pulmonary Disease

Very few experiences command the personal attention demanded by hunger

for air. Whether diminished oxygenation occurs suddenly as with an asth-
matic attack or insidiously as with chronic obstructive pulmonary disease
(COPD), it may compromise cognition, kindle anxiety, threaten content-
ment, and intrude upon an individual’s life with suffocating insistence. Lung
disease is common. Psychiatric morbidity may aggravate or be exacerbated by
pulmonary problems and the management strategies designed to relieve those
problems, whether pharmacological or procedural. In turn, psychiatric med-
ication may ease suffering but impede recovery if not used wisely.

Common Pulmonary Conditions

Chronic Obstructive Pulmonary Disease
COPD is widespread, costly, and deadly. The worldwide prevalence ranges
from 10% to 23% in men, and half that in women. The direct and indirect
costs in the United States for each person with COPD exceed $3,000 annu-
ally. COPD is presently the fourth leading cause of death in the world but is
projected to be the third by 2020 (Putman-Casdorph and McCrone 2009).

441
442 Clinical Manual of Psychosomatic Medicine

Anxiety Disorders
Anxiety disorders, particularly generalized anxiety disorder and panic disor-
der, not only are much more prevalent in patients with COPD than in the
general population, but also are associated with increased mortality and de-
creased functional status and quality of life (Brenes 2003; Putman-Casdorph
and McCrone 2009). Posttraumatic stress disorder was identified in 25%–
45% of patients who required mechanical ventilation in the course of critical
illness, including acute lung injury and acute respiratory distress syndrome
(Davydow et al. 2008; Shanmugam et al. 2007). Other sources of anxiety
symptoms include nicotine withdrawal and some bronchodilators.
Pharmacological management. Low dosages of a short-acting benzodiaz-
epine, such as lorazepam, may be judiciously used if carefully monitored,
especially in patients prone to carbon dioxide (CO2) retention. Large, suffi-
ciently powered trials of selective serotonin reuptake inhibitors, tricyclic anti-
depressants, and buspirone in patients with COPD have not been reported,
but small studies suggest that these agents are effective and reasonably toler-
ated, although onset to benefit may require weeks (Jain and Lolak 2009; Sha-
piro et al. 2011). Short-term relief for individuals who cannot safely tolerate
benzodiazepines may be achieved with off-label use of gabapentin, hydrox-
yzine, pregabalin, or some antipsychotics. Nicotine replacement will relieve the
acute withdrawal anxiety that these patients experience when hospitalized.
Psychotherapy and other strategies. Biofeedback, cognitive-behavioral
therapy (CBT), progressive relaxation, and pulmonary rehabilitation are some-
times helpful for anxiety disorders in patients with COPD, although results
vary. These approaches have the advantage of not requiring patient adherence
to a psychotropic medication regimen in a population that often already feels
burdened by pharmacology and is prone to poor medication compliance
(Maurer et al. 2008).

Depression
Depression is common among patients with COPD. Although prevalence
rates vary from 20% to 70% in various studies (Maurer et al. 2008; Solano et
al. 2006), patients with stable COPD have the lowest rates, followed by those
who recently recovered from an acute exacerbation, followed by those with
ongoing severe disease (Jain and Lolak 2009).
 Pulmonary Disease 443

Management. Management strategies, including antidepressants, CBT,

pulmonary rehabilitation, and electroconvulsive therapy have all been used
safely and effectively for depression in patients with COPD, although out-
come data are less plentiful for depression than for anxiety disorders (Putman-
Casdorph and McCrone 2009; Schak et al. 2008). Patients who smoke and
hope to stop may benefit from selection of bupropion as an antidepressant.

Asthma
Asthma afflicted about 24.5 million Americans in 2009 (American Lung Asso-
ciation 2011). Age-adjusted mortality rates rise in socioeconomically disadvan-
taged groups. Although asthma was once construed as a truly psychosomatic ill-
ness with psychological causation, current research focuses instead on the
complex interrelationship between asthma and psychological factors because
this web can complicate both accurate diagnosis and effective management.
Anxiety Disorders
Anxiety disorders, particularly panic disorder and posttraumatic stress disor-
der, are nearly twice as common in patients with asthma as in those without
(Jain and Lolak 2009; Roy-Byrne et al. 2008). Cause and effect may be inter-
dependent: evidence suggests that poor mental health and increased stress can
contribute to airway instability, whereas some asthma medications increase
anxiety (Jain and Lolak 2009).
Psychopharmacological management. Psychopharmacological manage-
ment of anxiety disorders in patients with asthma is the same as for other pa-
tients with anxiety disorders, although benzodiazepines should be used
cautiously in individuals with a known propensity for CO2 retention.
Psychotherapy and other strategies. Although results are encouraging,
psychological interventions such as biofeedback, relaxation therapy, and CBT
have not been sufficiently studied in patients with asthma to affirm definitive
effectiveness (Yorke et al. 2007).
Depression
In older adults with asthma, depression occurs more commonly than anxiety
disorders and is associated with increased use of health care resources and in-
creased likelihood of medical hospitalization within the subsequent year (Jain
and Lolak 2009).
444 Clinical Manual of Psychosomatic Medicine

Management. Management strategies, whether pharmacological or psy-

chological, should be chosen with particular attention to the patient’s invest-
ment in treatment, because depressed mood contributes to less commitment
to self-care and adherence to the treatment plan.

Ventilator Dependence
As the population has aged, the medical comorbidity in patients undergoing
major surgical interventions has increased; infections and other postoperative
complications increase the duration of ventilator dependence. The psychiatrist
is often consulted when the patient does not make the desired progress toward
ventilator independence. Delirium, anxiety, and depression may all compro-
mise or delay successful ventilator weaning (Shapiro et al. 2011). Anger, frus-
tration, loneliness, and discouragement are commonly experienced by individ-
uals obliged to remain on a ventilator (Castillo and Egan 1974; Pattison and
Watson 2009).

Delirium
Delirium in ventilator-dependent patients may be particularly aggravated by
hypoxia, pain, analgesics, sedatives, and sleep deprivation; other common pre-
cipitants of delirium, such as infection and metabolic derangements, are also
frequent.
Management. Management may sometimes require thorough sedation
with propofol or dexmedetomidine until other physiological and metabolic
aberrations are addressed. However, continuous sedation by infusion is asso-
ciated with increased duration of mechanical ventilation, longer hospital
lengths of stay, and increased rates of organ failure (Brush and Kress 2009).
Reversing the delirium, when possible, is imperative to clear the path for an
accurate assessment of anxiety or depression and to enable the patient to col-
laborate constructively in the ventilator weaning process.

Anxiety
Anxiety may be fueled in ventilator-dependent patients by inability to talk; loss
of independence; immersion in a tangle of tubes and insistent alarms; exces-
sively rapid taper of sedatives; inability to move, cough, or use the toilet; fear of
the uncertain future; and the presence of gowned and masked staff and visitors.
 Pulmonary Disease 445

Management. Management of anxiety in ventilator-dependent patients

may include judicious use of benzodiazepines. Other agents with less poten-
tial for a direct effect on respiratory function include antipsychotics, such as
haloperidol (with the added advantage of its ability to be given intravenously);
the anxiolytic hydroxyzine (except when anticholinergic effects may outweigh
the benefit); and possibly the anticonvulsant gabapentin. Equally important,
by encouraging the patient to make persistent attempts at communication
(e.g., lip articulation or writing), explaining to the patient the surroundings
and meaning of the various alarms and functions of the different teams, and
consistently coaching the patient in weaning strategies, health care providers
better enable the patient to recapture some sense of understanding and par-
ticipation, if not control.

Depression
A ventilator-dependent patient may develop depression or demoralization
when faced with an unexpectedly prolonged intensive care stay, feelings that
one’s family is being unduly burdened, loss of autonomy and independent
identity, ambivalence about consenting for the procedure, uncertain progno-
sis, and lack of connection with and trust of a staff that changes with each
shift.

Management. Management of depression in a ventilator-dependent patient

requires consideration of the typically long latency of response to conven-
tional antidepressant agents. A small case report literature exists on the use of
stimulants such as methylphenidate to alleviate depression more quickly and
thereby allow the patient to engage in weaning and pulmonary rehabilitation
sooner than would otherwise have been possible (Rothenhausler et al. 2000).

Restrictive Lung Diseases

Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis is the most common of the interstitial lung dis-
eases. It primarily affects adults older than 40 years. No cure is available; im-
munosuppressive medications are used to suppress disease activity. Progressive
dyspnea increases anxiety, and depression is estimated to occur in 25% of pa-
tients (Shanmugam et al. 2007).
446 Clinical Manual of Psychosomatic Medicine

Sarcoidosis
Sarcoidosis can affect multiple organ systems, but the lungs are a primary tar-
get. Of these patients, 5%–10% will have central nervous system involvement
and may present with depression, psychosis, or cognitive decline. Depression
occurs twice as frequently in patients with pulmonary sarcoidosis as in the
general population; women experience a higher likelihood than men (Shan-
mugam et al. 2007). Stress has been associated with increased disease activity
and progression; quality of life deteriorates with the diagnosis of sarcoidosis
(Jain and Lolak 2009).

Pulmonary Hypertension
Pulmonary hypertension is a chronic disease of progressively increasing pulmo-
nary arterial pressure that develops insidiously, often escaping detection for years
after the first symptoms occur. Over the past 10 years, inhaled and oral prosta-
cyclins (e.g., iloprost and sildenafil, respectively) and endothelin-antagonist
drugs (e.g., bosentan) have improved mean survival from 2 years to 6–7 years.
However, these agents are expensive ($18,000–$36,000 annually), and the im-
proved exercise capacity has not yet been shown to translate into improved qual-
ity of life or other dimensions of mental health (Wryobeck et al. 2007).

Psychiatric Issues
Psychiatric issues for patients with pulmonary hypertension include panic dis-
order, present in 20% of patients, and depression, diagnosed in 10% (Shafa-
zand et al. 2004). Additionally, patients with pulmonary hypertension expe-
rience significant reductions in their functional capacity but do not appear ill
to family and friends, a fact that increases their social isolation and further im-
pairs their ability to adapt to a foreshortened future and constricted role in
life.

End-of-Life Issues
Palliative care deserves discussion among patients with pulmonary hyperten-
sion, but timing is difficult. In one study of 132 patients who received at-
tempted cardiopulmonary resuscitation, it was unsuccessful in 80%, and only
8% survived beyond 1 week (Hoeper et al. 2002). Cessation of prostacyclins,
particularly when administered intravenously, can precipitate death within
 Pulmonary Disease 447

hours or less; this has been likened to a decision to remove a conscious patient
from ventilator support (Wryobeck et al. 2007), imposing a weighty decision
on the patient and family.

Hyperventilation Syndrome
Hyperventilation syndrome (HVS) may occur in 10% of the population, al-
though females in their 30s and 40s are at highest risk. An increased rate of
breathing is easy to spot, but respiratory alkalosis and its sequelae of dizziness
and paresthesias may also result from a less obvious increase in the depth of
breathing. Although benign and usually self-limited to minutes (but occasion-
ally hours), HVS needs to be distinguished from medical causes of hyperventi-
lation (e.g., pulmonary embolus, coronary insufficiency, diabetic ketoacidosis,
salicylate ingestion, asthma, carbon monoxide poisoning) to ensure appropriate
intervention. The majority of patients with HVS episodes recover spontane-
ously; others find beta-blockers, sedatives, or the bag rebreathing method help-
ful (Coffman and Levenson 2011; Shanmugam et al. 2007).

Tuberculosis
Tuberculosis had been steadily waning in the latter half of the twentieth cen-
tury following the discovery in 1951 that isoniazid was an effective antituber-
cular agent. However, with the advent of AIDS, increasing substance abuse,
and the emergence of drug-resistant strains, the incidence of tuberculosis is
now increasing once again. Individuals who abuse alcohol and other sub-
stances are at increased risk of acquiring tuberculosis. Alcohol dependence
and a history of mental illness also increase the risk of mania or psychosis with
isoniazid therapy (Coffman and Levenson 2011).

Psychiatric Symptoms Associated

With Pulmonary Medications
Systemic Corticosteroids
Systemic corticosteroids, especially when administered in higher dosages (e.g.,
prednisone 80 mg/day or more), are well known to induce emotional lability,
acute dysphoria, mania, cognitive dysfunction, and even psychosis.
448 Clinical Manual of Psychosomatic Medicine

Management
Management by steroid dosage reduction or by addition of antipsychotics, ben-
zodiazepines, anticonvulsants, or lithium has been effective, although anticon-
vulsant or lithium augmentation requires more time and is therefore more
practical when sustained use of steroids is anticipated (Shanmugam et al. 2007).

Theophylline
Theophylline, although not commonly used in the hospital, may increase
restlessness and anxiety, lower the seizure threshold, and increase lithium
clearance by 20%–30% (Coffman and Levenson 2011).

Inhaled Bronchodilators and Anticholinergics

Inhaled bronchodilators and anticholinergics do not appear to have signifi-
cant psychiatric side effects (Shanmugam et al. 2007).

Rifampin
Rifampin, used in tuberculosis treatment, affects multiple cytochrome P450
isoenzymes; through 3A4 induction, rifampin can decrease effective levels of
diazepam, valproic acid, and tricyclic antidepressants (Coffman and Levenson
2011).

References
American Lung Association: Trends in Asthma Morbidity and Mortality. July 2011.
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 27
Rehabilitation Medicine

Rehabilitation medicine is a diverse specialty: patients are young and old,

abruptly deprived of health or debilitated by inexorable senescence, whole in
body but not mind, or perhaps fully cognizant but unable to move. Regardless
of whether the issue at hand is acute or chronic, restoration of function to
whatever degree possible invariably requires the attention and effort of a mul-
tidisciplinary team. Such teams are often well integrated and frequently in-
clude a psychologist who provides a wide range of vital services to the patient
and family. Consequently, a request for psychiatric consultation often arises
well into the course of the patient’s rehabilitative work, after other strategies
have fallen short. The prudent psychiatrist remembers that he or she is joining
an existing team and, in developing an understanding of the patient, will har-
vest history and observations from the full spectrum of caregivers, some of
whom spend extended daily time with the patient. Although the range of
problems encountered in rehabilitation medicine is broad, only three of the
more common difficulties that prompt psychiatric evaluation are discussed in
this chapter: traumatic brain injury (TBI), stroke, and spinal cord injury.

Traumatic Brain Injury

TBI is common, costly, and consequential (Fann et al. 2011; Rao and Lyket-
sos 2002). Of the 2 million Americans who incur a TBI each year, 25% are

451
452 Clinical Manual of Psychosomatic Medicine

hospitalized. Although improved acute care has dramatically reduced mortal-

ity, it has thereby increased morbidity and long-term disability. The incidence
of TBI is bimodal: vehicular accidents, violence, sports, and workplace injury
cause a peak incidence in young adults ages 15–24 years, and falls account for
a second peak in the over-60 population. Alcohol is associated with half of all
cases. The sequelae of TBI are substantial: 25% of those who sustain an injury
are unable to return to work in the year following the event, and many of these
individuals require occupational, speech, and physical therapy to recapture a
measure of independent function. Cognitive and behavioral difficulties range
from mild to severe and frequently do not correlate with overt signs of injury,
adding complexity to the individual’s efforts to reengage society.

Primary Brain Injury

Primary brain injury includes both focal and diffuse damage due to mechan-
ical forces at the time of the trauma.

Focal Injury
Focal injury is typically caused by a direct blow to the head. The internal ar-
chitecture of the skull, with bony ridges cradling the inferior aspect of the
frontal and temporal lobes, renders these locations especially susceptible to
coup-contrecoup injuries.
Cerebral contusion. Cerebral contusion commonly results in a loss of con-
sciousness. Although recovery is the rule, focal neurological signs and symp-
toms such as headache, altered coordination and balance, disorientation,
confusion, and seizures may persist for several weeks. Generally, structural
damage is not evident on imaging studies, although postinjury edema may oc-
cur (Simon et al. 1999).
Subdural hematoma. Subdural hematoma is caused by venous shearing in
the space between the dura mater lining the interior of the skull and the arach-
noid mater that wraps the cortex. Acute subdural hematomas often result from
extreme acceleration or deceleration injuries and, without rapid surgical de-
compression, result in a mortality rate approaching 75%. In contrast, chronic
subdural hematomas may develop over weeks and remain largely asympto-
matic (Marik et al. 2002).
 Rehabilitation Medicine 453

Epidural hematoma. Epidural hematoma is usually associated with a lateral

skull fracture, rupture of the middle meningeal artery or vein, and temporal or
temporoparietal injury. Initial loss of consciousness may be followed by a de-
ceptive return of lucidity before neurological decline begins to accelerate; ur-
gent surgical evacuation of the clot is imperative (Marik et al. 2002).

Diffuse Axonal Injury

Diffuse axonal injury is more commonly the result of rotational forces or
rapid changes in velocity rather than direct trauma. Computed tomography is
commonly unrevealing; diffusion-weighted magnetic resonance imaging may
disclose axonal edema, but this edema is not typically immediately evident.
Normal results from head imaging followed by changes in cognition and con-
sciousness should alert the physician to diffuse injury (Lezak 1995).

Secondary Brain Injury

Secondary brain injury is the result of a cascade of physiological changes that
develop in the wake of trauma and often in concert with the more gradual de-
velopment of swelling that introduces increased pressure and structural chal-
lenge within the fixed boundaries of the skull.

Prognostic Factors
The following premorbid factors are associated with less favorable outcomes
for patients with TBI (Silver et al. 2002):

• Comorbid substance abuse disorder

• Older age
• Lower IQ
• History of prior brain injury

The following posttraumatic factors are associated with less favorable out-
comes:

• Loss of consciousness greater than 5 minutes

• Amnesia greater than 12 hours
• New onset or exacerbation of preexisting seizures
454 Clinical Manual of Psychosomatic Medicine

Clinical Disorders and Syndromes

Personality Patterns and Associated Behaviors
Personality patterns and associated behaviors change in 25% of individuals
with TBI; changes may include aggression, apathy, disinhibition, labile affect,
and poor social manners. These patients may be uncharacteristically careless,
irritable, oblivious, suspicious, and unkempt (Koponen et al. 2002).

Cognitive Dysfunction
After TBI, patients may experience memory, language, and executive function
disorders. Retraining can, over time, ease but not erase the net debilitation.
Neuropsychological testing is essential to adequately assess executive deficits
and design a focused rehabilitation program.

Chronic Pain
Chronic pain is an underdiagnosed result of TBI; the incidence is independent of
posttraumatic stress disorder (PTSD) and depression (Nampiaparampil 2008).

Mood Disorders
Mood disorders occur in 25% of individuals following a mild TBI, and higher
rates occur in those with more severe injuries. Prior substance abuse or mood
disorder, less education, and erratic employment history presage a higher inci-
dence of depression (Dikman et al. 2004). In one study of more than 500 adults
with TBI, less than half who met criteria for major depression received antide-
pressants or counseling; the occurrence of major depression was an independent
predictor of poorer quality of life 1 year after injury (Bombardier et al. 2010).
Pseudobulbar affect is discussed later in this chapter in the section on stroke.

Anxiety Disorders
Anxiety disorders, most commonly generalized anxiety disorder and PTSD,
may also develop after TBI.

Substance Abuse or Dependence

Substance abuse or dependence is a substantial risk factor for patients with
TBI. In multiple studies, “at-risk” alcohol drinking patterns were present in
more than 50% of patients, and toxicology evidence of illicit substance use
was present in more than one-third of patients. Although substance abuse
 Rehabilitation Medicine 455

rates decline following TBI, problematic use persists and complicates the mul-
tiple challenges faced by patients with TBI (Graham and Cardon 2008).

War-Related Traumatic Brain Injury

War-related TBI has become an increasing medical concern. In one survey of
2,525 U.S. Army infantry soldiers approximately 3 months after a year-long
deployment in Iraq, 5% reported injuries resulting in loss of consciousness,
and 10% reported injuries with altered mental status. Of those who lost con-
sciousness, 45% met criteria for PTSD, compared with 25% of those who ex-
perienced altered mental status, 15% of the soldiers with non-TBI injuries,
and 10% of those who were uninjured (Hoge et al. 2008). The contextual fac-
tors of combat-related injury (e.g., less likely role of substance use as a caus-
ative factor, injury’s occurrence during service to country, occupational con-
sequences of injury) may influence the psychiatric aftermath in comparison
with civilian injury, but data are not yet available.
Neuropsychiatric sequelae of war-related TBIs have been grouped as fol-
lows (Halbauer et al. 2009):

• Cognitive dysfunctions, including difficulties in memory, attention, and

language
• Neurobehavioral disorders, such as depression, PTSD, and sleep problems
• Somatosensory disruptions, frequently caused by trauma to sensory organs
• Somatic symptoms, primarily headache and chronic pain
• Substance dependence

Treatment and Management

Treatment and management of the consequences of TBI are best addressed by
an integrated and multidisciplinary effort. The disruptions experienced by pa-
tients with TBI are often complex, crossing multiple domains and extending
beyond the injured person.

Coordinated Rehabilitation
When possible, coordinated rehabilitation, with contributions from social
work, occupational therapy, psychology, and psychiatry, will enable the patient
to maximize his or her potential. The following components may be helpful:
456 Clinical Manual of Psychosomatic Medicine

• Cognitive rehabilitation
• Stress management
• Creating structure and developing routine
• Family education

Pharmacotherapy
Pharmacotherapy is an important adjunct for patients with Axis I disorders,
severe behavioral disturbances, or both. The injured brain is often more sen-
sitive and may require longer to respond fully, underscoring the importance of
beginning with a low dose, advancing slowly, and coaching patience and per-
sistence to individuals who often find such qualities in short supply.

Antidepressants. Selective serotonin reuptake inhibitors (SSRIs) improve

mood and diminish aggression (Perino et al. 2001). Careful consideration
should be given before using bupropion, which lowers seizure threshold, or
tricyclic antidepressants (TCAs), which increase sensitivity to side effects, in-
cluding orthostasis and anticholinergic aggravation of cognitive dysfunction.

Stimulants. Dopamine agonists have been used to target post-TBI apathy

and fatigue. Methylphenidate has demonstrated improved mental processing
speed and reduced intensive care unit and hospital length of stay after acute
TBI, but neither of these benefits was correlated with methylphenidate’s effect
on depression (Moein et al. 2006; Whyte et al. 1997). Amantadine has also
demonstrated improved cognition and executive function in patients with
TBI (Kraus et al. 2005; Sawyer et al. 2008).

Anticonvulsants. Anticonvulsants stabilize mania. Lithium use is not rec-

ommended due to increased adverse effects and possible neurotoxicity.

Antipsychotics. Antipsychotics may calm agitation (Kim and Bijlani 2006),

but psychiatrists should consider avoiding high-potency, strongly anticholin-
ergic, and seizure threshold–lowering antipsychotics. Patients with TBI are
more sensitive to extrapyramidal side effects.

Benzodiazepines. Benzodiazepines may calm and relieve anxiety, but in

TBI patients, they have narrower therapeutic index free of cognitive and mo-
tor compromise compared with their use in non-TBI patients.
 Rehabilitation Medicine 457

Stroke
About 800,000 Americans annually have strokes, and about half of these in-
dividuals develop neuropsychiatric aftereffects (Carson et al. 2011). Eight-five
percent of strokes are ischemic, and three-quarters of individuals survive the
first year following ischemic strokes. The remaining 15% of strokes are hem-
orrhagic, and only one-third of individuals with hemorrhagic strokes survive
the first year. The prevalence of stroke survivors in America is about 3 million.
Stroke is the most common cause of disability and the third most common
cause of death in the United States.

Stroke Sequelae
Stroke sequelae may include alterations in mental status, cognition, and be-
havior.

Delirium
Delirium affects one-third of patients in the days immediately following a
stroke and is associated with a longer length of hospitalization and increased
risk of subsequent dementia (Henon et al. 1999).

Depression
Depression occurs in one-third of stroke patients, with a peak incidence 6–
24 months poststroke (Hackett et al. 2005). Probability is increased for pa-
tients with a prior history of depression, poor premorbid function, and isola-
tion, but probability is not related to severity of the stroke itself (Ouimet et al.
2001). If untreated, poststroke depression contributes to diminished long-
term social and motor function, as well as increased mortality, with odds ratios
of 3.1 at 12 months and 2.2 at 24 months (House et al. 2001).

Anxiety
Anxiety occurs in about 25% of poststroke patients and more often than not
is accompanied by comorbid depression (Carson et al. 2011).

Cognitive Impairment
Cognitive impairment, including dementia, occurs in 25% of poststroke pa-
tients (Carson et al. 2011).
458 Clinical Manual of Psychosomatic Medicine

Behavioral Changes
Some behavioral changes correlate approximately to the location of the stroke
lesion and may overlap with the symptoms of specific psychiatric disorders
(Huffman et al. 2010):

• Orbitofrontal region—disinhibition and irritability

• Dorsolateral frontal lobe—executive dysfunction
• Medial frontal lobe—apathy and abulia
• Left frontal lobe—nonfluent (Broca’s) aphasia
• Left temporal lobe—fluent (Wernicke’s) aphasia and short-term memory
impairment to verbal and written stimuli
• Left parietal lobe—acalculia, agraphia, and right/left disorientation
• Right frontal lobe—motor dysprosody
• Right temporal lobe—sensory dysprosody and short-term memory im-
pairment to nonverbal stimuli (e.g., music)
• Right parietal lobe—anosognosia, constructional apraxia, and hemineglect
• Occipital lobes—cortical blindness with unawareness of the visual distur-
bance

Other Behavioral Phenomena

Pseudobulbar affect. Pseudobulbar affect, also described as emotional in-
continence, occurs in multiple neurological conditions that affect the central
nervous system and is characterized by incongruent episodes of laughter or
crying that erupt without the control of the patient, often in inappropriate
settings that prompt frustration and embarrassment, and that do not corre-
spond to any experience of relief at having expressed felt emotion on the part
of the patient (Chriki et al. 2006).
Catastrophic reaction. Catastrophic reaction typically includes an outburst
of anger, frustration, desperation, and acute dysphoria in the poststroke pe-
riod when the individual is confronted with either a change or a challenge,
such as moving from one’s home to a skilled nursing facility. The incidence
may be higher in individuals with a history of psychiatric illness and left-
hemispheric involvement; catastrophic reaction overlaps considerably but not
completely with poststroke depression (Huffman et al. 2010).
 Rehabilitation Medicine 459

Poststroke fatigue. Poststroke fatigue, which is distinct from depression and

characterized by early exhaustion after physical or mental activity and conse-
quent aversion to activity, occurs in 25%–50% of poststroke patients and may
significantly inhibit rehabilitation effort; basal ganglia and brain stem strokes
are associated with greater risk (Annoni et al. 2008; Tang et al. 2010).

Treatment
Depression and Anxiety
Antidepressants. SSRIs and TCAs are effective for poststroke depression, as
demonstrated in several placebo-controlled trials. SSRIs may be better toler-
ated and have the potential advantage of contributing to reduced platelet ag-
gregation (Bhogal et al. 2005; Hackett et al. 2005; Ramasubbu and Patten
2003; Starkstein et al. 2008). Although less well studied, venlafaxine proved
effective in a small series, and only two of 30 patients experienced an increase
in blood pressure (Kucukalic et al. 2007); mirtazapine has also been shown to
be effective (Niedermaier et al. 2004). A meta-analysis from 16 randomized
placebo-controlled trials suggested that the duration of antidepressant use be-
yond the initial month was associated with incremental further improvement
(Chen et al. 2006).

Stimulants. Uncontrolled prospective and retrospective studies support the

efficacy and tolerability of stimulants in patients with poststroke depression
(Grade et al. 1998; Masand and Tesar 1996). Stimulants have the advantage of
more rapid onset of benefit, thereby facilitating patient motivation and col-
laboration with physical therapy and other rehabilitative efforts.

Benzodiazepines. Benzodiazepines can relieve anxiety but are not effective

for comorbid depression and may impede rehabilitation by blunting cogni-
tion and contributing to gait instability.

Cognitive-behavioral therapy. Uncontrolled studies of cognitive-behavioral

therapy for poststroke depression have been inconclusive (Lincoln and Flan-
naghan 2003; Starkstein et al. 2008), but a randomized controlled trial of
problem-solving therapy suggested probable benefit in preventing depression
over the first year after a stroke (Robinson et al. 2008).
460 Clinical Manual of Psychosomatic Medicine

Cognitive Impairment
Although many studies have been designed to clarify whether pharmacother-
apy can enhance natural neuroplasticity and recovery, definitive data are lack-
ing. Low-dose levodopa may improve recovery from aphasia (Seniow et al.
2009), and noradrenergic and dopaminergic agents appear to hold the most
promise among other options (Czlonkowska and Lesniak 2009). Conversely,
use of dopamine antagonists and benzodiazepines ought to be avoided (Czlon-
kowska and Lesniak 2009) unless clearly necessary. In poststroke patients, esci-
talopram improved motor and cognitive outcome at 12 months, independent
of its effect on depression (Jorge et al. 2010). Other studies have shown that
both SSRIs and TCAs improve cognitive function when comorbid depression
is present (Kimura et al. 2000).

Pseudobulbar Affect
In small trials of patients, TCAs and SSRIs have proved helpful for treating
pseudobulbar affect, even in the absence of depression. Dextromethorphan/
quinidine combinations (the latter serves only as an inhibitor of dextrometho-
rphan metabolism) have also demonstrated efficacy (Rosen and Cummings
2007).

Poststroke Fatigue
Poststroke fatigue was not alleviated by fluoxetine, but modafinil may prove
helpful in patients with brain stem and diencephalic stroke (Brioschi et al.
2009).

Spinal Cord Injury

Although devastating, spinal cord injury (SCI) is relatively uncommon (about
1.25 million Americans are currently affected). Each of the following catego-
ries accounts for about 25% of all SCIs: motor vehicular accidents, occupa-
tional accidents, sporting and recreational injury, and falls (Carson et al. 2011;
“One degree of separation” 2009). Males are twice as likely to be affected as fe-
males, and more than half of SCI patients are less than age 30 years at the time
of injury. Half of all SCIs result in paraplegia and the other half in quadriple-
gia. Improved life expectancy translates into prolonged financial and caregiver
burdens.
 Rehabilitation Medicine 461

Psychiatric Comorbidities
Prompt psychiatric consultation is recommended when patients with SCI
have any of the following comorbidities: alcohol abuse and dependence, de-
pression, PTSD, or sexual dysfunction.

Alcohol Abuse and Dependence

Problematic drinking prior to injury (up to 50%) and intoxication at the time
of injury (up to 40%) identify patients with SCI whose long-term outcome
may be improved by initiating discussion of the role of alcohol use and the
benefits of moderation, if not abstinence (Bombardier 2000; Turner et al.
2003).

Depression
Depression in patients with SCI presents a paradoxical challenge: although
depression is prevalent in 25% of patients with SCI and is associated with in-
creased morbidity and mortality, multiple studies have shown that caregivers
expect depression to occur much more frequently and therefore both overes-
timate its occurrence and conclude that its absence betrays denial. Perversely,
this expectation or normalization of depression may also lead to undertreat-
ment in patients who do meet diagnostic criteria for major depression (Fann
et al. 2011).

Posttraumatic Stress Disorder

PTSD is rare in individuals with quadriplegia but occurs in 20% of those with
paraplegia; this disparity may reflect decreased awareness of physiological
arousal in those with higher-level lesions. PTSD may be more likely to occur
in those whose SCI was sustained in combat or who had prior exposure to vio-
lence (Kennedy and Duff 2001).

Sexual Dysfunction
Sexual dysfunction is commonly addressed by occupational therapists working
with patients with SCI. The level and completeness of injury determine the de-
gree of difficulty with lubrication in women, and of erectile and ejaculatory
function in men. The capacity to experience orgasm may approach 50% in
men and women, independent of injury characteristics (Fann et al. 2011). Sub-
stantive assessment and treatment strategies exist (Basson and Rees 2011).
462 Clinical Manual of Psychosomatic Medicine

Treatment
Treatment studies for psychiatric disorders in patients with SCI are uncom-
mon. Psychiatrists must treat patients based on thoughtful integration of the
known physiological sequelae of SCI and knowledge about the mechanism of
action and likely side effects of various medications.
Pharmacological Agents
Patients with SCI are liable to gain weight and develop glucose intolerance and
decreased gastrointestinal motility; they are also at increased risk of orthostasis
and venous thrombosis (Fann et al. 2011). These are reasons to prefer SSRIs
over TCAs, and perhaps bupropion over mirtazapine. Antispasticity agents are
often sedating, emphasizing the potential merit of activating rather than sopo-
rific antidepressants.
Psychological Assistance
The preponderance of young, active patients and the circumstances under which
SCIs occur may imbue the disability with particular meaning for patients; for ex-
ample, feelings of self-recrimination and guilt are possible. These feelings deserve
attention and may provide an opportunity for illustrating the practical value of de-
veloping cognitive-behavioral skills. For individuals whose premorbid routine in-
cluded high activity levels, effective intervention and collaboration with the reha-
bilitation team may benefit from deliberate use of cognitive-behavioral therapy to
reinforce participation in physical and occupational therapies.

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 28
Transplantation

More than 20,000 transplantations occur in the United States each year,
and well over 100,000 individuals are on waiting lists. Psychosomatic medicine
psychiatrists commonly participate in consultations during pretransplant, peri-
operative, recovery, and posttransplant periods. The degree to which the psy-
chiatrist is accepted as a member of the transplant team depends on several
factors (Skotzko and Strouse 2002): the ability to communicate effectively and
succinctly with other team members; the extent to which his or her clinical
judgment is trusted; the ability to effectively defuse adverse transplant team
member reactions to patients; and the ability to work collaboratively and ef-
fectively with other transplant team members.

General Issues
Psychiatric Symptoms
Long waits for transplants and graft survival rates (e.g., 10-year graft survival
rates of 35% for kidneys and 45% for livers) create stresses for transplantation
candidates, recipients, and families (DiMartini et al. 2011). The biological
manifestations of organ failure and the treatments administered as part of or-

467
468 Clinical Manual of Psychosomatic Medicine

gan failure and transplantation care cause significant neuropsychiatric mor-

bidity during all phases of care of transplantation candidates and patients.

Health Systems
Psychiatric factors such as psychotic symptoms, personality disorders, social
support, and substance use patterns are related to transplantation outcome
measures in positive and negative directions (Kotlyar et al. 2008). Psychiatric
consultation findings are associated with medical outcomes, including length
of stay, readmission duration, adherence with medications, and even mortal-
ity (Foster et al. 2009). Psychosomatic medicine psychiatrists have important
roles in helping the transplant team manage psychiatric symptoms and disor-
ders that impact outcomes.

Patient Categories
Research related to psychiatric factors that are important in transplantation out-
comes has focused mostly on kidney, liver, and heart transplantations, which ac-
count for almost 90% of all solid organ transplants performed in the United States
(DiMartini et al. 2011). Over 11,000 kidney transplants are performed annually,
compared with about 4,000 liver transplants, 3,600 bone marrow transplants,
2,000 heart transplants, 1,800 pancreas transplants, and 900 lung transplants (Di-
Martini et al. 2011). Most transplantation psychiatry programs in the United
States conceptualize their consultative practices around pretransplantation, perio-
perative and postsurgical recovery, and posttransplantation periods.

Pretransplantation Issues
End-Organ Failure
Neuropsychiatric differential diagnosis and psychopharmacological manage-
ment can be quite complicated in patients being evaluated for transplantation
with organ failure, and in patients with organ failure who do not qualify for or
who do not receive transplants. The medications usually recommended by
psychosomatic medicine psychiatrists to treat psychiatric symptoms may re-
quire significant caution and alteration in the setting of end-organ failure.
Renal Disease
Reduced renal clearance requires avoidance (or careful monitoring when use is
necessary) of medications predominantly excreted by the kidneys; these medica-
 Transplantation 469

tions include lithium, gabapentin, topiramate, and methylphenidate (DiMartini

et al. 2011). In addition, some psychotropic medications, including venlafaxine,
have active metabolites that are excreted largely by the kidneys. Hypoalbumine-
mia associated with renal disease can increase free drug concentrations.
Liver Disease
Pharmacological issues. Loss of liver tissue and decreased hepatic perfusion
decrease metabolism of medications, effectively raising drug levels. This ele-
vation in drug levels, in turn, heightens risks of increased liver toxicity and
drug adverse effects and interactions. Therefore, doses of psychiatric medica-
tions, when used, are reduced 25%–75% from usual levels, depending on the
degree of liver disease (DiMartini et al. 2011).
Hepatic encephalopathy. Hepatic encephalopathy is characterized by altered
consciousness, cognitive impairment, and disorientation, and may include affec-
tive lability, perceptual disturbances, and asterixis. A fluctuating course is the pat-
tern. Treatment focuses on reducing the production and absorption of ammonia.
Lactulose is an osmotic laxative that is usually an effective treatment.
Heart Disease
Diminished cardiac capacity may lead to “third spacing” and increased vol-
ume of distribution of drugs into interstitial tissues, resulting in decreased
drug metabolism and clearance (Shammas and Dickstein 1988). Hepatically
cleared drugs are more affected in heart failure than are renally cleared drugs.
Lung Disease
Acute hypoxia may reduce splanchnic blood flow to the liver, decreasing drug
metabolism and increasing drug levels. Hypoxia may also lead to reduced re-
nal blood flow.

Psychiatric Pretransplantation Evaluation

Donor Evaluations
Heart transplants involve brain-dead donors; other types of transplants fre-
quently involve living family donors. The consulting psychiatrist should eval-
uate potential interpersonal, marital, or family problems encountered by donor
families. For example, the psychiatrist should consider whether a family’s
“black sheep” is donating out of a conscious or an unconscious desire to im-
prove his or her standing in the family system.
470 Clinical Manual of Psychosomatic Medicine

Kidney donors. Living donors now outnumber cadaver donors for kidney
transplants (DiMartini et al. 2011). The mortality rate for kidney donors is
very low, calculated to be 0.03% (Surman and Prager 2004). Although pre-
operative donor anxiety may occur, it is generally self-limited when donors are
psychiatrically screened beforehand (Surman and Prager 2004).
Liver donors. For right hepatic lobe liver donation by a living donor, mor-
bidity is only about 1%, although medical complications occur in 36% and se-
rious complications in 15%, reinforcing the need for careful psychiatric con-
sultation (DiMartini et al. 2011) to assure appropriateness of candidacy for
donation. Although psychiatric complications following liver donation are un-
common (4%) when donors are psychiatrically screened (Trotter et al. 2007),
they may be serious and include suicidal behaviors. Postdonation mental health
and quality of life outcomes are poorer for patients with predonation psychiat-
ric diagnoses (DuBay et al. 2009). Although predonation psychiatric diagnoses
do not exclude a patient from being a donor, psychiatrists should remain avail-
able for support to donors following transplantation procedures, especially
when there are preexisting psychiatric issues.

Transplantation Recipient Evaluation

The psychiatric consultant on the transplant team conducts a wide-ranging
evaluation of potential transplantation recipients. The presence or absence of
a psychiatric disorder is only one factor in the overall assessment. Successful
transplantation outcomes have been reported in patients who have mental re-
tardation, anxiety disorders, mood disorders, substance use disorders, and per-
sonality disorders (Surman and Prager 2004). Factors such as allograft success,
strength of social supports, and history of medical treatment adherence are
also important considerations in behavioral evaluation of potential organ re-
cipients.
Absolute contraindications.

• Active substance abuse

• Psychosis that limits capacity for informed consent or adherence
• Active suicidal ideation
• Factitious disorder with physical symptoms
 Transplantation 471

• Consistent nonadherence to medical treatment

• Unwillingness to participate in necessary psychiatric treatment
• Unstable current mania

Relative contraindications.

• Dementia or other persistent cognitive dysfunction

• Inadequate psychosocial resources to support adherence
• Treatment-resistant mood disorder
• Schizophrenia
• Personality disorder with consequences for adherence
• Eating disorder
• Prominent and unmanageable behavioral dyscontrol
• Treatment-refractory psychiatric illness

Rating scales. Two scales are available for the clinical categorization of readi-
ness for organ transplantation from a psychiatric perspective: the Psychosocial As-
sessment of Candidates for Transplantation (PACT; Olbrisch et al. 1989) and the
Transplant Evaluation Rating Scale (TERS; Twillman et al. 1993). Both scales
weight or consider psychiatric diagnoses, substance abuse, health behaviors, ad-
herence, social support, and coping mechanisms. Both the PACT and TERS have
good interrater reliability and predictive power (Skotzko and Strouse 2002).

Perioperative and Postsurgical

Recovery Period Issues
Delirium and Other Secondary Psychiatric Disorders
Transplantation recipients are at risk for postoperative delirium and other sec-
ondary psychiatric disorders due to any of the following: existing central ner-
vous system consequences of organ failure; the residua of general anesthesia;
sometimes lengthy transplant surgery; volume and electrolyte shifts associated
with surgery and perfusion of the new organ; postoperative opiate analgesia;
effects of transplantation-specific medications, such as cyclosporine; and the
potential complications of coagulopathy, fever, and infections.
472 Clinical Manual of Psychosomatic Medicine

Neuropsychiatric Effects of
Immunosuppressive Medications
Cyclosporine
Tremor, restlessness, and headaches are common in patients taking cyclospor-
ine. Up to one-third of patients may experience more severe side effects, such
as seizures, delirium, or psychosis (DiMartini et al. 2011). Rare but poten-
tially life-threatening side effects include central pontine myelinolysis and
brain abscess.

Tacrolimus
Although the neuropsychiatric adverse effects of tacrolimus are similar to
those of cyclosporine, they occur less frequently (Emiroglu et al. 2009). In-
travenous administration may increase the relative risk, and the effects are
dose related.

Mycophenolate Mofetil
Although considered better tolerated than its predecessor azathioprine, myco-
phenolate is nevertheless associated with neuropsychiatric symptoms in 3%–
20% of transplant recipients who receive it. Effects include anxiety, depres-
sion, delirium, seizures, paresthesias, neuropathy, psychosis, and somnolence
(DiMartini et al. 2011). The precise contribution of this medication to neuro-
psychiatric syndromes is hard to define because it is often given in combina-
tion with tacrolimus or cyclosporine.

Corticosteroids
High-dose steroids may be used in the acute postoperative period to treat
acute rejection. Psychiatric side effects of corticosteroids may include dose-
related delirium, psychosis, and mood changes.

Drug Interactions
Tacrolimus, mycophenolate, and cyclosporine are each largely metabolized by
cytochrome P450 (CYP) 3A4. Psychotropic medications that inhibit this en-
zyme should be avoided; these include fluvoxamine, nefazodone, fluoxetine,
sertraline, most tricyclic antidepressants, escitalopram, desvenlafaxine, and
venlafaxine. In particular, fluvoxamine and nefazodone should be avoided due
 Transplantation 473

to the potential for potent enzyme inhibition. As of now, because CYP3A4

cannot be reliably tested pharmacogenomically, clinical knowledge and judg-
ment are necessary to avoid potentially life-threatening drug interactions.

Posttransplantation Issues
Transplantation and Quality of Life
The physical benefits of transplantation have a markedly positive impact on post-
transplantation psychological functioning and quality of life (Bravata et al. 1999;
Vermuelen et al. 2009). Quality of life is an important outcome cited by patients
in terms of reasons for pursuing transplantation to start with. Particularly for
transplantations with relatively limited long-term survival (i.e., lung and heart
transplants), quality of life and psychosocial functioning are important elements
to weigh in the decision to have a transplant (Barbour et al. 2006).

Psychiatric Disorders and Posttransplantation Outcomes

Effect on Survival
Psychiatric disorders affect survival. Posttransplantation survival can be short-
ened by the presence of psychiatric illness, especially depression (Havik et al.
2007; Owen et al. 2006). Neurotoxic effects of immunosuppressive medica-
tions are more frequent in patients with excessive alcohol use prior to trans-
plantation (DiMartini et al. 2008).

Risk of Resuming Risky Health Behaviors

The risk of postoperative resumption of risky health behaviors that were as-
sociated with the original end organ disease is significant. For example, 5%–
20% of liver transplant recipients who had alcoholic liver disease may relapse
to alcohol the first year after transplantation (Dew et al. 2008; DiMartini et al.
2006), and 15% or more of smokers who receive heart transplants may start
smoking again (Nagele et al. 1997). Risk of alcohol use after liver transplant
must be continually monitored.

Immunosuppressive Drug–Related Neuropsychiatric Syndromes

Immunosuppressive drugs can cause chronic neuropsychiatric syndromes.
The use of chronic immunosuppressive drugs may be responsible for psycho-
474 Clinical Manual of Psychosomatic Medicine

pathology that will need to be managed in ongoing psychiatric care that oc-
curs in concert with posttransplantation medical care. The same precautions
about neuropsychiatric adverse effects of medication and about drug interac-
tions apply throughout the posttransplantation period, even when chronic
immunosuppressant medication doses have equilibrated.

References
Barbour KA, Blumenthal JA, Palmer SM: Psychosocial issues in the assessment and
management of patients undergoing lung transplantation. Chest 129:1367–
1374, 2006
Bravata DM, Olkin I, Barnato AE, et al: Health-related quality of life after liver trans-
plantation: a meta-analysis. Liver Transpl Surg 5:318–331, 1999
Dew MA, DiMartini AF, Steel J, et al: Meta-analysis of risk for relapse to substance use
after transplantation of the liver or other solid organs. Liver Transpl 14:159–172,
2008
DiMartini A, Day N, Dew MA, et al: Alcohol consumption patterns and predictors of
use following liver transplantation for alcoholic liver disease. Liver Transpl
12:813–820, 2006
DiMartini A, Fontes P, Dew MA, et al: Age, model for end-stage liver disease score, and
organ functioning predict posttransplant tacrolimus neurotoxicity. Liver Transpl
14:815–822, 2008
DiMartini AF, Sotelo JL, Dew MA: Organ transplantation, in The American Psychi-
atric Publishing Textbook of Psychosomatic Medicine, 2nd Edition. Edited by
Levenson JL. Washington, DC, American Psychiatric Publishing, 2011, pp 725–
758
DuBay DA, Holtzman S, Adcock L, et al: Adult right-lobe living liver donors: quality
of life, attitudes, and predictors of donor outcomes. Am J Transplant 9:1169–
1178, 2009
Emiroglu R, Ayvaz I, Moray G, et al: Tacrolimus-related neurologic and renal compli-
cations in liver transplantation: a single-center experience. Transplant Proc
38:619–621, 2009
Foster LW, McLellan L, Rybicki L, et al: Utility of the Psychosocial Assessment of Can-
didates for Transplantation (PACT) scale in allogeneic BMT. Bone Marrow
Transplant 44:375–380, 2009
Havik OE, Sivertsen B, Relbo A, et al: Depressive symptoms and all-cause mortality af-
ter heart transplantation. Transplantation 84:97–103, 2007
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Kotlyar DS, Burke A, Campbell MS, et al: A critical review of candidacy for orthotopic
liver transplantation in alcoholic liver disease. Am J Gastroenterol 103:734–743,
2008
Nagele H, Kalmar P, Rodiger W: Smoking after heart transplantation: an underesti-
mated hazard? Eur J Cardiothorac Surg 12:70–74, 1997
Olbrisch ME, Levenson J, Hamer R: The PACT: a rating scale for the study of clinical
decision making in psychosocial screening criteria for organ transplant candi-
dates. Clin Transplant 3:164–169, 1989
Owen JE, Bonds CL, Wellisch DK: Psychiatric evaluations of heart transplant candi-
dates: predicting post-transplant hospitalizations, rejection episodes, and sur-
vival. Psychosomatics 47:213–222, 2006
Shammas FV, Dickstein K: Clinical pharmacokinetics in heart failure: an updated re-
view. Clin Pharmacokinet 15:94–113, 1988
Skotzko CE, Strouse TB: Solid organ transplantation, in The American Psychiatric
Publishing Textbook of Consultation-Liaison Psychiatry: Psychiatry in the Med-
ically Ill, 2nd Edition. Edited by Wise MG, Rundell JR. Washington, DC, Amer-
ican Psychiatric Publishing, 2002, pp 623–655
Surman OS, Prager LM: Organ failure and transplantation, in Massachusetts General
Hospital Handbook of General Hospital Psychiatry, 5th Edition. Edited by Stern
TL, Fricchione GL, Cassem NH, et al. St. Louis, MO, Mosby, 2004, pp 641–670
Trotter JF, Hill-Callahan MM, Gillespie BW: Severe psychiatric problems in right he-
patic lobe donors for living donor liver transplantation. Transplantation 83:1506–
1508, 2007
Twillman RK, Manetto C, Wolcott DL: The Transplant Evaluation Rating Scale: a re-
vision of the psychosocial levels system for evaluating organ transplant candi-
dates. Psychosomatics 34:144–153, 1993
Vermuelen KM, van der Bij W, Erasmus ME, et al: Long-term health-related quality of
life after lung transplantation: different predictors for different dimensions.
J Heart Lung Transplant 26:188–193, 2009
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 Index
Page numbers in boldface type refer to tables or figures.

AA (Alcoholics Anonymous), 250 Acquired immunodeficiency syndrome

ABMS (American Board of Medical (AIDS), 399–408.
Specialties), 4 See also Human immunodeficiency
ABPN (American Board of Psychiatry virus disease
and Neurology), 4 Acting out, 61–62
Absorption of drug, 274 Acute respiratory distress syndrome,
after bariatric surgery, 320, 324, 442
325–327 Acute stress disorder (ASD), 83–84
Abstraction, assessment of, 38–39 in disaster and terrorism casualties,
Abulia, 458 354
Academy of Psychosomatic Medicine treatment of, 93
(APM), 4 Acyclovir, 101
Acalculia, 458 AD. See Alzheimer’s disease
Acamprosate, for alcoholism, 251 Addenbrooke’s Cognitive Examination–
Accreditation Council for Graduate Revised (ACE-R), 40
Medical Education (ACGME), Addison’s disease, 366
4 Adherence to treatment, 210
ACE-R (Addenbrooke’s Cognitive anxiety after myocardial infarction
Examination–Revised), 40 and, 333
Acetaminophen in asthma, 444
for fibromyalgia, 381 bariatric surgery and, 323, 324
intentional overdose of, 71 in chronic obstructive pulmonary
ACGME (Accreditation Council for disease, 442
Graduate Medical Education), in depression, 161–162, 163
4 cardiac outcomes and, 331
Acid-base balance abnormalities, 101 with highly active antiretroviral
ACLS (advanced cardiovascular life therapy, 404
support), 351 hypnosis and/or relaxation for
Acne, 345 enhancement of, 313

477
478 Clinical Manual of Psychosomatic Medicine

Adherence to treatment (continued) in delirium tremens, 253

with psychotropic drug therapy, in HIV disease, 401
273–274 pharmacotherapy for, 139–141
doctor–patient relationship and, during sedative-hypnotic
273, 406 intoxication, 258
education for, 274 suicide and, 73
Adjustment disorder Agnosia, 120
with anxiety, 84 Agoraphobia, 431
somatic symptoms of, 214 without panic disorder, 83
Adrenal insufficiency, 101, 366 Agraphia, 458
Advance directives, 13–14, 19–20 AIDS (acquired immunodeficiency
Advanced cardiovascular life support syndrome), 399–408.
(ACLS), 351 See also Human
Advanced sleep phase disorder, immunodeficiency virus disease
203–204 Air hunger, 441
Advanced trauma life support (ATLS), Akathisia, 82, 85, 90
350–351 Alanine transaminase (ALT), 257
Affect Alcohol use/abuse, 82, 247–257
appropriateness of, 35 beverage alcohol content, 247
assessment of, 34–35 dementia and, 122
intensity of, 34 by disaster and terrorism casualties,
isolation of, 66 357
lability of, 34 eating disorders and, 148
negative, 148 epidemiology of, 245, 247
pseudobulbar, 454, 458, 460 head trauma and, 454
range of, 34 insomnia and, 198
reactivity of, 35 intoxication due to, 247–248
Age. See also Elderly persons laboratory testing for, 256–257
dementia and, 119, 121, 122 blood alcohol level, 247, 248,
depression and, 160 257
spinal cord injury and, 460 medical complications of, 250–251
traumatic brain injury and, 452 opiate dependence and, 260
Aggression overdose due to, 251–252
in Alzheimer’s disease, 123 in pregnancy, 412
in frontotemporal dementia, 129 psychosis induced by, 252
passive, 66 screening tools for, 254–256
pharmacotherapy for, 139–141 spinal cord injury and, 461
Agitation suicide and, 70, 71, 74, 254
in Alzheimer’s disease, 123 tuberculosis and, 447
 Index 479

Wernicke-Korsakoff syndrome and, Amenorrhea, 146, 151

152, 250, 253–254 American Board of Medical Specialties
withdrawal from, 248–250 (ABMS), 4
delirium during, 253 American Board of Psychiatry and
management of, 249–250 Neurology (ABPN), 4
seizures during, 252–253 American Psychiatric Association
symptoms of, 248–249 (APA), 4
Alcohol Use Disorders Identification γ-Aminobutyric acid (GABA), in
Test (AUDIT), 255 anxiety, 80
Alcoholics Anonymous (AA), 250 Aminoglutethimide, 101
Alkalosis, 101 Aminophylline, 82
Alprazolam, 88 Amitriptyline
for anxiety in cancer, 432 cardiac effects of, 290
discontinuation of, 91 for fibromyalgia, 380
for panic disorder, 91 for insomnia, 201
withdrawal from, 259 Amnesia. See also Memory impairment
ALT (alanine transaminase), 257 posttraumatic, 453
Alzheimer’s disease (AD), 72. sedative-, hypnotic-, or anxiolytic-
See also Dementia induced persisting, 259
caregivers for patients with, 123 Amphetamines, 82, 100, 101
clinical features of, 122–123 abuse of, 261–264
diagnostic criteria for, 124–125 complications of, 263–264
genetic factors in, 122 intoxication with, 262–263
medical conditions associated with, delirium during, 263–264
122 mechanism of action of, 261
mild cognitive impairment and, 121 medical uses of, 262
neuroimaging in, 135 narcolepsy, 203
neuropsychiatric symptoms of, 123 psychosis induced by, 264
pathophysiology of, 122 street names for, 264
prevalence of, 122 withdrawal from, 263
treatment of (See Dementia Amphotericin B, 101
treatment) Amygdala, 81
vascular dementia and, 123 β-Amyloid, 122
AMA discharge. See Signing out against Analgesics, 101
medical advice for fibromyalgia, 381
Amantadine, 101 Anastrozole, 435
for neuroleptic malignant Anemia, 82, 102, 250
syndrome, 289 Anesthetic agents, malignant
in traumatic brain injury, 456 hyperthermia and, 286–287, 288
480 Clinical Manual of Psychosomatic Medicine

Anger, suicide and, 73 for mania, 184–185

Angina, 81, 122 in HIV disease, 407
nocturnal, 196 in pregnancy and postpartum
tricyclic antidepressants and, 172 period, 421
Anhedonia, 163 for pain disorder, 235
Anorexia, in depression, 162 in traumatic brain injury, 456
Anorexia-cachexia syndrome in cancer, Antidepressants, 169–177.
435 See also specific drugs and classes
Anorexia nervosa. adverse effects of
See also Eating disorder(s) anxiety, 82
course of, 147 mania, 185
diagnostic criteria for, 146 in neonates, 419
diagnostic overlap with other eating pancreatic injury, 394
disorders, 145 for agitation in dementia, 141
medical complications of, 149–152, for anxiety
151 acute anxiety and generalized
mortality and, 148 anxiety disorder, 87
prevalence of, 147 acute stress disorder, 93
psychiatric comorbidity with, 148 in chronic obstructive
subtypes of, 145, 146 pulmonary disease, 442
treatment of, 153–154 health anxiety, 93
inpatient care, 153 panic disorder, 91
pharmacological and behavioral posttraumatic stress disorder, 93
interventions, 154 social anxiety disorder, 92
refeeding syndrome and, augmentation of, 174, 364
153–154 during breast-feeding, 417, 419
Anti-inflammatory agents, 138 bupropion, 171
Antiarrhythmics, before in chronic fatigue syndrome, 377
electroconvulsive therapy, 295 for depression, 169–177
Anticholinergic agents, 82, 101, 448 in bipolar disorder, 185
toxicity of, 284, 286–287, 288 in cancer, 429–430
Anticipation, 64 in cardiovascular disease,
Anticonvulsants. 334–335
See also specific drugs in chronic obstructive
adverse effects of pulmonary disease, 443
delirium, 101 combined with psychotherapy,
pancreatic injury, 394 178
for agitation in dementia, 141 comparative efficacy and
for fibromyalgia, 380–381 tolerability of, 177
 Index 481

depression severity and effects of, delirium, 101

177 mania, 185
in diabetes mellitus, 362 orthostatic hypotension, 291
in disaster and terrorism for anxiety
casualties, 354 in chronic obstructive
in HIV disease, 406 pulmonary disease, 442
poststroke, 459, 460 panic disorder, 91
in spinal cord injury, 462 for depression, 171–172
in STAR*D study, 175–177 in cancer, 430
in thyroid disease, 364 in diabetes mellitus, 362
for fibromyalgia, 380 poststroke, 459, 460
for hot flashes in cancer, 169, 170, dosages of, 172
435 drug interactions with, 472
interaction with immunosuppressive for fibromyalgia, 380
agents, 472–473 for idiopathic pruritus, 342
for irritable bowel syndrome, 389 indications for, 171
in liver disease, 293 for insomnia, 201
mirtazapine, 171 for irritable bowel syndrome, 389
monoamine oxidase inhibitors, for pain disorder, 235
172–173 precautions for use of, 172
for obsessive-compulsive disorder, in pregnancy, 418
92 for pseudobulbar affect, 460
in pregnancy, 415–419, 416 in renal disease, 292
preterm birth and, 413 in spinal cord injury, 462
relapse risk with antidepressant in traumatic brain injury, 456
discontinuation, 414 Antihistamines, 101
in primary care settings, 10 for anxiety in cancer, 432
for pseudobulbar affect, 460 cardiac effects of, 291
in renal disease, 292 intentional overdose of, 71
selective serotonin reuptake Antimicrobial agents, 101, 291
inhibitors, 169–170 Antineoplastic agents, neuropsychiatric
adverse cardiac effects of, 290 effects of, 101, 435, 436–437
serotonin-norepinephrine reuptake Antiparkinsonian agents, 101
inhibitors, 170–171 Antipsychotics
in traumatic brain injury, 456 adverse effects of, 139–141
trazodone, 171 dysphagia, 386
tricyclic (TCAs), 171–172 hyperprolactinemia, 367
adverse effects of, 172, 362 metabolic syndrome, 141,
cardiac effects, 172, 289–290 291–292, 340
482 Clinical Manual of Psychosomatic Medicine

Antipsychotics, HIV-associated, 405

adverse effects of (continued) for delirium tremens, 253
myocarditis and for delusional psychocutaneous
cardiomyopathy, 291 disorders, 340, 341
in neonates, 422 for hyperemesis gravidarum,
neuroleptic malignant 421–422
syndrome, 285–289, in liver disease, 294
286–287 for mania, 185
orthostatic hypotension, 291 corticosteroid-induced, 182
pancreatic injury, 394 in HIV disease, 407
QTc interval prolongation, 112, with lithium, 183
113, 114, 115, 141, for pain disorder, 235
290–291, 340 during pregnancy and breast-
teratogenicity, 421–422 feeding, 421–422
for agitation and aggression in in renal disease, 293
dementia, 139–141 sensitivity to, in dementia with
for alcohol-induced psychotic Lewy bodies, 127
disorder, 252 in traumatic brain injury, 456
for amphetamine intoxication, 263, for trichotillomania, 344
264 Antiretroviral therapy.
for anorexia nervosa, 154 See Highly active antiretroviral
for antidepressant augmentation, therapy for HIV/AIDS
174 Antisocial personality disorder, 215
for anxiety malingering and, 237, 238
in cancer, 432 opiate dependence and, 260
in chronic obstructive Antispasmodics, 101
pulmonary disease, 442 Antispasticity agents, 462
generalized anxiety disorder, 90 Anxiety and anxiety disorders, 79–93
panic disorder, 91–92 acute stress disorder, 83–84
posttraumatic stress disorder, 355 adjustment disorder with anxiety, 84
in ventilator-dependent patients, agoraphobia without panic disorder,
445 83
for bipolar depression, 185–186 bariatric surgery and, 322
for cocaine-induced delirium or differential diagnosis of, 85
psychotic disorder, 267 in disaster and terrorism casualties,
for delirium, 26, 111–113 350, 354–355
dosage and administration of, epidemiology of, 80
112, 113, 113 generalized anxiety disorder, 82
evidence base for, 111–112 health anxiety, 84–85
 Index 483

health care utilization and, 79–80 social anxiety disorder, 83

medical illness and, 79, 80, 81, 86 somatic symptoms of, 214
asthma, 443 specific phobias, 83
cancer, 430–432, 432 speech in, 32
cardiovascular disease, 332–333 treatment and management of,
chronic obstructive pulmonary 86–93
disease, 442 acute anxiety and generalized
fibromyalgia, 379 anxiety disorder, 86–91,
gastroesophageal reflux disease, 88–89
386 acute stress disorder, 93
head trauma, 454, 455 anxiety disorder due to general
hepatitis C virus infection, 393 medical condition or
HIV disease, 404–405 substance, 86
inflammatory bowel disease, health anxiety, 93
390–391 hypnosis and/or relaxation, 91,
irritable bowel syndrome, 389 313
stroke, 457, 459 obsessive-compulsive disorder, 92
ventilator dependence, 444–445 panic disorder, 91–92
mental status examination in, 85 posttraumatic stress disorder, 93
neuroanatomy of, 81 social anxiety disorder, 92
neurophysiology of, 80 specific phobias, 92
neurotransmitters in, 80 Anxiolytics
nicotine withdrawal and, 442 abuse of, 257–259
noncardiac chest pain in, 83, 333, for acute anxiety and generalized
387 anxiety disorder, 86–90
obsessive-compulsive disorder, 83 antidepressants as, 87
panic disorder, 82–83 antipsychotics as, 90
postpartum, 412 benzodiazepines, 86–87, 88–89
posttraumatic stress disorder, 84 beta-blockers as, 90
in pregnancy, 412 buspirone, 87
psychiatric comorbidity with, 85 for health anxiety, 93
depression, 159 APA (American Psychiatric
eating disorders, 148 Association), 4
pain disorder, 234 Apathy, 53, 401, 458
secondary, 81–82 Aphasia, 38, 43, 46–47, 120
causes of, 81–82 poststroke, 458, 460
due to general medical Aphonia, 32
condition, 81, 86 APM (Academy of Psychosomatic
substance-induced, 81, 82, 86 Medicine), 4
484 Clinical Manual of Psychosomatic Medicine

Apolipoprotein E ε4 allele (APOE*E4), Clinical Institute Withdrawal

122 Assessment for Alcohol
Appearance (CIWA-Ar), 250
assessment of, 31–32 Clock Drawing Test, 41–42, 44, 106
preoccupation with, in body Confusion Assessment Method
dysmorphic disorder, 230 (CAM), 103, 103, 109
Appetite-suppressant abuse, 151 Delirium Rating Scale (DRS), 109
Apraxia, 120 Edinburgh Depression Scale, 414
Aripiprazole Epworth Sleepiness Scale, 197
for agitation and aggression in executive function tests, 44–46
dementia, 140 Frank Jones story test, 42
for antidepressant augmentation, 174 go–no go test, 45
cardiac effects of, 290 Hamilton Rating Scale for
for delusional parasitosis, 340 Depression (Ham-D17), 175
Arrhythmias, 79, 81, 102, 150 Hospital Anxiety and Depression
tricyclic antidepressants and, 172, Scale (HADS), 168
289–290 Luria three-step test, 45–46
Arthritis, 162, 390 Maintenance of Wakefulness Test
Articulation, 32 (MWT), 197
Ascites, 250 Marie Three Paper Test, 43
ASD. See Acute stress disorder Memorial Delirium Assessment
Asparaginase, 101, 436 Scale (MDAS), 109
Aspartate transaminase (AST), 257 mental status examination (MSE),
Aspiration, 98 31–39
Assessment instruments Michigan Alcohol Screening Test
Addenbrooke’s Cognitive (MAST), 255
Examination–Revised Mini-Mental State Examination
(ACE-R), 40 (MMSE), 22, 40, 134, 136,
Alcohol Use Disorders Identification 363
Test (AUDIT), 255 modified, 134
Beck Depression Inventory–II Minnesota Multiphasic Personality
(BDI-II), 167 Inventory, 217
Bender-Gestalt Test, 43 Montreal Cognitive Assessment
Blessed Dementia Scale, 43 (MoCA), 40, 134–135, 136
Brief Michigan Alcohol Screening Multiple Sleep Latency Test
Test (bMAST), 255–256 (MSLT), 197
CAGE screen, 255 Neuropsychiatric Inventory, 140
Center for Epidemiologic Studies Patient Health Questionnaire–9
Depression Scale (CES-D), 168 (PHQ-9), 169, 414
 Index 485

Postpartum Depression Screening Autonomic nervous system dysfunction

Scale, 414 during amphetamine intoxication,
Psychosocial Assessment of 263
Candidates for Transplantation in anxiety, 80
(PACT), 471 in delirium tremens, 253
Quick Inventory of Depressive in depression and cardiovascular
Symptomatology Self-Report disease, 332
(QIDS-SR), 175 in disaster and terrorism casualties,
Set Test, 42, 44 350
Short Test of Mental Status in neuroleptic malignant syndrome,
(STMS), 40, 134, 136 287
Stanford Sleepiness Scale, 197 in serotonin syndrome, 284
Trail Making Test, 40, 44 Avoidant personality disorder, 221
Transplant Evaluation Rating Scale
(TERS), 471
TWEAK questionnaire, 256 Backward-spelling test, 37
vigilance test, 43 Barbiturates, 71, 101
AST (aspartate transaminase), 257 abuse of, 257
Asthma, 79, 82, 441, 443–444 Bariatric surgery, 155, 319–327
anxiety disorders and, 443 contraindications to, 321–322
depression and, 443–444 criteria for, 320
epidemiology of, 443 medical assessment for, 320–321
Ataxia, 250, 253 nutritional deficiencies after, 320,
Ativan. See Lorazepam 367
ATLS (advanced trauma life support), pharmacokinetics after, 320, 324,
350–351 325–326
Atomoxetine. for cataplexy, 203 psychiatric assessment for, 321–324
Atopic dermatitis, 345–346 high rates of psychiatric disorders
Atrial fibrillation, 122 among bariatric surgery
Atropine, 101, 357 candidates, 322–323
Attention lack of evidence-based models or
assessment of, 37 consensus guidelines for,
deficits of, 37 321–322
in delirium, 105, 108 negative effects of presurgical
in dementia, 108 psychiatric disorders on
vascular dementia, 125 postsurgical weight loss,
in depression, 108 322
AUDIT (Alcohol Use Disorders psychological issues associated
Identification Test), 255 with poor outcomes, 323
486 Clinical Manual of Psychosomatic Medicine

Bariatric surgery (continued) administration routes for, 86

psychiatric management for, adverse effects of, 87, 200
325–327 congenital anomalies, 418
perioperative, 326 delirium, 101
postoperative, 326–327 in neonates, 418
preoperative, 325–326 for alcohol withdrawal, 249–250
types of, 319–320 delirium, 115, 253, 406
combined restrictive and seizures, 252
malabsorptive procedure, for anticipatory nausea/vomiting,
320 387
restrictive procedure, 319 for anxiety
BDD. See Body dysmorphic disorder acute anxiety and generalized
Beck Depression Inventory–II anxiety disorder, 86–87
(BDI-II), 167 in asthma, 443
Behavior therapy. in cancer, 432
See also Cognitive-behavioral in chronic obstructive
therapy; specific behavioral pulmonary disease, 442
interventions panic disorder, 91
for acne, 345 poststroke, 459
for anticipatory nausea/vomiting, selective serotonin reuptake
387 inhibitor–induced, 169
for atopic dermatitis, 346 chronic use of, 257–258
before bariatric surgery, 325 dependence on, 86, 234
for conversion disorder, 229 dosage of, 86, 88–89, 201
for generalized anxiety disorder, 91 for elderly persons, 86, 200, 432
for narcolepsy, 203 half-lives of, 86, 201
for nightmare disorder, 204 in HIV-associated delirium,
for obsessive-compulsive disorder, 405–406
92 for insomnia, 200, 201
for pain disorder, 235 with lithium for mania, 183
for panic disorder, 92 in liver disease, 294
for psoriasis, 345 for neuroleptic malignant
for specific phobias, 92 syndrome, 289
for trichotillomania, 344 overdose of, 71
Belladonna alkaloids, 101 flumazenil for, 258
Bender-Gestalt Test, 43 for periodic limb movement
Benzodiazepines (BZDs), 88–89 disorder, 205
abuse of, 257–259 during pregnancy and breast-
“shopping bag sign” of, 257 feeding, 418, 420
 Index 487

in renal disease, 293 Biopsychosocial model, 7

for serotonin syndrome, 285 Bipolar disorder, 34, 178–186.
for stroke patients, 459, 460 See also Mania
tolerance to, 86, 87, 257 diagnosis of, 179–182
in traumatic brain injury, 456 secondary mania, 180–182, 181
for ventilator-dependent patients, effects of medical comorbidity on
445 outcomes of, 179
withdrawal from, 87, 258–259 family history of, 179
neonatal, 418 mortality and, 179
Benztropine, 101, 386 postpartum psychosis and, 413
Beriberi, 152 prevalence of, 178–179
Beta-blockers recurrence of, 179
adverse effects of, 90, 101, 198 treatment of, 182–186
for anxiety, 90 for depression, 185–186
for cocaine intoxication, 266 for mania, 182–185
before electroconvulsive therapy, 295 in pregnancy and postpartum
for hyperventilation syndrome, 447 period, 420–421
Bevacizumab, 437 Blessed Dementia Scale, 43
Biliopancreatic diversion, 320. Blood alcohol level, 247, 248, 257
See also Bariatric surgery Blues, postpartum, 412
Billing, 6 bMAST (Brief Michigan Alcohol
Binge-eating disorder, 147 Screening Test), 255–256
diabetes mellitus and, 152 BMI (body mass index), 320, 322
duration of, 147 Body dysmorphia, delusions of, 215
prevalence of, 147 Body dysmorphic disorder (BDD),
treatment of, 155 230–233
bariatric surgery, 155, 322, 324 associated features of, 231
Biofeedback, 91 clinical course and prognosis for,
for acne, 345 232–233
for anxiety in pulmonary disease, clinical features of, 230
442, 443 psychocutaneous conditions,
for somatoform disorders, 220 341–342
Biological treatments, 273–296 differential diagnosis of, 231–232
deep brain stimulation, 295–296 epidemiology of, 230
electroconvulsive therapy, 294–295 management of, 233, 342
psychotropic drug therapy, 273–294 psychiatric comorbidity with, 231
transcranial magnetic stimulation, suicidality and, 232
295 Body image disturbance, in eating
vagal nerve stimulation, 295 disorders, 146
488 Clinical Manual of Psychosomatic Medicine

Body mass index (BMI), 320, 322 with periodic limb movement
Borderline personality disorder, 34 disorder, 205
Bosentan, for pulmonary hypertension, in STAR*D study, 176
446 drug interactions with, 429
Boundaries, 7 for inflammatory bowel disease, 392
Bradycardia, 150 in panic disorder, 91
Brain-gut axis, 385 in pregnancy, 418
Breast cancer, 430, 435 for smoking cessation, 443
Breast-feeding and medication use, 416 in traumatic brain injury, 456
antidepressants, 417, 419 Burn trauma, 101, 102
antipsychotics, 421–422 Buspirone
benzodiazepines, 420 advantages in medically ill patients,
mood stabilizers, 420–421 87
Brief Michigan Alcohol Screening Test adverse effects of, 87
(bMAST), 255–256 for antidepressant augmentation,
Broca’s aphasia, 458 174
Bromocriptine, 101 in STAR*D study, 176
for neuroleptic malignant for anxiety
syndrome, 289 in chronic obstructive
Bronchodilators, 442, 448 pulmonary disease, 442
Brudzinski’s sign, 46 generalized anxiety disorder, 87
Bulimia nervosa. dosage of, 87
See also Eating disorder(s) drug interactions with, 87
course of, 147 Butalbital, 257
diagnostic criteria for, 146 BZDs. See Benzodiazepines
diagnostic overlap with other eating
disorders, 145 CACS (cancer-related anorexia-
mortality and, 148 cachexia syndrome), 435
prevalence of, 147 Caffeine, 82, 198, 205
psychiatric comorbidity with, 148 CAGE screen, 255
treatment of, 154–155 Calcium channel blockers, 82
Buprenorphine, 261 Calcium intake, 150
Bupropion CAM (Confusion Assessment Method),
adverse effects of, 171, 392 103, 103, 109
for depression, 171, 174, 177 Cancer, 72, 159, 196, 374, 427–437
in bipolar disorder, 185 anorexia-cachexia syndrome of, 435
in cancer, 430 anxiety and, 430–432
in diabetes mellitus, 362 diagnosis of, 431
 Index 489

medical causes of, 431, 432 Carbamazepine

prevalence of, 430–431 adverse effects of, 184
treatment of, 431–432 teratogenicity, 421
delirium and, 98, 435 for agitation in dementia, 141
depression and, 427–430 drug interactions with, 184, 185
diagnosis of, 428 in liver disease, 294
medical consequences of, 429 for mania, 184
pharmacotherapy for, 429–430 in HIV disease, 407
prevalence of, 427 during pregnancy and breast-
psychotherapy for, 430 feeding, 421
risk factors for, 428 Carbidopa-levodopa, 198, 205.
suicide and, 428 See also Levodopa
end-of-life care in, 435–437 Carbohydrate-deficient transferrin, 257
fatigue related to, 433–434, 434 Carbon monoxide poisoning, 102
mania and, 432 Carcinoid syndrome, 82
neuropsychiatric effects of Cardiac medications, 101
antineoplastic agents for, 101, Cardiac Randomized Evaluation of
435, 436–437 Antidepressant and Psychotherapy
pain in, 433 Efficacy (CREATE), 335
treatment of hot flashes in, 169, Cardiopulmonary resuscitation (CPR),
170, 435 18–19, 446
Cannabis, 82, 100 Cardiovascular disease (CVD), 79, 81,
Capacity, 14, 20–23 102, 329–335
vs. competency, 20–21 anxiety and, 332–333
do-not-resuscitate or do-not- autonomic nervous system
intubate orders and, 19 dysfunction and, 332
documentation of, 22 bipolar disorder and, 179
encouraging documentation of central sleep apnea and, 202
wishes while patient has, dementia and, 122
22–23 depression and, 161, 162, 329–332
evaluation of patients who refuse cardiac surgery, 331
treatment, 20–21, 73–74 comorbidity mechanisms,
to give informed consent, 21 331–332
signing out against medical advice prevalence of comorbidity, 329
and, 17 prognostic significance, 330–
threshold to establish, 21–22 331
Capecitabine, 436 risk for onset of cardiovascular
Captopril, 101 disease, 330
490 Clinical Manual of Psychosomatic Medicine

Cardiovascular disease (CVD), Cataplexy, 203

depression and (continued) Catastrophic reaction, poststroke, 458
treatment of depression and Catatonia, 32, 178
reduction of cardiovascular malignant, 288, 289
risk, 334–335 in pregnancy, 418
eating disorders and, 150 CATIE-ADE (Clinical Antipsychotic
epidemiology of, 329 Trials of Intervention
hypothalamic-pituitary-adrenal axis Effectiveness–Alzheimer’s
in, 332 Disease), 140
implantable cardioverter- CBT. See Cognitive-behavioral therapy
defibrillator for, 333–334 Center for Epidemiologic Studies
inflammation and, 332 Depression Scale (CES-D), 168
left ventricular assist device for, 81, Central nervous system (CNS)
334 in anxiety, 80, 81
platelet activity and, 331 hepatitis C virus replication in, 393
psychotropic drug therapy in, 335, in HIV disease, 401–402, 405
469 infections of, 102
risk factors for, 331 lymphoma of, 402
Cardiovascular effects of drugs, 289–291 tumors of, 102
alcohol, 250 Central sleep apnea, 202
carbamazepine, 184 Centrax. See Prazepam
clozapine, 291 Cephalosporins, 101
cocaine, 265–266 Cerebral contusion, 452
lithium, 183 Cerebrovascular disease, 79, 81, 125.
orthostatic hypotension, 291 See also Stroke
psychostimulants, 174 central sleep apnea and, 202
QTc interval prolongation and dementia due to, 123, 125, 126
sudden cardiac death, CES-D (Center for Epidemiologic
289–291 Studies Depression Scale), 168
antipsychotics, 112, 113, CFS. See Chronic fatigue syndrome
114–115, 141, 290–291, Chemotherapy agents, neuropsychiatric
340 effects of, 101, 435, 436–437
tricyclic antidepressants, 172, 289 Chest pain, noncardiac, 83, 333, 387
syrup of ipecac, 150 Childbirth, 411–422.
tricyclic antidepressants, 172, See also Pregnancy
289–290, 335, 362 Childhood abuse/adversity
Cardiovascular effects of depression and, 161
electroconvulsive therapy, 295 gastroesophageal reflux disease and,
Carisoprodol, 257 386
 Index 491

irritable bowel syndrome and, 388 interferon-induced, 429

somatization disorder and, 221 in STAR*D study, 175–176
visceral hypersensitivity and, 385 for generalized anxiety disorder, 87
Chlorambucil, 436 in liver disease, 293
Chlordiazepoxide, 88 for posttraumatic stress disorder, 355
for alcohol withdrawal, 249 in pregnancy, 417
Chlorpromazine in renal disease, 292
for delirium, 111 CIWA-Ar (Clinical Institute
for delusional parasitosis, 340 Withdrawal Assessment for
Cholecalciferol deficiency, 368 Alcohol), 250
Cholinesterase inhibitors, for dementia, CL psychiatrist.
138, 141, 198 See Consultation-liaison
Chronic fatigue syndrome (CFS), psychiatrist
375–377 Claustrophobia, 83, 431
consensus criteria for, 375–376, 377 Clinical Antipsychotic Trials of
epidemiology of, 376 Intervention Effectiveness–
etiology of, 376 Alzheimer’s Disease (CATIE-AD),
history of, 375–376 140
irritable bowel syndrome and, 388 Clinical Institute Withdrawal
treatment of, 376–377 Assessment for Alcohol
Chronic obstructive pulmonary disease (CIWA-Ar), 250
(COPD), 72, 82, 374, 441–443 Clock Drawing Test, 41–42, 44, 106
anxiety disorders and, 442 Clomipramine
depression and, 442–443 for obsessive-compulsive disorder, 92
epidemiology of, 441 for onychophagia, 344
Chronotherapy, 204 for trichotillomania, 344
Cimetidine, 101 Clonazepam, 86, 88
Ciprofloxacin, 101 for benzodiazepine withdrawal, 259
Circadian rhythm sleep disorders, for insomnia, 201
203–204 with lithium for mania, 183
Circumstantiality, 33 for panic disorder, 91
Cirrhosis, 250, 393 Clonidine, 101
Cisplatin, 436 for hot flashes in cancer, 435
Citalopram, 170 for panic disorder, 92
adverse cardiac effects of, 290 Clorazepate, 88
for agitation in dementia, 141 Clozapine
for depression adverse effects of, 291, 294
in cardiovascular disease, 335 during breast-feeding, 416
in HIV disease, 406 CNS. See Central nervous system
492 Clinical Manual of Psychosomatic Medicine

Cocaine, 82, 100, 101, 264–267 other useful tests for, 41–44
complications of use, 266–267 Bender-Gestalt Test, 43
HIV disease and, 404 Blessed Dementia Scale, 43
intoxication with, 265–266 Clock Drawing Test, 41–42
delirium during, 266–267 Frank Jones story test, 42
mechanism of action of, 264 Marie Three Paper Test, 43
psychosis induced by, 267 Set Test, 42
street names of, 267 Trail Making Test, 40, 44
tolerance to, 264, 265 vigilance test, 43
toxicology screen for, 264–265 Cognitive-behavioral therapy (CBT),
withdrawal from, 266–267 312–313
Cognitive assessment, 36–46. for anxiety
See also Assessment instruments; acute stress disorder, 93
Mental status examination in asthma, 443
of abstraction, 38–39 in cancer, 431
of attention, 37 in chronic obstructive
bedside screening tools for, 39–40 pulmonary disease, 442
Addenbrooke’s Cognitive generalized anxiety disorder, 90
Examination–Revised, 40 health anxiety, 93
advantages and disadvantages of, panic disorder, 92
39 posttraumatic stress disorder, 93,
Mini-Mental Status 355
Examination, 40 for atopic dermatitis, 346
Montreal Cognitive Assessment, for body dysmorphic disorder, 233,
40 342
Short Test of Mental Status, 40 for chronic fatigue syndrome,
documentation of, 22 376–377
executive function tests, 44–46 for conversion disorder, 230
cognitive estimates, 45 for depression
go–no go evaluation of in cancer, 430
impulsivity, 45 in chronic obstructive
letter and category fluency, 44 pulmonary disease, 443
Luria three-step test, 45–46 in diabetes mellitus, 362
similarities, 45 in disaster and terrorism
general considerations, 36–37 casualties, 354
of language, 38 after myocardial infarction, 335
of level of consciousness and postpartum, 419
orientation, 37 poststroke, 459
of memory, 38 for eating disorders, 154–155
 Index 493

for fibromyalgia, 381 Communication

for hypochondriasis, 226 culture and, 302
for idiopathic pruritus, 342 language barriers and, 303
for inflammatory bowel disease, 392 interpreters for, 304–305
for insomnia, 198, 200 patient personality patterns and,
for irritable bowel syndrome, 389 54–64
for personality disorders in HIV with suicidal patient,
disease, 408 documentation of, 74
for psoriasis, 345 Community resources, 308
in spinal cord injury, 462 Competency. See also Incompetency
for trichotillomania, 344 vs. capacity, 20–21
Cognitive impairment/decline Compliance.
delirium, 97–116 See Adherence to treatment
dementia, 119–141 Comprehension, assessment of, 38, 43
in depression, 167 Computed tomography (CT)
in elderly patients, 36, 119 in dementia, 135, 137
head trauma and, 454, 455 diffuse axonal injury on, 453
HIV disease and, 401–402 in eating disorders, 149
mild, 121 Concentration problems
Mini-Mental Status Examination in delirium, 105
score and severity of, 40 in depression, 163
poststroke, 457, 460 in HIV disease, 401
sarcoidosis and, 446 Confidentiality, 8–9, 14–16
somatic symptoms of, 214 balancing patient privacy against
thyroid disease and, 363 consultee need to know, 15
Cognitive rehabilitation, 456 factitious disorders and, 237
Cognitive therapy. HIPAA and, 9, 14–15
See also Cognitive-behavioral limits on, 8
therapy obtaining patient permission before
for depression, 178 speaking with family/friends,
in STAR*D study, 176 15
for somatoform disorders, 220 sharing of medical records and, 8–9
Cognitive training, 137 statutory exceptions to, 15–16
Colitis, 389 Confusion Assessment Method (CAM),
Collaborative consultation, 10 103, 103, 109
Collagenous colitis, 389 Congestive heart failure, 72, 81, 102,
Commitment, involuntary, 24–25. 150, 154, 274, 291, 374
See also Involuntary depression and, 330–331
hospitalization psychotropic drug therapy in, 469
494 Clinical Manual of Psychosomatic Medicine

Consciousness COPD. See Chronic obstructive

level of pulmonary disease
assessment of, 37 Coping
in delirium, 105 constructive, 65–66
in neuroleptic malignant defense mechanisms for, 64–65
syndrome, 287 demands exceeding resources for, 210
loss of, 453 educating patients in strategies for,
Conservator, 14 309
Consultation-liaison (CL) psychiatrist, maladaptive
3–11. depression and, 160–161
See also Psychosomatic medicine fibromyalgia and, 379
services Coronary heart disease, 79, 179, 196,
characteristics of effective 210, 321, 332.
consultants, 7 See also Cardiovascular disease
consultation style of, 8 Cortical blindness, 458
as neuropsychiatrist, 46–47 Corticosteroids
in outpatient settings, 5, 10–11 adverse effects of, 32, 82, 101, 391,
patient confidentiality and, 8–9, 436, 447–448, 472
14–16 antipsychotics for, 90
patient factors affecting response to, depression, 182, 391
51–54 insomnia, 198
patient follow-up by, 9, 307–308 mania, 182, 391, 432
reimbursement for services of, 4, 7, for cancer-related anorexia-cachexia
11 syndrome, 435
training of, 4, 5 deficiency of, 366
Conversion disorder, 212, 226–230 excess of, 366
associated features of, 227 for Hashimoto’s encephalopathy,
caveats for diagnosis of, 227 364–365
clinical course and prognosis for, for inflammatory bowel disease, 391
228–229 after transplant surgery, 472
clinical features of, 226–227 Corticotropin, 366
differential diagnosis of, 227–228 Cortisol, 151, 366
in disaster and terrorism casualties, Cosmetic surgery, 232, 233
356 Cost-effectiveness, 6
epidemiology of, 226 Countertransference, 54, 218
management of, 219, 229–230 Coup-contrecoup injuries, 452.
neurological examination in, 46–47 See also Traumatic brain injury
predisposing factors for, 228 CPR (cardiopulmonary resuscitation),
primary gain in, 226 18–19, 446
 Index 495

CREATE (Cardiac Randomized Delayed sleep phase disorder, 203

Evaluation of Antidepressant and Delirium, 97–116
Psychotherapy Efficacy), 335 in Addisonian crisis, 366
Creutzfeldt-Jakob disease, 130–131, alcohol withdrawal, 252, 253
137 amphetamine intoxication, 263–
Crohn’s disease, 389–392 264
Cryptococcal meningitis, 402 anticholinergic, 284, 286–287, 288
CT. See Computed tomography cancer and, 98, 435
Culture, 33, 301–302 clinical characteristics of, 103–106
Cushing’s syndrome, 366 core features, 103, 103
Cutaneous disorders. neuropsychiatric impairments
See Dermatological disorders on mental status
CVD. See Cardiovascular disease examination, 105–106,
Cyanocobalamin deficiency, 101, 135, 107
368 prodromal and subsyndromal
Cyclobenzaprine, for fibromyalgia, 380 states, 104
Cyclosporine, 472 psychomotor variations, 104
Cyproheptadine, for serotonin temporal course, 105, 106–107,
syndrome, 284 108
Cytarabine, 436 cocaine intoxication, 266–267
Cytochrome P450 (CYP) isoenzymes, consultation effectiveness in, 97
276–277 definition of, 97
drug interactions related to, dementia and, 99, 105
278–281, 406, 472–473 diagnosis of, 106–109
genetic variations in, 277, 303 components of diagnostic
assessment, 106–107
diagnostic instruments, 107,
Dalmane. See Flurazepam 109
Dantrolene, for neuroleptic malignant electroencephalogram, 107
syndrome, 289 differential diagnosis of, 85, 107,
DBS (deep brain stimulation), 295–296 108
Decubitus ulcers, 98 mania, 179
Deep brain stimulation (DBS), in disaster and terrorism casualties,
295–296 351, 353
Defense mechanisms, 64–65 in elderly persons, 98, 99, 103, 107
immature, 65 epidemiology of, 98–99
mature, 64–65 Hashimoto’s encephalopathy,
neurotic, 65 364–365
Dehydration, 99, 135, 151, 285, 291 HIV-associated, 403, 405–406
496 Clinical Manual of Psychosomatic Medicine

Delirium (continued) toxic etiologies, 100–101, 101

impact on health care costs, 99 predisposing factors for, 99
incidence of, 98 relationship to delirium etiology,
in intensive care unit, 98, 99 99, 100
management of, 110–116 risk factors, 99
environmental, 110–111 prevention of, 109
in HIV disease, 405–406 in serotonin syndrome, 283
identification and reversal of suicide and, 74
remediable etiologies, 110 after transplant surgery, 471
pharmacological, 26, 111–116 underrecognition of, 97
antipsychotic-associated Wernicke’s encephalopathy,
morbidity and mortality 253–254, 367
risks, 114 Delirium Rating Scale (DRS), 109
antipsychotic dosages, 112, Delirium tremens (DTs), 252, 253
113 Delusional psychocutaneous
evidence base for, 111–112 conditions, 339–341
frequently used clinical management of, 341
antipsychotics, clinical presentations of other forms
112–113 of, 341
haloperidol for hyperactive delusional parasitosis, 215, 339,
delirium, 113, 113 340–341
medication alternatives, Delusions, 33
115–116 during amphetamine intoxication,
practice guideline 263
recommendations, in delirium tremens, 253
114–115 in dementia, 108
symptom reduction, 110–113 Alzheimer’s disease, 123
in ventilator-dependent patients, in depression, 108
444 in disaster and terrorism casualties,
morbidity and mortality associated 353
with, 98 of infestation, 215, 339, 340–341
poststroke, 457 olfactory, 215
precipitating factors and etiologies somatic, 215
of, 100–102 Dementia, 119–141
central nervous system age-related prevalence of, 119, 121
conditions and events, 102 of Alzheimer’s type, 122–123,
hypoxic etiologies, 102 124–125
inflammatory etiologies, 102 antipsychotic-related mortality in
metabolic etiologies, 101 elderly persons with, 114, 139
 Index 497

clinical features of, 108, 120–121 cholinesterase inhibitors, 138,

cognitive decline and sufficient 141
impairment, 120 cognitive training, 137
memory impairment, 120 memantine, 138
multiple cognitive deficits, 120 other medications, 138
neurological disorders, 120–121 general management, 135–137
in Creutzfeldt-Jakob disease, for comorbid medical
130–131 conditions, 137
delirium and, 99, 105 decisions regarding life-
differential diagnosis of, 131, 132 prolonging interventions,
delirium, 108 137
depression, 108, 167, 168 for pain, 137
epidemiology of, 119–120 review of potential
evaluation of, 131–135 contributions, 135
hierarchical approach to, 133 in HIV disease, 406
history taking, 131, 134 nonpharmacological interventions
laboratory tests, 135, 136 for neuropsychiatric
mental status examination, symptoms, 138
134–135, 136 validation therapy, 138
neuroimaging, 135, 137 pharmacotherapy for agitation and
neuropsychological tests, 135, aggression, 139–141
136 anticonvulsants, 141
family history of, 121 antidepressants, 141
frontotemporal, 129–130, 130 atypical antipsychotics, 139–141
HIV-associated, 401, 402, 403, 406 cholinesterase inhibitors, 141
with Lewy bodies (DLB), 127, 128, typical antipsychotics, 139
204 Demoralization, 163, 165, 445
mild cognitive impairment and, 121 promoting resilience rather than
mortality and, 120 vulnerability, 308, 310–311
in Parkinson’s disease, 127 Denial, 66
poststroke, 457 Dependent personality disorder, 215
rapidly progressive, 130–131 Depression, 159–178
risk factors for, 121–122 bariatric surgery and, 322
vascular, 123, 125, 126 in bereaved caregivers, 437
Dementia antipsychotic withdrawal bipolar, 179
trial, 140–141 brain abnormalities and, 167
Dementia treatment, 135–141 clinical features of, 108
for cognitive deterioration, during cocaine withdrawal, 266
137–138 cognitive effects of, 167
498 Clinical Manual of Psychosomatic Medicine

Depression (continued) diagnosis of, 162–163

demoralization and, 163, 165 fibromyalgia, 379
diagnostic criteria for, 164–165 gastroesophageal reflux disease,
differential diagnosis of 386
body dysmorphic disorder, 231 head trauma, 454, 455
dementia, 108, 167, 168 hepatitis C virus infection, 393
normal grief, 163 HIV disease, 401, 404, 406–407
in disaster and terrorism casualties, idiopathic pulmonary fibrosis,
353–354 445
duration of, 160 inflammatory bowel disease, 390
in elderly persons, 160 irritable bowel syndrome, 389
fatigue in, 162, 374 medical outcomes and, 161–162
functional impairment in, 160 osteoporosis, 366
hypothalamic-pituitary-adrenal axis outcome of, 160
in, 332 pulmonary hypertension, 446
impact on medical utilization and sarcoidosis, 446
costs, 160 spinal cord injury, 461
inflammation and, 332 stroke, 457, 459
medical illness and, 159, 165, 166 thyroid disease, 363–364
asthma, 443–444 ventilator dependence, 445
cancer, 427–430 medication-induced, 166, 182, 391
cardiovascular disease, 161, 162, mortality and, 162
329–332 as neurodegenerative disorder, 167
comorbidity mechanisms, pain and, 433
331–332 platelet activity in, 331
prevalence of comorbidity, postpartum, 153, 412, 419
329 in pregnancy, 412–414
prognostic significance, medical comorbidity with, 414
330–331 preterm delivery and, 413
risk for onset of cardiovascular screening for, 414
disease, 330 treatment of, 414–418
treatment of depression and prevalence of, 159
reduction of psychiatric comorbidity with, 159
cardiovascular risk, Alzheimer’s disease, 123
334–335 anxiety disorders, 85
chronic obstructive pulmonary eating disorders, 148
disease, 442–443 hypochondriasis, 225
diabetes mellitus, 159, 162, opiate dependence, 260
360–363 pain disorder, 234
 Index 499

Parkinson’s disease, 127, 165 serotonin-norepinephrine

somatization disorder, 221 reuptake inhibitors,
suicidality, 70, 71, 74 170–171
risk factors for, 331 trazodone, 171
screening instruments for, 167–169 tricyclic antidepressants,
secondary to general medical 171–172
condition, 165, 166 for bipolar depression, 184,
sleep disturbances and, 163, 195 185–186
sociodemographic factors and, psychostimulants, 173–174, 174
160–161 in HIV disease, 407
somatic symptoms of, 162, 163, strategies and outcomes of,
214 175–177
speech in, 32 comparative efficacy and
Depression treatment, 169–178 tolerability among
in asthma, 444 new-generation
in cardiovascular disease, 334–335 antidepressants, 177
in chronic obstructive pulmonary depression severity associated
disease, 443 with antidepressant
deep brain stimulation, 295–296 effects, 177
in diabetes mellitus, 362–363 remission vs. response, 175
in disaster and terrorism casualties, STAR*D study, 175–177
354 postpartum, 419
electroconvulsive therapy, 178, in pregnancy, 414–419
294–295 electroconvulsive therapy, 418
in pregnancy, 418 general approach to, 415
noncompliance with, 161–162, pharmacological, 415–419, 416
163 preterm birth and, 413
pharmacological, 169–177 psychotherapy, 415
antidepressants, 169–173 relapse risk with antidepressant
augmentation of, 174, 176, discontinuation, 414
177, 364 psychological, 178
bupropion, 171 for bipolar depression, 186
in HIV disease, 406 in pregnancy, 415, 419
mirtazapine, 171 in stroke patients, 459
monoamine oxidase in thyroid disease, 364
inhibitors, 172–173 vagal nerve stimulation, 295
in pregnancy, 415–418, 416 in ventilator-dependent patients,
selective serotonin reuptake 445
inhibitors, 169–170 Dermatitis artefacta, 342–343
500 Clinical Manual of Psychosomatic Medicine

Dermatological disorders, 339–346 behavioral effects of, 360–361

delusional psychocutaneous consequences of, 361
disorders, 339–341 pathophysiology of, 360
delusional parasitosis, 340–341 postpartum, 414
with exacerbation by psychological treatment of, 362–363
factors, 345–346 eating disorders and, 152
acne, 345 medical complications of, 359–360
atopic dermatitis, 345–346 prevalence of, 359
psoriasis, 345 risk factors for, 291
factitious psychocutaneous sleep disturbances and, 196, 203,
disorders, 342–343 205
factitious dermatitis, 342–343 Dialectical behavior therapy, 408
psychogenic purpura, 343 Dialysis patients, 18, 72, 196
onychophagia, 344 antidepressant use in, 292
somatoform psychocutaneous lithium use in, 293
disorders, 341–342 Diazepam, 86, 88
body dysmorphic disorder, for alcohol withdrawal seizures, 252
341–342 for benzodiazepine withdrawal, 259
idiopathic pruritus, 342 Differential diagnosis, 7
trichotillomania, 343–344 Diffuse axonal injury, 453
Desvenlafaxine Digit span test, 37
for depression, 170 Digitalis, 82, 101
drug interactions with, 472 Dignity-conserving therapy, with
Detoxification cancer patients, 430
from alcohol, 249–250 Digoxin, 87
from opiates, 260 Diphenhydramine, 202, 386
Dexmedetomidine, for delirium, 116, Disaster and terrorism casualties,
444 349–357
Dextroamphetamine, for depression, clinical evaluation of, 350–351
173 advanced trauma life support,
in cancer, 430 350–351
in HIV disease, 407 early identification of psychiatric
Dextromethorphan/quinidine, for casualties, 351, 352–353
pseudobulbar affect, 460 symptom overlap, 350
Diabetes mellitus, 72, 122, 359–363, diagnosis and management of,
390, 393 351–357
antipsychotic-induced, 292 acute stress disorder and
bipolar disorder and, 179 posttraumatic stress
depression and, 159, 162, 360–363 disorder, 354–355, 355
 Index 501

delirium, 351, 353 “Doctor shopping,” 220, 341

depression, 353–354 Doctor–patient relationship, 8–9,
dissociation and dissociative 14–16
disorder, 356 adherence to psychotropic drug
effects of disaster medications, therapy and, 273, 406
357 confidentiality in, 8–9, 14–16
health anxiety and culture and, 302
hypochondriasis, 355 signing out against medical advice
substance use disorders, 357 and, 17
unexplained physical symptoms somatization and, 209
and conversion symptoms, with suicidal patient, 74
356 Documentation, 13.
Disclosure of patient information, 8–9, See also Medical records
14–15. of capacity, 22
See also Confidentiality of cognitive examination, 22
Disease vs. illness, 210 of communications with suicidal
Disinhibition, poststroke, 458 patient, 74
Disorientation of do-not-resuscitate and
alcohol intoxication and, 247 do-not-intubate orders, 19
delirium and, 37, 105, 108 malpractice and, 27
delirium tremens and, 253 of prescribing drugs for
dementia and, 108 nonapproved uses, 26
in HIV disease, 401 of psychotherapy completion before
Displacement, 66 bariatric surgery, 325
Dissociation and dissociative disorders, of seclusion and restraint, 25–26
in disaster and terrorism casualties, of signing out against medical
356 advice, 17–18
Distractibility, 37, 180 Domestic abuse or violence, 307
Distribution of drug, 274, 276 Donepezil, for dementia, 138
after bariatric surgery, 324, 326 Donor evaluation for organ
in heart failure, 469 transplantation, 469–470
Disulfiram, 101, 250–251 Doral. See Quazepam
Diuretics, 198 Doxepin
abuse of, 146, 151, 151 for atopic dermatitis, 346
Divorce, 70 for insomnia, 201
DLB. See Dementia, with Lewy bodies Droperidol, 285, 290
Do-not-intubate (DNI) order, 18–19 DRS (Delirium Rating Scale), 109
Do-not-resuscitate (DNR) order, Drug interactions, 277
18–19 with carbamazepine, 184
502 Clinical Manual of Psychosomatic Medicine

Drug interactions (continued) Dysarthria, 47

cytochrome P450-related, 278–281, Dysbulia, 47
406, 472–473 Dyscalculia, 47
with immunosuppressive Dysgnosia, 47
medications, 472–473 Dysgraphia, 47
with lithium, 183 Dyslexia, 47
with monoamine oxidase inhibitors, Dyslipidemia, 179
87, 173 antipsychotic-induced, 292
pharmacodynamic, 277 metabolic syndrome and, 291–292
pharmacokinetic, 277 Dyspepsia, 387
with selective serotonin reuptake Dysphagia, 386
inhibitors, 170, 406, 429, 435 Dysphasia, 47
with tamoxifen, 429, 435 Dysphonia, 32
DSM-5, 213 Dyspraxia, 47
DSM-IV-TR Dysprosody, 47, 458
anorexia nervosa in, 146 Dysthymic disorder
bulimia nervosa in, 146 hypochondriasis and, 225
cultural competence in, 302 somatization disorder and, 221
dementia of Alzheimer’s type in, Dystonia, 90
124–125
depression in, 162–163, 164–165, Eating disorder(s), 145–155
165 anorexia nervosa, 146
manic episode in, 180 assessment of, 148–149
somatization disorder in, 221 binge-eating disorder, 147
substance-related disorders in, 246 bulimia nervosa, 146
trichotillomania in, 343 chronic course of, 147
vascular dementia in, 126 diabetes mellitus and, 152
DTs (delirium tremens), 252, 253 diagnostic overlap among, 145
Dual diagnosis, 404 differential diagnosis of, 149, 150
Dual-energy X-ray absorptiometry, 149 body dysmorphic disorder, 231,
Duloxetine 232
for depression, 170–171, 177 medical complications of, 149–152,
in cancer, 430 151
in diabetes mellitus, 362 cardiac changes, 150
drug interactions with, 429 electrolyte imbalances and
for fibromyalgia, 380 nutritional deficiencies,
for generalized anxiety disorder, 87 151–152
Durable power of attorney, 13, 19–20, endocrine changes, 150–151
23 osteopenia, 150
 Index 503

mortality and, 148 Educational interventions.

night eating syndrome, 147 See Psychoeducation
not otherwise specified, 146–147, EEG (electroencephalogram)
148 in delirium, 107
pathogenesis of, 148 in sleep, 195, 196
pregnancy and, 152–153 Elderly persons
prevalence of, 147 cognitive impairment in, 36
psychiatric comorbidity with, 148 delirium in, 99
treatment of, 153–155 etiologies of, 107
anorexia nervosa, 153–154 mortality associated with, 98
bariatric surgery, 155, 319–327 screening inpatients for, 103
binge-eating disorder, 155 dementia in, 119, 121
bulimia nervosa, 154 –155 Alzheimer’s disease, 122
Eating patterns depression in, 160
of bariatric surgery candidates, 324, drug absorption in, 274
325 drug metabolism in, 274, 276
in frontotemporal dementia, 129 factitious disorder by proxy in,
Eaton, James, 3 236
Ebstein’s anomaly, 420 insomnia in, 198
ECG. See Electrocardiogram psychotropic drug therapy for
Echolalia, 32 antipsychotic-related mortality,
Economic issues 114, 139, 140–141
billing, 6 benzodiazepines, 86, 200, 432
cost-effectiveness of psychosomatic lithium, 183
medicine, 6 monoamine oxidase inhibitors,
costs of chronic obstructive 172
pulmonary disease, 441 psychostimulants, 173
financial worries of patients, 306 renal drug excretion in, 277
impact of psychiatric disorders on suicide among, 70
health care costs, 6 Electrocardiogram (ECG)
delirium, 99 for antipsychotic use in delirium,
maintaining financial viability of 114–115
psychosomatic medicine for lithium use, 183
services, 6 for tricyclic antidepressant use,
reimbursement for services, 4, 7, 11 172
Ecstasy (3,4-methylenedioxymeth- Electroconvulsive therapy (ECT),
amphetamine), 264 294–295
ECT. See Electroconvulsive therapy cardiac complications of, 295
Edinburgh Depression Scale, 414 for catatonia, 178
504 Clinical Manual of Psychosomatic Medicine

Electroconvulsive therapy (ECT) End-organ failure, 468–469.

(continued) See also Transplantation
for depression, 178, 294 End-stage renal disease (ESRD).
in chronic obstructive pulmonary See Renal disease/failure
disease, 443 Endocrine disorders, 79, 82, 359–369
for neuroleptic malignant adrenal gland disorders, 366
syndrome, 289 delirium due to, 101
precautions for use of, 294–295 diabetes mellitus, 359–363
in pregnancy, 418 eating disorders and, 150–151
Electroencephalogram (EEG) indications for endocrine
in delirium, 107 assessment, 368–369
in sleep, 195, 196 osteoporosis, 366–367
Electrolyte imbalances parathyroid disorders, 365–366
during alcohol withdrawal, 249, 253 pheochromocytoma, 367
delirium due to, 101 thyroid disease, 363–365
in eating disorders, 151–152 vitamin deficiencies, 367–368
QTc interval prolongation and, 150 Enhancing Recovery in Coronary Heart
in refeeding syndrome, 154 Disease (ENRICHD) study, 335
Elimination of drug, 277, 468–469 Environmental interventions, for
Emergencies delirium, 110–111
do-not-resuscitate and do-not- Ephedrine, 82, 101
intubate orders in, 18–19 Epidural hematoma, 453
informed consent in, 16 Epilepsy, 82, 83, 159, 181, 227, 414.
suicidality, 69–75 See also Seizures
Emergency department, management Epinephrine, 82, 101, 357
of suicidality in, 75 Epworth Sleepiness Scale, 197
Encephalitis, 82, 102 Escitalopram, 170
limbic, 102 for depression, 177
Encephalopathy drug interactions with, 472
Hashimoto’s, 364–365 in pregnancy, 417
hepatic, 294, 393–394, 469 for stroke patients, 460
in HIV disease, 403 ESRD (end-stage renal disease).
hyperammonemic, 294, 394, 469 See Renal disease/failure
hypertensive, 102 Estazolam, 88
Wernicke’s, 253–254, 367 Estrogen, 150, 151
End-of-life care Estrogen therapy, 435
in cancer, 435–437 Eszopiclone, for insomnia, 201
in pulmonary hypertension, Ethnicity/race, 302–303
446–447 dementia and, 121
 Index 505

differential diagnosis and, 302–303 Exposure therapy, 91

HIV disease and, 400 for specific phobias, 92
psychopharmacology and, 303
genomics, 303 Factitious disorders, 212, 221, 235–237
herbal and alternative clinical course and prognosis for, 237
preparations, 303 clinical features of, 235–236
suicide and, 70 differential diagnosis of, 236
Euthyroid sick syndrome, 151 malingering, 238
Excessive daytime sleepiness, 196, 202 epidemiology of, 235
Executive function deficits. levels of, 236
See also Cognitive impairment/ management of, 237
decline by proxy, 236
in delirium, 106 psychocutaneous, 339, 342–343
in dementia, 120 factitious dermatitis, 342–343
Alzheimer’s disease, 123 psychogenic purpura, 343
frontotemporal dementia, 130 Family/significant others
vascular dementia, 125 asking to leave room during
poststroke, 458 cognitive examination, 36
thyroid disease and, 363 guardianship by, 23–24
Executive function tests, 44–46. obtaining patient permission to
See also Cognitive assessment speak with, 15
cognitive estimates, 45 reversal of do-not-resuscitate or do-
go–no go evaluation of impulsivity, not-intubate orders by, 18–19
45 Family therapy, 313
letter and category fluency, 44 for anorexia nervosa, 154
Luria three-step test, 45–46 Fatigue, 373–377
similarities, 45 cancer-related, 433–434, 434
Exercise chronic, 375–377 (See also Chronic
compulsive, 151 fatigue syndrome)
for fibromyalgia, 381 premorbid predictors of, 374
graded, in chronic fatigue syndrome, definition of, 373
377 differential diagnosis of, 374, 375
in somatoform disorders, 219 epidemiology of, 373–374
Existential factors, 305–306 hepatitis C virus infection and, 393
Existential therapy, for depression in HIV disease and, 404
cancer, 430 neurasthenia, 374
Exposure and response prevention, for poststroke, 459, 460
obsessive-compulsive disorder, psychiatric comorbidity with, 374
92 depression, 162
506 Clinical Manual of Psychosomatic Medicine

Fibromyalgia syndrome (FMS), Fluphenazine, for delusional parasitosis,

170.171, 196, 378–381 340
classification criteria for, 378 Flurazepam, 88
clinical features of, 378–379 Fluvoxamine
epidemiology of, 378 for depression, 177
irritable bowel syndrome and, drug interactions with, 170, 472
388 for posttraumatic stress disorder,
pathophysiology of, 378 355
psychiatric comorbidity with, 379 FMS. See Fibromyalgia syndrome
somatization, 379 Folate deficiency, 101, 368
treatment of, 380–381 Follicle-stimulating hormone, 151
Fiorinal. See Butalbital Frank Jones story test, 42
Flight of ideas, 33, 180 Frontal lobes, 81
Floppy infant syndrome, 418, 420 Frontotemporal dementia,
Fluency, 38 129–130
Flumazenil, for benzodiazepine clinical features of, 129–130
overdose, 258 diagnostic criteria for, 130
5-Fluorouracil, 436 pathophysiology of, 129
Fluoxetine prevalence of, 129
active metabolite and elimination
half-life of, 170 GABA (γ-aminobutyric acid), in
for bulimia nervosa, 155 anxiety, 80
for cataplexy, 203 Gabapentin
for depression, 177 for anxiety in chronic obstructive
in HIV disease, 406 pulmonary disease, 442
interferon-induced, 429 in bipolar disorder, 185
in pregnancy and breast-feeding, for fibromyalgia, 380–381
417, 419 for hot flashes in cancer patients,
drug interactions with, 170, 429, 435
435, 472 for periodic limb movement
in liver disease, 293 disorder, 205
for obsessive-compulsive disorder, in renal disease, 469
92 GAD. See Generalized anxiety disorder
for panic disorder, 91 Galantamine, for dementia, 138
for posttraumatic stress disorder, Ganciclovir, 101
355 Gastric banding, adjustable, 319.
in renal disease, 292 See also Bariatric surgery
switching from monoamine oxidase Gastroesophageal reflux disease
inhibitor to, 173 (GERD), 196, 385
 Index 507

Gastrointestinal disorders, 385–394 Generalized anxiety disorder (GAD), 82

anticipatory nausea/vomiting, 387 bariatric surgery and, 322
brain-gut axis and, 385 chronic obstructive pulmonary
drug-induced bleeding, 392 disease and, 442
dyspepsia and peptic ulcer disease, head trauma and, 454
385, 387 hypochondriasis and, 225
dysphagia, 385 pharmacotherapy for, 86–90
gastroesophageal reflux disease, 196, antidepressants, 87
385 antipsychotics, 90
globus hystericus, 385 benzodiazepines, 86–87, 88–89
hyperemesis gravidarum, 152, 387, beta-blockers, 90
417, 421–422 buspirone, 87
inflammatory bowel disease, 389–392 postpartum, 412
irritable bowel syndrome, 385, psychotherapy for, 90–91
388–389 behavior therapy, 91
noncardiac chest pain, 387 cognitive-behavioral therapy,
Gastroplasty, vertical-banded, 319. 90
See also Bariatric surgery psychodynamic psychotherapy,
Gemcitabine, 436 90
Gender supportive psychotherapy, 90
alcohol abuse and, 247 Genetic factors
anxiety disorders and, 80 in Alzheimer’s disease, 122
cardiovascular disease and, 329 in eating disorders, 148
chronic obstructive pulmonary in frontotemporal dementia, 129
disease and, 441 polymorphisms of cytochrome
conversion disorder and, 226 P450 isoenzymes, 277, 303
depression and, 159, 160 shared, in fibromyalgia and
eating disorders and, 147 depression, 379
factitious disorders and, 235 Genomics, 303
fatigue and, 373–374 GERD (gastroesophageal reflux
chronic fatigue syndrome, 376 disease), 196, 385
fibromyalgia and, 378 Globus hystericus, 386
HIV disease and, 400 γ-Glutamyltransferase, 256
insomnia and, 198 Gonadotropin-releasing hormone, 151
personality disorders and, 215 Go–no go test, 45
restless legs syndrome and, 205 Graded exposure
somatization disorder and, 221 for obsessive-compulsive disorder,
spinal cord injury and, 460 92
suicidality and, 70, 71 for specific phobias, 92
508 Clinical Manual of Psychosomatic Medicine

Grandiosity, 180 in delirium tremens, 253

Grief, vs. depression, 163 in dementia, 108
Group psychotherapy, 312 Alzheimer’s disease, 123
with cancer patients, 430 dementia with Lewy bodies, 127
for depression, 178 in depression, 108
postpartum, 419 in disaster and terrorism casualties,
for somatoform disorders, 220 353
Groups, psychoeducational, 309, 311 gustatory, 34
Growth hormone, 151 hypnagogic, 203
Guardianship, 14, 19, 23–24 kinesthetic, 34
choice of guardian, 23–24 olfactory, 34
legal establishment of substitute tactile, 34
decision maker, 23 visual, 33
specific vs. general, 23 Hallucinogens, 82
standard of proof for incompetency, Haloperidol
23 for agitation and aggression in
dementia, 139
HAART. See Highly active antiretroviral for alcohol-induced psychotic
therapy for HIV/AIDS disorder, 252
Habit reversal training for alcohol intoxication, 248
for atopic dermatitis, 346 for anxiety in medical settings, 90
for idiopathic pruritus, 342 cardiac effects of, 112, 115, 290–291
for onychophagia, 344 for delirium, 111–113
for trichotillomania, 344 dosage and administration of,
HADS (Hospital Anxiety and 112, 113, 113
Depression Scale), 168 vs. lorazepam, 111–112
Hair pulling, 343–344 for delusional parasitosis, 340
Halcion. See Triazolam with lithium for mania, 183
Half-life of drug, 276 in liver disease, 294
benzodiazepines, 86, 201 for panic disorder, 91
selective serotonin reuptake in pregnancy, 422
inhibitors, 170 for sedative-hypnotic intoxication,
Hallucinations, 33–34, 37 258
alcohol-withdrawal, 249 Hamilton Rating Scale for Depression
during amphetamine intoxication, (Ham-D17), 175
263 Hashimoto’s encephalopathy, 364–365
auditory, 33 HCV (hepatitis C virus) infection,
in delirium, 106, 108 392–393
 Index 509

Head trauma. Highly active antiretroviral therapy

See Traumatic brain injury (HAART) for HIV/AIDS, 401
Headache, vascular, 82 antidepressant interactions with,
Health anxiety, 84–85 406
in disaster and terrorism casualties, HIV-associated dementia and, 403,
355 406
treatment of, 93 neuropsychiatric effects of, 402
Health care costs, impact of psychiatric substance abuse and adherence to,
disorders on, 6 404
anxiety, 79–80 HIPAA (Health Insurance Portability
delirium, 97, 99 and Accountability Act), 9, 14–15
delusional parasitosis, 340 Hippocampus, 81
dementia, 119 Histrionic personality disorder, 215,
depression, 160 221
diabetes mellitus and, 361 HIV. See Human immunodeficiency
pain disorder, 234 virus disease
somatization disorder, 213, 222 Homicidality, 35
Health care proxy, 13, 19–20 Hopelessness, 308
Health Insurance Portability and Hormone replacement therapy, 138
Accountability Act (HIPAA), 9, Hospital Anxiety and Depression Scale
14–15 (HADS), 168
Hearing impairment, 99, 135 Hospitalization, psychiatric
Heart transplantation, 468, 469, 473 for alcohol withdrawal, 249
Heatstroke, 102 for anorexia nervosa, 153
Helicobacter pylori infection, 385, 387 involuntary, 24–25
Hemoglobin A1c, 360, 362 for postpartum psychosis, 413
Hepatic drug metabolism, 276, 469 of suicidal patient, 73
first-pass, 274 Hot flashes in cancer patients, 169,
phase I and phase II, 276 170, 435
Hepatic encephalopathy, 294, HPA (hypothalamic-pituitary-adrenal)
393–394, 469 axis
Hepatitis B virus infection, 393 in cancer-related fatigue, 433
Hepatitis C virus (HCV) infection, in depression and cardiovascular
392–393 disease, 332
Hepatocellular carcinoma, 392, 393 Human immunodeficiency virus (HIV)
Herbal and alternative preparations, disease, 72, 102, 159, 181, 196,
303 374, 399–408
Herpes simplex infection, 402 epidemiology of, 399–400
510 Clinical Manual of Psychosomatic Medicine

Human immunodeficiency virus (HIV) Hypercholesterolemia, 122

disease (continued) Hyperemesis gravidarum, 152, 387
highly active antiretroviral therapy antipsychotics for, 421–422
for, 401 mirtazapine for, 417
neuropsychiatric syndromes in, Hyperglycemia, 101, 152, 179, 361.
401–402 See also Diabetes mellitus
aggressive management of, 402 metabolic syndrome and, 291
causes of, 401 Hyperkalemia, 82, 101, 152
in HIV infection without AIDS, Hyperkinetic delirium, 104
402 pharmacological management of,
medication-induced, 402 111–116
mental status changes, 402 Hyperlipidemia, 122, 137
psychiatric disorders in, 403–408 Hyperparathyroidism, 365
anxiety disorders, 404–405, 408 Hyperprolactinemia, 367
delirium, 403, 405–406 Hypersomnias of central origin, 203
depression, 404, 406–407 Hypertension, 122, 137, 179, 210
HIV-associated dementia, 403, gestational, 415
406 metabolic syndrome and, 291
mania, 404, 407 pulmonary, 446–447
personality disorders, 405, 408 venlafaxine-induced, 170
substance use disorders, 404, Hypertensive crisis, monoamine
407–408 oxidase inhibitor–induced, 173
treatment of, 405–408 Hypertensive encephalopathy, 102
survival after AIDS diagnosis, 401 Hyperthermia, 82
time to progression to AIDS, 400 in anticholinergic delirium, 286
transmission of, 400, 405 malignant, 286–287, 288
tuberculosis and, 447 in neuroleptic malignant syndrome,
Humor, 65 286, 287
Huntington’s disease, 82 in serotonin syndrome, 284, 286
HVS (hyperventilation syndrome), Hyperthyroidism, 82, 101
447 Hyperventilation syndrome (HVS),
Hydrocephalus, 102 447
Hydrophilic drugs, 274, 276 Hypnosis, 91, 313
γ-Hydroxybutyrate, for cataplexy, 203 for psoriasis, 345
Hydroxyzine, for anxiety, 432, 442 in somatoform disorders, 220
Hyperadrenalism, 82, 101 Hypoalbuminemia, 469
Hyperammonemic encephalopathy, Hypocalcemia, 82, 150, 152, 154
294, 394, 469 Hypochondriacal psychosis,
Hypercalcemia, 365 monosymptomatic, 215
 Index 511

Hypochondriasis, 214, 224–226 ICU (intensive care unit)

clinical course and prognosis for, circadian rhythm sleep disorders in,
225 203
clinical features of, 224 delirium in, 98, 99
differential diagnosis of, 225 Ideas of reference, 33
malingering, 238 Identity, cultural, 302
in disaster and terrorism casualties, Idiopathic pulmonary fibrosis, 445
355 Ifosfamide, 436
epidemiology of, 224 Illusions, 33
management of, 225–226, 355 alcohol-withdrawal, 249
psychiatric comorbidity with, 225 in delirium, 106
Hypoglycemia, 101, 154, 236, 249 Iloprost, for pulmonary hypertension,
Hypokalemia, 101, 150, 151–152, 154, 446
249 Imagery-based exposure, for specific
Hypokinetic delirium, 104, 105, phobias, 92
111 Immunosuppressive medications
Hypomagnesemia, 150, 152, 154, 249, interaction with antidepressants,
253 472–473
Hypomania, 182 neuropsychiatric effects of, 472,
Hyponatremia, 82, 101, 152, 170, 249 473–474
Hypoparathyroidism, 82, 365–366 Implantable cardioverter-defibrillator,
Hypophosphatemia, 152, 154, 249 333–334
Hypotension, orthostatic, 291 Impulse-control disorders
Hypothalamic-pituitary-adrenal (HPA) depression and, 159
axis trichotillomania, 339, 343–344
in cancer-related fatigue, 433 Impulsivity, 53, 61–62
in depression and cardiovascular eating disorders and, 148
disease, 332 go–no go test of, 45
Hypothalamus, 81 Incapacity, 20, 307.
Hypothyroidism, 101, 135, 165, See also Capacity
363–364 Incompetency, 14
lithium-induced, 292 determination of, 20
Hypoventilation syndromes, sleep- do-not-resuscitate or do-not-
related, 202 intubate orders and,
Hypovolemia, 81 18–19
Hypoxia, 102 guardianship for, 23–24
informed consent and, 16
IBD. See Inflammatory bowel disease standard of proof for, 23
IBS. See Irritable bowel syndrome Infanticide, 413
512 Clinical Manual of Psychosomatic Medicine

Infection(s) loss of, in frontotemporal dementia,

central nervous system, 102 129
Helicobacter pylori, 385, 387 Insomnia, 197–202
hepatitis C virus, 392–393 alcohol-related, 198, 250
HIV/AIDS, 399–408 causes of, 198, 199
Infertility, 152 definition of, 197–198
Inflammation, 102 epidemiology of, 198
atopic dermatitis and, 345–346 medical illness and, 196
depression, cardiovascular disease treatment of, 198–202
and, 332 nonpharmacological, 198, 200
Inflammatory bowel disease (IBD), sleep hygiene, 198, 199
389–392 pharmacological, 200–202,
anxiety, depression and, 390–391 201
epidemiology of, 390 benzodiazepines, 200
management of, 391–392 nonbenzodiazepine
psychiatric sequelae of treatment hypnotics, 200
for, 391 other medications, 201–202
Infliximab, for inflammatory bowel ramelteon, 200
disease, 391 Insulin therapy, 82, 152
Informed consent, 14, 16 Integrated care, 4, 5, 10–11
for bariatric surgery, 321 in primary care settings, 10
capacity to give, 21 in specialty care settings, 10–11
definition of informed patient, 16 Intensive care unit (ICU)
exceptions to requirement for, 16–17 circadian rhythm sleep disorders in,
emergencies, 16 203
incompetency, 16 delirium in, 98, 99
therapeutic privilege, 16–17 Interferon, 101, 436
waiver, 17 depression induced by, 429
factitious disorders and, 237 for hepatitis B virus infection, 393
for medication use during breast- mania induced by, 432
feeding, 416 Interleukin-2, 436
when prescribing drugs for Interpersonal psychotherapy (IPT), 312
nonapproved uses, 26 for depression
Injection drug use in cardiovascular disease, 335
hepatitis C virus infection and, postpartum, 419
392–393 for eating disorders, 154–155
HIV disease and, 400 for irritable bowel syndrome, 389
Insight Interpreter services, 304–305
assessment of, 35 Interstitial cystitis, 388
 Index 513

Interviewing medical conditions associated with,

about spiritual, existential, and 388
religious beliefs, 305–306 psychiatric issues in, 388–389
to evaluate capacity, 22 Isolation of affect, 66
for evaluation of somatoform Isoniazid, 101, 447
disorders, 216–217
language barriers and, 303 Jehovah’s Witnesses, 16
use of interpreters for, Jet lag, 203
304–305 Judgment, assessment of, 35
listening and observing during, 8
mental status examination, 22, Kernig’s sign, 46
31–47 Kidney transplantation, 467–469
structured vs. unstructured style for, evaluating donors for, 470
8 Klonopin. See Clonazepam
Intoxication, 32 Korsakoff syndrome, 152, 250,
alcohol, 247–248 253–254
barbiturate, 257
cocaine, 265–267 Laboratory testing
in disaster and terrorism casualties, in alcoholism, 256–257
357 for antipsychotic use, 292
vs. neuroleptic malignant syndrome, for cocaine, 264–265
289 in delirium, 107
opiate, 260–261 in dementia, 135, 136
sedative-hypnotic, 258 in eating disorders, 149
Introversion, 376 for lithium use, 183
Involuntary hospitalization, 24–25 in neuroleptic malignant syndrome,
commitment laws and, 25 288
legal commitment, 24 for pheochromocytoma, 367
role of consulting psychiatrist in, in serotonin syndrome, 284
24–25 in sleep evaluation, 197
substantive criteria for statutory Lamotrigine
commitment, 24 adverse effects of, 184–185
IPT. See Interpersonal psychotherapy for bipolar depression,
Iron deficiency, 205 184–185
Irritable bowel syndrome (IBS), 385, during pregnancy and breast-
388–389 feeding, 421
clinical features of, 388 Language
epidemiology of, 388 assessment of, 38
management of, 389 impairments of, in delirium, 106
514 Clinical Manual of Psychosomatic Medicine

Language barriers, 303 dosage and monitoring of, 183

use of interpreters for, 304–305 drug interactions with, 183
Laxative abuse, 146, 151, 151, 152 for elderly persons, 183
Lead poisoning, 101 for mania, 182–184
Left ventricular assist device (LVAD), antipsychotics and, 183
81, 334 corticosteroid-induced, 432
Legal issues. See Medicolegal issues in HIV disease, 407
Level of consciousness neuroleptic malignant syndrome
assessment of, 37 and, 285
in delirium, 105 during pregnancy and breast-
in neuroleptic malignant syndrome, feeding, 420
287 in renal disease, 293, 469
Levodopa, 82, 101, 198, 460. for suicide prevention, 182–183
See also Carbidopa-levodopa in traumatic brain injury, 456
Lewy bodies, dementia with, 127, 128, Liver disease/failure, 101, 102
204 alcoholic, 249, 250
Librium. See Chlordiazepoxide bariatric surgery and, 321
Lidocaine, 82, 101 drug-induced, 394
Life narrative, with cancer patients, 430 hepatic encephalopathy, 294,
Life-prolonging interventions, in 393–394, 469
dementia, 137 hepatitis B virus infection, 393
Light therapy, for circadian rhythm hepatitis C virus infection, 392–393
sleep disorders, 203 psychotropic drug use in, 293–294,
Limbic encephalitis, 102 469
Liothyronine, for depression, 174 antidepressants, 293
Lipophilic drugs, 274, 276, 326 antipsychotics, 294
Liquid drugs, 274 benzodiazepines, 294
Listening, 8 mood stabilizers, 294
Lithium, 182–184 Liver effects of drugs, 394
adverse effects and toxicity of, carbamazepine, 294
183–184 disulfiram, 251
delirium, 101 naltrexone, 251
Ebstein’s anomaly, 420 valproate, 184, 294
in neonates, 420 Liver transplantation, 467, 468, 469
psoriasis, 345 alcohol use after, 473
thyroid dysfunction, 292 evaluating donors for, 470
for antidepressant augmentation, Living will, 13, 19, 20, 23
174 Locus coeruleus, 81
in STAR*D study, 176 Loose associations, 33
 Index 515

Lorazepam, 86, 88 Malignant hyperthermia, 284,

for alcohol intoxication, 248 286–287, 288
for alcohol withdrawal, 249 Malignant melanoma, 429, 430
for amphetamine intoxication, 263 Malingering, 221, 237–239
for anxiety clinical features of, 237–238
in cancer, 432 course and prognosis for, 238
in chronic obstructive differential diagnosis of, 238
pulmonary disease, 442 epidemiology of, 237
for cocaine intoxication, 265, management of, 238–239
266–267 neurological examination in, 46–47
for delirium, 111, 115 secondary gain in, 237
vs. haloperidol, 111–112 Malpractice, 27
for insomnia, 201 Mania. See also Bipolar disorder
in liver disease, 294 in cancer, 432
for neuroleptic malignant diagnostic criteria for, 180
syndrome, 289 drug-induced
Loss antidepressants, 185
medical diagnosis and, 163 corticosteroids, 182, 391, 432
suicide as response to, 70, 71, 72 in HIV disease, 404, 407
Luria three-step test, 45–46 screening for, 179
Luteinizing hormone, 151 secondary, 180–182
LVD (left ventricular assist device), 81, etiologies of, 181, 181–182
334 vs. primary mania, 180
Lymphocytic colitis, 389 substance-induced, 181, 182
Lymphoma, central nervous system, 402 in traumatic brain injury, 456
treatment of, 182–185
Magnetic resonance imaging (MRI) anticonvulsants, 184–185
claustrophobia and, 83, 431 antipsychotics, 185
in dementia, 135, 137 in HIV disease, 407
HIV-associated, 403 lithium, 182–184
vascular dementia, 125 MAO (monoamine oxidase), 173
diffuse axonal injury on, 453 MAOIs. See Monoamine oxidase
in eating disorders, 149 inhibitors
Maintenance of Wakefulness Test Marie Three Paper Test, 43
(MWT), 197 Marital status, suicide and, 70
Major depressive disorder (MDD). Marital therapy, for posttraumatic stress
See Depression disorder, 355
Male feminization, 250 MAST (Michigan Alcohol Screening
Malignant catatonia, 288, 289 Test), 255
516 Clinical Manual of Psychosomatic Medicine

MDAS (Memorial Delirium pharmacokinetics of psychotropic

Assessment Scale), 109 drugs in, 274–277
MDD (major depressive disorder). pulmonary conditions, 441–448
See Depression self-production of (See Factitious
MDMA (3,4-methylenedioxymeth- disorders)
amphetamine, ecstasy), 264 sleep disorders and, 196, 198,
Medicaid, 19 199
Medical illness. vs. somatoform disorders, 214
See also specific medical conditions suicide and, 70, 71, 72, 163
alcohol-related, 250–251 undetected or underestimated, 238
anxiety disorders and, 79, 80, 81, 86 Medical records.
bariatric surgery and, 321 See also Documentation
bipolar disorder and, 179 do-not-resuscitate and do-not-
cancer, 427–437 intubate orders in, 19
cardiovascular disease, 329–335 malpractice and, 27
vs. conversion symptoms, 227–228 sharing of, 8–9
defenses to cope with, 64–65 HIPAA and, 9, 14–15
delirium and, 98 Medical staff
demoralization and, 165 attitudes about persons with
depression and, 159, 165, 166 substance-related disorders,
dermatological disorders, 339–346 245
vs. disease, 210 common responses to patient
eating disorders and, 149–152, 151 personality patterns, 55–64
endocrine disorders, 359–369 cold, deceitful patients, 63
fatigue and fibromyalgia, 373–381 dependent, demanding patients,
fear of, 224–225 55
(See also Hypochondriasis) dramatizing, emotional patients,
feigned (See Malingering) 57
gastrointestinal disorders, 385–394 guarded, suspicious patients, 59
hepatitis C virus infection, 392–393 idealizing, provocative patients,
HIV/AIDS, 399–408 62
irritable bowel syndrome and, 388 impulsive, acting-out patients,
patient factors affecting response to, 61–62
51–54 long-suffering, complaining
meaning of illness, 54 patients, 58
nature of the disease, 52–53 orderly, controlling patients, 56
personality and past history, seclusive, aloof patients, 61
53–54 superior, critical patients, 60
(See also Personality) timid, apprehensive patients, 64
 Index 517

Medically unexplained symptoms, signing out against medical

211–212. advice, 17–18
See also Somatoform disorder(s) seclusion and restraint, 25–26
in disaster and terrorism casualties, Meditation, 91, 220, 345
356 Megestrol acetate, 435
Medicare, 4, 19, 361 Melatonin, 201, 202, 203
Medications. See also Psychotropic drug Melatonin agonists, for insomnia, 200,
therapy; specific drugs and classes 201
anxiety induced by, 82 Memantine, for dementia, 138
delirium induced by, 100, 101 Memorial Delirium Assessment Scale
depression induced by, 166, 182 (MDAS), 109
dysphagia induced by, 386 Memory impairment
effects on patient’s experience and in delirium, 105, 108
behavior, 53 in dementia, 108, 120, 131
insomnia induced by, 198 Alzheimer’s disease, 122
intentional overdose of, 71 in HIV disease, 401
mania induced by, 181, 182 in Korsakoff syndrome, 253–254
off-label use of, 26 poststroke, 458
parasomnias induced by, 204–205 sedative-, hypnotic-, or anxiolytic-
sleep-related movement disorders induced persisting amnestic
induced by, 205 disorder, 259
Medicolegal issues, 13–27 thyroid disease and, 363
capacity, 20–23 Memory tests, 37, 38
confidentiality, 8–9, 14–16 Meningitis, 102
definitions related to, 13–14 Menopause, 196
factitious disorder and, 237 Mental status alterations, 37.
guardianship, 23–24 See also Cognitive impairment/
informed consent, 16–17 decline
involuntary hospitalization, 24–25 in anticholinergic delirium, 287
malingering and, 237–239 in HIV disease, 402
malpractice, 27 in malignant hyperthermia, 287
prescribing medications for in neuroleptic malignant syndrome,
nonapproved uses, 26 287, 287
right to direct medical treatment, in refeeding syndrome, 154
17–20 in serotonin syndrome, 283, 287
advance directives, 13–14, 19–20 Mental status examination (MSE), 22,
do-not-resuscitate and do-not- 31–47.
intubate orders, 18–19 See also Cognitive assessment
power of attorney, 19–20 in anxiety disorders, 85
518 Clinical Manual of Psychosomatic Medicine

Mental status examination (MSE) Methadone, 261

(continued) Methamphetamine, 412
for bariatric surgery evaluation, 324 Methotrexate, 101, 436
bedside screening tools for, 39–40 Methyldopa, 101
cognitive elements of, 36–39 3,4-Methylenedioxymethamphetamine
abstraction, 38–39 (MDMA, ecstasy), 264
attention, 37 Methylphenidate, 82
general considerations, 36–37 for cancer-related fatigue, 434
language, 38 in chronic fatigue syndrome, 377
level of consciousness and for depression, 173
orientation, 37 in cancer, 430
memory, 38 in HIV disease, 407
in delirium, 105–106, 107 in ventilator-dependent patients,
in dementia, 134–135, 136 445
of disaster and terrorism casualties, for narcolepsy, 203
352–353 in renal disease, 469
noncognitive elements of, 31–35 in traumatic brain injury, 456
affect, 34–35 Metoclopramide, 285
general appearance and behavior, Metrizamide, 101
31–32 Mexiletine, 101
insight and judgment, 35 MI. See Myocardial infarction
mood, 34 Michigan Alcohol Screening Test
speech, 32 (MAST), 255
suicidality and homicidality, 35 Microscopic colitis, 389
thought content, 33–34 Midazolam, 86, 88, 115
thought process, 33 Mild cognitive impairment (MCI),
Meperidine, 101, 260 120
Mercury poisoning, 101 hierarchical approach to diagnosis
Metabolic disorders, 82, 101 of, 133
Metabolic syndrome, 291–292 with at least one cognitive domain
antipsychotic-induced, 141, affected, 120
291–292, 340 prevalence and incidence of, 121
binge-eating disorder and, 152 risk of progression to dementia,
risk factors for, 291 121
Metabolism of drug, 276–277 without functional decline, 120
cytochrome P450 enzymes and, Milnacipran
276–277 for depression, 171
genetic variations in, 277, 303 in diabetes mellitus, 362
hepatic, 276, 469 for fibromyalgia, 380
 Index 519

MIND-IT (Myocardial INfarction and for depression, 172–173

Depression-Intervention Trial), 335 in STAR*D study, 176
Mini-Mental State Examination dietary restrictions with, 172, 173
(MMSE), 22, 40, 134, 136, 363 drug interactions with, 87, 173
modified, 134 for elderly persons, 172
Minnesota Multiphasic Personality mechanism of action of, 173
Inventory (MMPI), 217 oral and transdermal preparations
Mirtazapine of, 173
adverse effects of, 171, 392 for panic disorder, 91
for depression, 171, 174, 177 switching to another antidepressant
in cancer, 429–430 from, 173
in diabetes mellitus, 362 Monosymptomatic hypochondriacal
interferon-induced, 429 psychosis, 215
poststroke, 459 Montreal Cognitive Assessment
in STAR*D study, 176 (MoCA), 40, 134–135, 136
for hyperemesis gravidarum, 417 Mood, assessment of, 34
for inflammatory bowel disease, 392 Mood disorders, 159–186
for insomnia, 201 bipolar disorder and secondary
in pregnancy, 417 mania, 178–186
in renal disease, 292 body dysmorphic disorder and,
MMPI (Minnesota Multiphasic 231
Personality Inventory), 217 depression, 159–178
MMSE (Mini-Mental State head trauma and, 454, 455
Examination), 22, 40, 134, 136, HIV disease and, 404
363 in pregnancy, 412
modified, 134 somatic symptoms of, 214
MoCA (Montreal Cognitive suicide and, 70, 71, 74
Assessment), 40, 134–135, 136 Mood stabilizers, 182–185
Modafinil anticonvulsants, 184–185
for bipolar depression, 186 antidepressants and, 185
in chronic fatigue syndrome, 377 antipsychotics and, 185
for depression in cancer, 430 in HIV disease, 407
for narcolepsy, 203 lithium, 182–184
for poststroke fatigue, 460 in liver disease, 294
Monoamine oxidase (MAO), 173 during pregnancy and breast-feeding,
Monoamine oxidase inhibitors 420–421
(MAOIs), 172–173 in renal disease, 293
adverse effects of, 172 in traumatic brain injury, 456
orthostatic hypotension, 291 Morphine, 357
520 Clinical Manual of Psychosomatic Medicine

Mortality Myocardial INfarction and

alcohol-related, 247, 254 Depression–Intervention Trial
antipsychotic-related, 114, 139, (MIND-IT), 335
140–141, 290–291 Myocarditis, 291
asthma and, 443
bipolar spectrum disorders and, 179 Nail biting, 344
cardiac Naloxone, for opiate intoxication, 260
anxiety and, 333 Naltrexone, for alcoholism, 251
depression and, 330–331 Narcolepsy, 203
chronic obstructive pulmonary Narcotics. See Opiates
disease and, 441, 442 National Comorbidity Survey
cocaine-related, 265 Replication, 160
delirium and, 98 National Institute of Mental Health
delirium tremens and, 253 (NIMH), 3
dementia and, 120 Nausea/vomiting
depression and, 162, 330–331 anticipatory, 387
poststroke, 457 chemotherapy-induced, 432
diabetes mellitus and, 361 hyperemesis gravidarum, 152, 387,
eating disorders and, 148 417, 421–422
subdural hematoma and, 452 hypnosis and/or relaxation for, 313
suicide, 69–75 self-induced, 146, 149, 150, 151, 151
Movement disorders, sleep-related, 205 Nefazodone, 472
MRI. See Magnetic resonance imaging Neural tube defects, 421
MSE. See Mental status examination Neurasthenia, 374
MSLT (Multiple Sleep Latency Test), Neuroimaging
197 in anxiety disorders, 81
Multiple sclerosis, 82, 165, 181, 205, in dementia, 135, 137
386 Alzheimer’s disease, 135
Multiple Sleep Latency Test (MSLT), 197 HIV-associated, 403
Munchausen syndrome, 235. vascular dementia, 125
See also Factitious disorders in eating disorders, 149
Mutism, 32 of traumatic brain injury, 452–453
MWT (Maintenance of Wakefulness Neuroleptic malignant syndrome
Test), 197 (NMS), 90, 285–289
Mycophenolate mofetil, 472 antipsychotic use after, 289
Myocardial infarction (MI), 81, 102, clinical features of, 287
159, 210 differential diagnosis of, 286–287,
anxiety and, 332–333 288
depression and, 330 drugs associated with, 285
 Index 521

as idiopathic drug reaction, 285 Nonsteroidal anti-inflammatory drugs

incidence of, 285 (NSAIDs)
laboratory findings in, 288 in fibromyalgia, 381
risk factors for, 285 gastrointestinal bleeding induced by,
time course of, 285, 287 392
treatment of, 289 peptic ulcer disease induced by, 385,
Neurological disorders, 82 387
conversion disorder and, 228 Norepinephrine, in anxiety, 80
delirium due to, 102 Norfluoxetine, 170
dementia and, 120–121 Nortriptyline
dysphagia and, 386 during breast-feeding, 419
HIV disease and, 401 for depression, in STAR*D study,
mania due to, 181, 181–182 176
vs. neuroleptic malignant syndrome, Not otherwise specified (NOS)
288 diagnoses, 7
Neurological examination, 46–47 NREM (non–rapid eye movement)
Neuromuscular abnormalities sleep, 195–196
in malignant hyperthermia, 286 NSAIDs. See Nonsteroidal anti-
in neuroleptic malignant syndrome, inflammatory drugs
286, 287 Nutrition
in serotonin syndrome, 284, 286 deficiencies of, 367–368
Neuroplasticity, 234, 460 after bariatric surgery, 320, 367
Neuropsychiatric Inventory, 140 in eating disorders, 151–152
Neuropsychiatrist, 46–47 refeeding syndrome and, 153–154
Neuropsychological testing, 135, 136
Neurosyphilis, 82, 102 Obesity, 151, 179, 374
Neuroticism, 376 bariatric surgery for, 155, 319–327
Niacin deficiency, 101, 367 diabetes mellitus and, 152
Nicotine withdrawal, 442 metabolic syndrome and, 291
Night eating syndrome, 147 sleep-related breathing disorders
bariatric surgery and, 322, 324 and, 202, 203
Nightmare disorder, 204 Observation, 8, 31–32
NIMH (National Institute of Mental Obsessive-compulsive disorder (OCD),
Health), 3 83
NMS. See Neuroleptic malignant bariatric surgery and, 322
syndrome body dysmorphic disorder and, 231,
Non–rapid eye movement (NREM) 232
sleep, 195–196 eating disorders and, 148
parasomnias of, 204 postpartum, 412
522 Clinical Manual of Psychosomatic Medicine

Obsessive-compulsive disorder (OCD) for periodic limb movement

(continued) disorder, 205
treatment of, 92 tolerance to, 259–260
deep brain stimulation, 295–296 withdrawal from, 261
trichotillomania and, 343–344 Oral drug administration, 274
Obsessive-compulsive personality Orientation. See also Disorientation
disorder, 221 assessment of, 37
Obstetrics, 411–422. Orthostatic hypotension, 291
See also Pregnancy Osteopenia, 150
Obstructive sleep apnea, 196, 197, Osteoporosis, 366–367
202–203, 321 Outpatient consultation, 5, 10–11
OCD. See Obsessive-compulsive collaborative, 10
disorder integrated care, 10–11
Off-label drug use, 26 for management of suicidal patient,
Olanzapine 75
adverse effects of for patient education, 309, 311
cardiac effects, 290–291 with suicidal patients, 69
metabolic syndrome, 292 traditional, 10
pancreatitis, 294 Overdose of drug. See also Intoxication
for agitation and aggression in alcohol, 251–252
dementia, 140 benzodiazepines, 258
for anorexia nervosa, 154 intentional, 71
for bipolar depression, 185–186 opiates, 260–261
for delirium, 111, 112, 112 Oxazepam, 86, 88
for delusional parasitosis, 340 for alcohol withdrawal, 249
for trichotillomania, 344 for insomnia, 201
Olanzapine/fluoxetine, for depression, in liver disease, 294
174
in bipolar disorder, 185–186 PACT (Psychosocial Assessment of
Olfactory reference syndrome, 341 Candidates for Transplantation),
Oncology, 427–437. 471
See also Cancer Pain
Ondansetron, 429 in cancer, 433
Opiates, 101 chronic, 72
abuse/dependence on, 234, in fibromyalgia syndrome,
259–261 378–381
in fibromyalgia, 381 head trauma and, 454, 455
intoxication with, 260–261 pelvic, 388
for pain, 260, 433 in dementia, 137
 Index 523

depression and, 433 Paranoia, 33

hypnosis or relaxation for, 313 Paranoid personality disorder, 221
in irritable bowel syndrome, Paraphasias, 32
388–389 Paraplegia, 460, 461
opiates for, 260, 433 Parasitosis, delusional, 215, 339,
sleep disturbances and, 196 340–341
in somatization disorder, 221 clinical presentation of, 340
Pain disorder, 233–235 nonpharmacological approaches to,
clinical course and prognosis for, 341
234 pharmacological management of,
clinical features of, 233–234 340
cognitive therapy for, 220 Parasomnias, 204–205
differential diagnosis of, 234 Parathyroid disorders, 365–366
malingering, 238 Parenteral drug administration, 274
epidemiology of, 233 Parkinsonism
management of, 235 antipsychotic-induced, 141, 287
psychiatric comorbidity with, 234 in dementia with Lewy bodies, 127
suicidality and, 234 Parkinson’s disease, 32, 34, 112, 159,
Paliperidone, 367 285, 386
Palliative care, 446 dementia of, 127
Palpitations, 333 depression in, 127, 165
Pancreatic cancer, 165 selegiline for, 173
Pancreatic injury, drug-induced, 394 sleep disturbances in, 204, 205
Pancreatitis, 250, 294 Paroxetine
Panic disorder, 82–83, 214 for anxiety
agoraphobia without, 83 generalized anxiety disorder, 87
asthma and, 443 obsessive-compulsive disorder,
chronic obstructive pulmonary 92
disease and, 442 panic disorder, 91
globus hystericus and, 386 posttraumatic stress disorder,
irritable bowel syndrome and, 389 355
noncardiac chest pain in, 83, 333, social anxiety disorder, 92
387 for depression, 177
pain disorder and, 234 in bipolar disorder, 185
psychotherapy for, 92 in diabetes mellitus, 362
psychotropic drug therapy for, in HIV disease, 406
91–92 in pregnancy and breast-feeding,
pulmonary hypertension and, 446 415, 417, 419
somatization disorder and, 221 drug interactions with, 170, 429, 435
524 Clinical Manual of Psychosomatic Medicine

Paroxetine (continued) long-suffering, complaining

elimination half-life of, 170 patients, 57–58
in irritable bowel syndrome, 389 orderly, controlling patients, 56
in liver disease, 293 seclusive, aloof patients, 60–61
in renal disease, 292 superior, critical patients, 59–60
Paroxysmal atrial tachycardia, 81 timid, apprehensive patients,
Passive aggression, 66 63–64
Patient Health Questionnaire–9 postconsultation care of, 9, 307–
(PHQ-9), 169, 414 308
Patient Self-Determination Act, 19 practical concerns of, 306–308
Patients promoting resilience of, 308,
culture of, 301–302 310–311
defense mechanisms of, 64–65 safety of, 306–307
educational interventions for seclusion and restraint of, 14, 25–26
(See Psychoeducation) spiritual, existential, and religious
ethnicity of, 302–303 beliefs of, 305–306
factors affecting response to medical substitute decision makers for, 14,
illness and hospitalization, 23–24
51–54 suicidal, 69–75
meaning of illness, 54 Pediatric patients
nature of the disease, 52–53 factitious disorder by proxy in, 236
personality and past history, HIV disease in, 400
53–54 Pellagra, 367
financial worries of, 306 Peptic ulcer disease, 385, 387
language barriers of, 303 Perceptual disturbances, 33–34
use of interpreters for, 304–305 during alcohol withdrawal, 249
optimizing constructive coping by, in Alzheimer’s disease, 123
65–66 in delirium, 106
personality patterns of, 54–64 in disaster and terrorism casualties,
cold, deceitful patients, 62–63 353
dependent, demanding patients, Peregrination, 235
55 Perfectionism, 148
dramatizing, emotional patients, Pericardial effusions, 150
56–57 Periodic limb movement disorder
guarded, suspicious patients, (PLMD), 205
58–59 Personality, 51–65
idealizing, provocative patients, 62 chronic fatigue syndrome and, 376
impulsive, acting-out patients, defense mechanisms and, 64–65
61–62 eating disorders and, 148
 Index 525

helping patient cope constructively, Pharmacokinetics

65–66 after bariatric surgery, 320, 324,
hypochondriasis and, 225 325–327
impact on response to medical in medically ill patients, 274–277
illness/hospitalization, 53–54 drug absorption, 274
patterns of, 54–64 drug distribution, 274, 276
cold, deceitful patients, 62–63 drug elimination, 277
dependent, demanding patients, drug metabolism, 276–277
55 Phenelzine, 173
dramatizing, emotional patients, Phenobarbital, 101
56–57 for alcohol withdrawal, 249
guarded, suspicious patients, seizures, 252
58–59 Phenylephrine, 82, 101
idealizing, provocative patients, Phenytoin, 101, 198
62 Pheochromocytoma, 80, 82, 367
impulsive, acting-out patients, Phobias, 83
61–62 agoraphobia, 83, 431
long-suffering, complaining in cancer, 431
patients, 57–58 PHQ-9 (Patient Health Questionnaire–
orderly, controlling patients, 56 9), 169, 414
seclusive, aloof patients, 60–61 Physical therapy, in conversion disorder,
superior, critical patients, 219, 230
59–60 Pick’s disease, 129
timid, apprehensive patients, Pimozide, 290
63–64 for delusional parasitosis, 340
Personality changes Platelet activity in cardiovascular disease
in frontotemporal dementia, 129 and depression, 331
head trauma and, 454 PLMD (periodic limb movement
Personality disorders, 51, 53–54. disorder), 205
See also specific personality disorders PM. See Psychosomatic medicine services
HIV disease and, 405 Pneumonia, 82
treatment of, 408 Pneumothorax, 82
somatization and, 215, 221 Polysomnography, 197, 203
suicide and, 71 Portal hypertension, 321
“Phantom limb” sensation, 34 Postconsultation care, 307–308
Pharmacodynamic drug interactions, Postencephalitic syndromes, 82
277 Postoperative patients, 102
Pharmacokinetic drug interactions, Postpartum Depression Screening Scale,
277 414
526 Clinical Manual of Psychosomatic Medicine

Postpartum women. See also Pregnancy bipolar disorder treatment in,

anxiety disorders in, 412 420–421
bipolar disorder in, 420–421 depression in, 412, 413–418
high recurrence risk for, 420 medical comorbidity with, 414
mood stabilizers for, 420–421 preterm delivery and, 413
blues in, 412 screening for, 414
depression in, 153, 412 treatment of, 414–418
treatment of, 419 eating disorders and, 152–153
eating disorders in, 152–153 epidemiology of psychiatric
psychosis in, 413 disorders associated with,
Posttraumatic stress disorder (PTSD), 84 411–412
asthma and, 443 anxiety disorders, 412
bariatric surgery and, 322 mood disorders, 412
cancer and, 431 postpartum psychosis, 413
chronic obstructive pulmonary schizophrenia, 413
disease and, 442 substance abuse, 412
in disaster and terrorism casualties, hyperemesis gravidarum in, 152, 387
354–355 treatment of, 417, 421–422
head trauma and, 454, 455 Prescribing drugs for nonapproved uses,
HIV disease and, 404–405, 408 26
nightmares in, 204 Preterm birth, 413, 415
pain disorder and, 234 Primary care outpatient settings, 10
in pregnancy, 412 Privacy. See also Confidentiality
spinal cord injury and, 461 for cognitive examination, 36
treatment of, 93, 354–355, 355 vs. consultee need to know, 15
for insomnia, 201–202 HIPAA standards for, 9, 15–16
Pramipexole, for periodic limb Procainamide, 101
movement disorder, 205 Procaine, 82
Prazepam, 88 Procarbazine, 82, 436
Prazosin, for posttraumatic stress Progressive multifocal
disorder, 354 leukoencephalopathy, 402
Prednisone, for inflammatory bowel Projection, 66
disease, 391 Promethazine, 285
Preeclampsia, 415–417 Propofol, for delirium, 115, 444
Pregabalin Propranolol, for panic disorder, 92
for anxiety in chronic obstructive Prosody, 32
pulmonary disease, 442 ProSom. See Estazolam
for fibromyalgia, 380–381 Prostacyclins, for pulmonary
Pregnancy, 205, 411–422 hypertension, 446
 Index 527

Protein binding of drug, 276 outpatient groups for, 309, 311

Proton-pump inhibitors, 387 for psychotropic drug therapy, 274,
Proverb interpretation, 38 307
Pruritus, idiopathic, 339, 342 Psychosis
Pseudobulbar affect, 454, 458, 460 alcohol-induced, 252
Pseudoephedrine, 82 in Alzheimer’s disease, 123
Pseudologia fantastica, 235 amphetamine-induced, 264
Psoriasis, 345 vs. anxiety, 85
Psychiatric disorders cocaine-induced, 267
anxiety disorders, 79–93 in HIV disease, 401
bariatric surgery and, 321–327 monosymptomatic hypochondriacal,
bipolar disorder, 178–186 215
delirium, 97–116 postpartum, 413
dementia, 119–141 in sarcoidosis, 446
depression, 159–178 schizophrenia in pregnancy, 413
in disaster and terrorism casualties, somatic symptoms of, 214–215
349–357 suicide and, 74
eating disorders, 145–155 Psychosocial Assessment of Candidates
frequency among hospital for Transplantation (PACT),
inpatients, 5 471
impact on health care costs, 6 Psychosocial management, 301–313.
not otherwise specified, 7 See also Psychotherapy
sleep disorders, 195–205 culture and, 301–302
somatoform disorders, 209–239 ethnicity and, 302–303
substance-related disorders, language and, 303–305
245–267 patient’s practical concerns and,
suicidality, 69–75 306–308
Psychocutaneous disorders. financial worries, 306
See Dermatological disorders postconsultation care,
Psychodynamic psychotherapy, 312 307–308
for depression, 178 safety, 306–307
in cancer, 430 to promote resilience rather than
for generalized anxiety disorder, vulnerability, 308, 310–311
90 spiritual, existential, and religious
Psychoeducation factors and, 305–306
about community resources, 308 supportive tools for, 308–313
for anxiety in cancer, 431 education, 309, 311
for depression in cancer, 430 hypnosis and relaxation, 313
at hospital bedside, 309 psychotherapy, 311–313
528 Clinical Manual of Psychosomatic Medicine

Psychosomatic medicine (PM) services. posttraumatic stress disorder,

See also Consultation-liaison 93, 355
psychiatrist atopic dermatitis, 346
business of, 5–6 body dysmorphic disorder, 233
cost-effectiveness of, 6 chronic fatigue syndrome,
history of, 3–4 376–377
integrated care and, 4, 5 conversion disorder, 229
maintaining financial viability of, 6 delusional parasitosis, 341
medicolegal issues in, 13–27 demoralization, 165
in outpatient settings, 5, 10–11 depression, 178
reimbursement for, 4, 7, 11 in cancer, 430
subspecialty certification for, 4, 5 in diabetes mellitus,
trends affecting practice of, 4–5 362–363
Psychostimulants, 173–174 postpartum, 419
adverse effects of, 174, 430 poststroke, 459
for depression, 173 in pregnancy, 415
in cancer, 430 eating disorders, 154–155
in HIV disease, 407 fibromyalgia, 381
poststroke, 459 HIV/AIDS, 405
in ventilator-dependent patients, hypochondriasis, 226
445 idiopathic pruritus, 342
indications for, 173, 174 inflammatory bowel disease,
in traumatic brain injury, 456 391–392
Psychotherapy, 311–313. irritable bowel syndrome, 389
See also specific psychotherapies psoriasis, 345
for bariatric surgery, 325, 326 somatoform disorders, 220
in primary care settings, 10 spinal cord injury, 462
in specific disorders suicidality, 74
anxiety trichotillomania, 344
acute anxiety and generalized Psychotropic drug therapy, 273–294.
anxiety disorder, 90–91 See also Medications; specific drugs
acute stress disorder, 93 and classes
in asthma, 443 adherence to, 273–274
in cancer, 431–432 doctor–patient relationship and,
in chronic obstructive 273, 406
pulmonary disease, education for, 274
442 adverse effects of, 282–292
health anxiety, 93 cardiac effects, 289–291
panic disorder, 92 metabolic syndrome, 291–292
 Index 529

neuroleptic malignant syndrome, anxiety

90, 285–289, 286–287 acute anxiety and generalized
serotonin syndrome, 87, 282, anxiety disorder, 86–90,
282–285, 283, 286–287 88–89
thyroid dysfunction, 292 in asthma, 443
antidepressants, 169–173 in cancer, 432
anxiolytics, 86–90, 88–89 in chronic obstructive
bariatric surgery and, 320, 324, pulmonary disease,
325–327 442
drug interactions with, 277, obsessive-compulsive
278–281 disorder, 92
ethnicity and, 303 panic disorder, 91–92
in heart disease, 335, 469 posttraumatic stress disorder,
in liver disease, 293–294, 469 354–355, 355
in lung disease, 469 social anxiety disorder, 92
mood stabilizers, 182–185 benzodiazepine overdose, 258
patient education for, 274, 307 binge-eating disorder and
pharmacokinetics in medically ill obesity, 155
patients, 274–277 body dysmorphic disorder, 233,
during pregnancy and breast- 342
feeding, 416 bulimia nervosa, 155
antidepressants, 415–418 cancer-related fatigue, 434
antipsychotics, 421–422 conversion disorder, 230
benzodiazepines, 420 delirium, 26, 111–116, 112,
mood stabilizers, 420–421 113
prescribing drugs for nonapproved delusional parasitosis, 340
uses, 26 depression, 169–177
principles for, 275 in bipolar disorder, 185–186
psychostimulants, 173–174, 174 in cancer, 429–430
in renal disease, 292–293, 468–469 in cardiovascular disease,
in specific disorders 334–335
agitation and aggression in in diabetes mellitus,
dementia, 139–141 362–363
alcoholism, 250–251 in disaster and terrorism
intoxication, 248 casualties, 354
withdrawal, 249–250 postpartum, 419
amphetamine intoxication, 263, in pregnancy, 415–418
264 in STAR*D study, 175–177
anorexia nervosa, 154 in thyroid disease, 364
530 Clinical Manual of Psychosomatic Medicine

Psychotropic drug therapy, in specific Pulmonary embolus, 82, 98

disorders (continued) Pulmonary medications, psychiatric
fibromyalgia, 380–381 effects of, 447–448
HIV/AIDS, 405–408 Pulmonary rehabilitation, 442, 443, 445
hypochondriasis, 225 Purpura, psychogenic, 343
idiopathic pruritus, 342 Pyridoxine deficiency, 368
inflammatory bowel disease,
391–392
insomnia, 198, 200–202, 201 QIDS-SR (Quick Inventory of
irritable bowel syndrome, 389 Depressive Symptomatology
mania, 182–185 Self-Report), 175
neuroleptic malignant QTc interval prolongation
syndrome, 289 drug-induced, 289–291
onychophagia, 344 antipsychotics, 112, 113, 114,
opiate dependence, 260–261 115, 141, 290–291
pain disorder, 235 selective serotonin reuptake
periodic limb movement inhibitors, 290
disorder, 205 tricyclic antidepressants, 172, 289
pseudobulbar affect, 460 eating disorders and, 150
sedative-hypnotic withdrawal, 259 factors associated with, 291
serotonin syndrome, 284–285 Quadriplegia, 460, 461
spinal cord injury, 462 Quality of life after transplant surgery,
stroke, 459–460 473
traumatic brain injury, 456 Quazepam, 88
trichotillomania, 344 Quetiapine
PTSD. See Posttraumatic stress disorder for agitation and aggression in
Pulmonary conditions, 72, 79, 82, 102, dementia, 140
162, 196, 374, 441–448 for anorexia nervosa, 154
asthma, 443–444 for bipolar depression, 185
chronic obstructive pulmonary for delirium, 111, 112, 112
disease, 441–443 for delusional parasitosis, 340
hyperventilation syndrome, 447 for insomnia, 201–202
psychotropic drug therapy in, 469 metabolic syndrome induced by,
pulmonary hypertension, 446–447 292
restrictive lung diseases, 445–446 for posttraumatic stress disorder, 355
idiopathic pulmonary fibrosis, 445 Quick Inventory of Depressive
sarcoidosis, 446 Symptomatology Self-Report
tuberculosis, 447 (QIDS-SR), 175
ventilator dependence, 444–445 Quinacrine, 101
 Index 531

Quinidine, 101 for psoriasis, 345

for somatoform disorders, 220
Ramelteon, for insomnia, 200, 201 Religious beliefs, 305–306
Ranitidine, 101 REM (rapid eye movement) sleep, 102,
Rapid eye movement (REM) sleep, 195–196
195–196, 203 parasomnias of, 204
parasomnias of, 204 REM sleep behavior disorder, 127, 204
Rationalization, 66 Renal disease/failure, 72, 101, 196,
Rectal drug administration, 274 205, 374
Refeeding syndrome, 154, 254 drug absorption in, 274
Referring physician psychotropic drug use in, 292–293,
balancing patient privacy against 468–469
consultee need to know, 15 acamprosate, 251
as “customer,” 7, 8 antidepressants, 292
outpatient consultation with, 10–11 antipsychotics, 293
Refusal of treatment, 14 benzodiazepines, 293
advance directives and, 19–20 mood stabilizers, 293
capacity evaluation for, 21–22, Renal drug excretion, 277, 468–469
73–74 Repression, 66
do-not-resuscitate and do-not- Resilience, promotion of, 308,
intubate orders, 18–19 310–311
by Jehovah’s Witness, 16 Respiratory alkalosis, 447
Regression, 51, 55 Respiratory depression, drug-induced
Rehabilitation medicine, 451–462 opiates, 257, 260
in spinal cord injury, 460–462 sedative-hypnotics, 257, 258
in stroke, 457–460 Restless legs syndrome (RLS), 82, 196,
in traumatic brain injury, 451–456 197, 205
Reimbursement, 4, 7, 11 Restoril. See Temazepam
Relaxation techniques, 91, 313 Restraint of patient, 14, 25–26
for acne, 345 Rhabdomyolysis, 288
for anxiety Rifampin, 101, 448
in asthma, 443 Right to direct medical treatment, 17–20.
in cancer, 431 See also Refusal of treatment
in chronic obstructive pulmonary advance directives, 19
disease, 442 do-not-resuscitate and do-not-
panic disorder, 92 intubate orders, 18–19
for atopic dermatitis, 346 power of attorney, 19–20
for fibromyalgia, 381 signing out against medical advice,
for insomnia, 198 17–18
532 Clinical Manual of Psychosomatic Medicine

Risperidone Sedative-hypnotics.
adverse effects of See also Benzodiazepines
hyperprolactinemia, 367 abuse of, 100, 257–259
metabolic syndrome, 292 “shopping bag sign” of, 257
pancreatitis, 294 cognitive effects of, 101, 259
for agitation and aggression in cross-reactivity between, 258
dementia, 140, 141 for insomnia, 200, 201
for anorexia nervosa, 154 intoxication with, 258
for delirium, 111, 112, 112 nonbenzodiazepine, 200, 201
for delusional parasitosis, 340 withdrawal from, 82, 258–259
with lithium for mania, 183 Seizures, 82, 102. See also Epilepsy
for trichotillomania, 344 alcohol withdrawal, 252–253
Rivastigmine, for dementia, 138 after head trauma, 452
RLS (restless legs syndrome), 82, 196, in HIV disease, 401
197, 205 psychogenic nonepileptic, 227,
Ropinirole, for periodic limb 228–229
movement disorder, 205 vagal nerve stimulation for, 295
Roux-en-Y gastric bypass, 320. Selective serotonin reuptake inhibitors
See also Bariatric surgery (SSRIs), 169–170.
See also specific drugs
SADHART (Sertraline Antidepressant active metabolites and elimination
Heart Attack Randomized Trial), half-life of, 170
334–335 adverse effects of, 169–170, 198, 429
Safety concerns, 306–307 cardiac effects, 290
domestic abuse or violence, 307 gastrointestinal effects, 386, 392
incapacity and, 307 in neonates, 415, 417
involuntary hospitalization for, 24– osteoporosis, 366
25 preterm birth, 413, 415
protection of suicidal patient, 73 for anorexia nervosa, 154
seclusion and restraint for, 25–26 for anxiety
Salicylates, 82 in cancer, 432
Sarcoidosis, 446 in chronic obstructive
Schizophrenia pulmonary disease, 442
in pregnancy, 413 generalized anxiety disorder, 87
suicide and, 71 obsessive-compulsive disorder, 92
SCI. See Spinal cord injury panic disorder, 91
Scopolamine, 101 posttraumatic stress disorder,
Seclusion and restraint of patient, 14, 354, 355
25–26 social anxiety disorder, 92
 Index 533

benefits of, 169 Sepsis, 102

for body dysmorphic disorder, 233, Sequenced Treatment Alternatives to
342 Relieve Depression (STAR*D)
for bulimia nervosa, 155 study, 175–177
for delusional psychocutaneous design of, 175
disorders, 341 first-step treatment: citalopram,
for depression, 169–170, 177 175–176
in cancer, 429 fourth-step treatment, 176
in cardiovascular disease, goal of, 175
334–335 implications for clinical practice,
in diabetes mellitus, 362 176–177
in HIV disease, 406 remission rates and dosages in, 175
interferon-induced, 429 second-step treatment, 176
poststroke, 459, 460 third-step treatment, 176
in STAR*D study, 175–176 Serax. See Oxazepam
discontinuation syndrome with, Serial 7s or 3s, 37
170 Serotonin, in anxiety, 80
drug interactions with, 170, 406, Serotonin-norepinephrine reuptake
429 inhibitors (SNRIs), 170–171.
for fibromyalgia, 380 See also specific drugs
for hot flashes in cancer patients, adverse effects of, 170, 392
169, 170, 435 for depression, 170–171, 177
for hypochondriasis, 225 in cancer, 430
for inflammatory bowel disease, 392 in diabetes mellitus, 362
with interferon-α in hepatitis B for diabetic neuropathy, 170
virus infection, 393 for fibromyalgia, 170, 171, 380
for irritable bowel syndrome, 389 for generalized anxiety disorder, 87
in liver disease, 293 for hot flashes in cancer patients,
during pregnancy and breast- 170, 435
feeding, 413, 415–417, 419 for inflammatory bowel disease, 392
in pregnancy and breast-feeding, for pain disorder, 235
415–417 in pregnancy, 417
for pseudobulbar affect, 460 for social anxiety disorder, 92
in renal disease, 292 Serotonin syndrome, 87, 282–285
in spinal cord injury, 462 clinical findings in, 283, 283–284
in traumatic brain injury, 456 diagnosis of, 284
for trichotillomania, 344 differential diagnosis of, 284,
Selegiline, 173 286–287, 288
Self-determination, 14, 19 drug rechallenge after, 285
534 Clinical Manual of Psychosomatic Medicine

Serotonin syndrome (continued) hepatitis C virus infection and, 393

drugs associated with, 282 somatoform disorders and, 215,
management of, 284–285 217–218
as non-idiopathic drug reaction, Signing out against medical advice
282 (AMA), 17–18
Sertraline, 170 documentation of, 17–18
for anxiety patient capacity and, 17
generalized anxiety disorder, 87 Sildenafil, for pulmonary hypertension,
obsessive-compulsive disorder, 446
92 Skin disorders.
panic disorder, 91 See Dermatological disorders
posttraumatic stress disorder, Skull fracture, 453
355 Sleep apnea
social anxiety disorder, 92 central, 202
for depression, 177 obstructive, 196, 197, 202–203,
in cardiovascular disease, 321
334–335 Sleep disorders, 195–205, 374
in HIV disease, 406 circadian rhythm sleep disorders,
interferon-induced, 429 203–204
in pregnancy and breast-feeding, depression and, 163, 195
417, 419 evaluation of, 196–197
in STAR*D study, 176 hypersomnias of central origin, 203
drug interactions with, 472 insomnia, 197–202
in liver disease, 293 medical illness and, 196
in renal disease, 292 parasomnias, 204–205
Sertraline Antidepressant Heart Attack sleep-related breathing disorders,
Randomized Trial (SADHART), 202–203
334–335 sleep-related movement disorders,
Set Test, 42, 44 205
Sexual dysfunction, spinal cord injury Sleep hygiene, 198, 199
and, 461 Sleep paralysis, 203
Shift work sleep disorder, 203 Sleep restriction therapy, 198
Shock, 102 Sleep stages, 195–196
Short Test of Mental Status (STMS), Sleep terrors, 204
40, 134, 136 Sleepwalking, 204, 205
Sibutramine, for binge-eating disorder, Smoking
155 Alzheimer’s disease and, 122
Sickness behavior bipolar disorder and, 179
depression and, 360 cessation of, 442, 443
 Index 535

depression and, 160, 161 delusional disorders, 215

after heart transplantation, 473 medical disorders, 214
obstructive sleep apnea and, 203 mood disorders, 214
Snoring, 203 personality disorders, 215
SNRIs. See Serotonin-norepinephrine psychotic disorders, 214–215
reuptake inhibitors substance-related disorders, 214
Social anxiety disorder, 83 conversion disorder, 226–230
bariatric surgery and, 322 distinguishing between disease and
body dysmorphic disorder and, 231, illness, 210
232 evaluation of, 215–218
eating disorders and, 148 hypochondriasis, 224–226
treatment of, 92 illness behavior in, 215, 217–218
Solubility of drugs, after bariatric inadequacy of conventional
surgery, 326 treatment for, 212–213
Soma. See Carisoprodol management of, 218–220
Somatization, fibromyalgia and, 379 cognitive therapy, 220
Somatization disorder, 221–222 consequences of failure to
clinical course and prognosis for, engage the patient, 220
222 group psychotherapy, 220
clinical features of, 221 guidelines for, 218–219
diagnostic criteria for, 221 physical reactivation and
differential diagnosis of, 221–222 physical therapy, 219
malingering, 238 relaxation therapies,
epidemiology of, 221 biofeedback, meditation,
management of, 222 and hypnotherapy, 220
psychiatric comorbidity with, 221 neurological examination in, 46–47
hypochondriasis, 225 nosology for, 213
Somatoform disorder(s), 209–239 pain disorder, 233–235
approach to, 215–220 presentations of, 212
bariatric surgery and, 322 somatization disorder, 221–222
body dysmorphic disorder, 230–233 undifferentiated, 222–224
challenging arena of, 210–211 clinical course and prognosis for,
clues to, 211 223
common feature of, 212, 215 clinical features of, 223
comorbidities and differential differential diagnosis of, 223
diagnosis of, 213–215 epidemiology of, 222–223
adjustment disorders, 214 management of, 223–224
anxiety disorders, 214 viscosity between societal mores and
cognitive disorders, 214 somatic symptoms, 213
536 Clinical Manual of Psychosomatic Medicine

Sorafenib, 437 defenses to cope with, 64–65

Specialty care outpatient settings, 10–11 helping patient cope constructively
Specific phobias, 83 with, 65–66
somatization disorder and, 221 patient factors affecting response to,
treatment of, 92 51–54
Speech meaning of illness, 54
assessment of, 32 nature of the disease, 52–53
impairments of, in delirium, 106 personality and past history, 53–54
Spinal cord injury (SCI), 460–462 personality patterns and, 54–64
alcohol abuse/dependence and, 461 Stress-related disorders
depression and, 461 acne, 345
epidemiology of, 460 acute stress disorder, 83–84, 93, 354
posttraumatic stress disorder and, atopic dermatitis, 345–346
461 chronic fatigue syndrome, 376
psychological assistance in, 462 conversion disorder, 226, 228
psychotropic drug therapy in, 462 in disaster and terrorism casualties,
sexual dysfunction and, 461 349–357
Spirituality, 305–306 irritable bowel syndrome, 388–389
Splitting, 66 peptic ulcer disease, 387
SSRIs. See Selective serotonin reuptake posttraumatic stress disorder, 84,
inhibitors 93, 354–355
Standard of care, 27 psoriasis, 345
Stanford Sleepiness Scale, 197 Stroke, 32, 82, 102, 159, 386, 457–460
STAR*D. See Sequenced Treatment antipsychotic-related, 141
Alternatives to Relieve Depression epidemiology of, 457
study neuropsychiatric effects of, 457–460
Status epilepticus, 102 anxiety, 457
Statutory commitment, 24 behavioral changes, 458
Steady-state drug level, 276 catastrophic reaction, 458
STEP-BD (Systematic Treatment cognitive impairment, 457
Enhancement Program for Bipolar delirium, 457
Disorder), 185 depression, 161, 457
Stimulus control therapy, for insomnia, fatigue, 459
198 mania, 181, 182
STMS (Short Test of Mental Status), pseudobulbar affect, 458
40, 134, 136 treatment of, 459–460
Stress of medical illness/hospitalization, Subdural hematoma, 102, 452
51–52 Sublingual drug administration, 274
anxiety due to, 79 Subspecialty certification, 4, 5
 Index 537

Substance-induced disorders substance abuse, 246

alcohol-induced psychotic disorder, substance dependence, 246–247
252 tuberculosis and, 447
amphetamine-induced psychotic Substitute decision maker, 14, 23–24
disorder, 264 guardianship, 23–24
anxiety, 81, 82, 86 legal establishment of, 23
cocaine-induced psychotic disorder, Suicide, 69–75
267 assessing risk for, 35, 71–72
delirium, 100, 101 attempted, 70–71
mania, 181, 182 history of, 71–72
sedative-, hypnotic-, or anxiolytic- completed, 69–70
induced persisting amnestic epidemiology of, 69–71
disorder, 259 institutional response to, 70
Substance-related disorders, 245–267 lithium for prevention of, 182–183
alcohol, 247–257 medical illness and, 70, 71, 72, 163
amphetamines, 261–264 cancer, 428
attitudes of medical staff about methods of, 69, 70
persons with, 245 drug overdose, 71
bariatric surgery and, 322, 325 psychiatric disorders and, 70, 71,
cocaine, 264–267 74
in disaster and terrorism casualties, alcoholism, 254
357 body dysmorphic disorder, 232
DSM-IV-TR criteria for, 246 depression, 70, 71, 74
head trauma and, 454–455 pain disorder, 234
hepatitis C virus infection and, psychological factors and, 72
392–393 treatment and management of,
HIV disease and, 404, 407–408 72–75
opiates, 259–261 document communications, 74
in pregnancy, 412 in emergency department or
psychiatric comorbidity with outpatient setting, 75
anxiety disorders, 85 establish capacity when patients
body dysmorphic disorder, 231 reject life-prolonging
delirium, 100 treatments, 73–74
depression, 159 identifying risk level, 72–73
eating disorders, 148 psychiatric hospitalization, 73
somatization disorder, 214, 221 psychiatric treatment, 74
suicidality, 70, 71, 74 psychotherapy, 74
sedative-hypnotics and anxiolytics, remove risk factors, 74–75
257–259 secure surroundings, 73
538 Clinical Manual of Psychosomatic Medicine

Sunitinib, 437 Temazepam, 88

Supportive psychotherapy, 312 for insomnia, 201
for anxiety in liver disease, 294
in cancer, 431 Temporal lobes, 81
generalized anxiety disorder, 90 Temporomandibular joint disorder,
panic disorder, 92 388
for conversion disorder, 229 Terminally ill patients
for depression, 178 advance directives for, 13–14,
in cancer, 430 19–20
Suppression, 65 end-of-life care
Surgery in cancer, 435–437
bariatric, 155, 319–327 in pulmonary hypertension,
cardiac, 331 446–447
cosmetic, 232, 233 psychostimulants for depression in,
transplantation, 467–474 407
Suspiciousness, 33, 53, 58–59 suicide among, 72
Sympathomimetic agents, 82, 101 Terrorism. See Disaster and terrorism
Syncope, 81 casualties
Syndrome of inappropriate antidiuretic TERS (Transplant Evaluation Rating
hormone secretion, 170 Scale), 471
Syrup of ipecac, 150 Testosterone, 151
Systematic exposure and desensitization, Thalidomide, 436
91 Theophylline, 82, 101, 198, 448
Systematic Treatment Enhancement Therapeutic alliance.
Program for Bipolar Disorder See also Doctor–patient relationship
(STEP-BD), 185 adherence to psychotropic drug
therapy and, 273
with suicidal patient, 74
T3 (triiodothyronine), 151
Therapeutic privilege, 16–17
for antidepressant augmentation, Thiamine deficiency, 101, 152, 154,
174, 176, 364 253, 367
T4 (thyroxine), 151, 363–364 supplementation for, 248, 253–254
Tacrine, for dementia, 138 Thioridazine, 290–291
Tacrolimus, 472 Thought blocking, 33
Tamoxifen, 101, 429, 435, 436 Thought content, 37
Tangentiality, 33 assessment of, 33–34
Taxanes, 436 Thought processes
TBI. See Traumatic brain injury assessment of, 33
TCAs. See Antidepressants, tricyclic disorganized, in delirium, 106
 Index 539

Thyroid disease, 363–365. posttransplantation issues, 473–474

See also Hyperthyroidism; effect of psychiatric disorders on
Hypothyroidism survival, 473
cognitive dysfunction and, 363 immunosuppressive drug–
delirium due to, 364–365 related neuropsychiatric
depression and, 363–364 syndromes, 473–474
Thyroid function testing, 135 quality of life, 473
Thyroid-stimulating hormone, 150 resuming risky health behaviors,
Thyroxine (T4), 33–364, 151 473
TMS (transcranial magnetic pretransplantation issues, 468–471
stimulation), 295 end-organ failure, 468–469
Tocainide, 101 psychiatric evaluation,
Tocopherol deficiency, 368 469–471
Topical drug administration, 274 of donors, 469–470
Topiramate of recipients, 470–471
for binge-eating disorder, 155 psychiatric factors affecting medical
in bipolar disorder, 185 outcomes of, 468
in renal disease, 469 psychiatric symptoms in candidates
Torsade de pointes, antipsychotic- for, 467–468
induced, 115 rating scales of readiness for, 471
Tourette’s disorder, 83, 295–296 Tranxene. See Clorazepate
Toxoplasmosis, 401, 402 Tranylcypromine, 173, 176
Trail Making Test, 40, 44 Trauma
Tramadol, for fibromyalgia, 381 advanced trauma life support,
Transcranial magnetic stimulation 350–351
(TMS), 295 alcohol-related, 250
Transplant Evaluation Rating Scale disaster and terrorism casualties,
(TERS), 471 349–357
Transplantation, 467–474 spinal cord injury, 460–462
contraindications to, 470–471 Traumatic brain injury (TBI), 99, 102,
patient categories for, 468 120, 451–456
perioperative and postsurgical anxiety disorders and, 454
recovery period issues, 471–473 chronic pain after, 454
delirium and other secondary cognitive dysfunction due to, 454
psychiatric disorders, 471 epidemiology of, 451–452
drug interactions, 472–473 management of, 455–456
neuropsychiatric effects of mania and, 181, 182
immunosuppressive mood disorders and, 454
medications, 472 personality changes and, 454
540 Clinical Manual of Psychosomatic Medicine

Traumatic brain injury (TBI) Urinary tract infection, 99

(continued) Urine acidification, 262
primary, 452–453 Utilization of health care resources
cerebral contusion, 452 in anxiety disorders, 79–80
diffuse axonal injury, 453 cosmetic surgery and body
epidural hematoma, 453 dysmorphic disorder, 232, 233
subdural hematoma, 452 in delusional parasitosis, 340
prognostic factors for, 453 in depression, 160
secondary, 453 in hypochondriasis, 225
substance-related disorders and, in pain disorder, 234
454–455 by somatizing patients, 209, 219,
war-related, 455 220, 223
Trazodone
adverse effects of, 171, 291 Vagal nerve stimulation (VNS), 295
in Alzheimer’s disease, 141 Validation therapy, for dementia, 138
for depression, 171 Valium. See Diazepam
for insomnia, 201 Valproate
for panic disorder, 91 adverse effects of, 101, 184, 294,
Triazolam, 88, 201 421
Trichotillomania, 339, 343–344 for bipolar disorder, 184
Tricyclic antidepressants (TCAs). in HIV disease, 407
See Antidepressants, tricyclic for corticosteroid-induced mania,
Trifluoperazine, for delusional 432
parasitosis, 340 drug interactions with, 184, 185
Trihexyphenidyl, 101 in liver disease, 294
Triiodothyronine (T3), 151 during pregnancy and breast-
for antidepressant augmentation, feeding, 421
174, 176, 364 in renal disease, 293
Trimipramine, for atopic dermatitis, Valvular heart disease, 81
346 Vascular dementia, 123, 125
Tuberculosis, 447 Alzheimer’s disease and, 123
TWEAK questionnaire, 256 clinical features of, 125
Twin studies diagnostic criteria for, 126
of chronic fatigue syndrome, 376 pathophysiology of, 123
of eating disorders, 148 prevalence of, 123
prognosis for, 125
Ulcerative colitis, 389–392 Vasculitis, 102
Urinary incontinence, 72 Venlafaxine, 170
 Index 541

adverse effects of, 170 vitamin B6, 368

mania, 185 vitamin B9, 368
for anxiety vitamin B12, 101, 135, 368
generalized anxiety disorder, 87
vitamin D, 368
panic disorder, 91
Vitamin E, in dementia, 138, 368
social anxiety disorder, 92
VNS (vagal nerve stimulation), 295
for cataplexy, 203
for depression, 170, 177
Waiver of informed consent, 17
in cancer, 430
War-related injuries
in diabetes mellitus, 362
spinal cord injury, 461
poststroke, 459
traumatic brain injury, 455
in STAR*D study, 176
Water loading, 151
drug interactions with, 472
Weight gain. See also Obesity
in fibromyalgia, 380
in depression, 163
for hot flashes in cancer patients,
drug-induced
170
antipsychotics, 292
in pregnancy, 417
mirtazapine, 362, 392
in renal disease, 292, 469
tricyclic antidepressants, 362
Ventilator dependence, 82, 444–445
after spinal cord injury, 462
anxiety and, 444–445
Weight loss
delirium and, 444
in anorexia nervosa, 146
depression and, 445
after bariatric surgery, 319
Versed. See Midazolam
presurgical psychiatric disorders
Vertigo, 79
and, 322
Vigilance test, 43
presurgical psychiatric
Vinblastine, 101, 436
management and, 325
Vincristine, 101, 436
psychological issues affecting,
Vinorelbine, 436
323
Violence, domestic, 307
due to hyperemesis gravidarum, 387
Vision impairment, 99, 135
Wernicke-Korsakoff syndrome, 152,
Visuospatial impairment, in delirium,
250, 253–254, 367
106
Wernicke’s aphasia, 458
Vitamin C, for urine acidification, 262
Withdrawal from substance
Vitamin D, for osteopenia, 150
alcohol, 248–250
Vitamin deficiencies, 367–368
amphetamines, 263
vitamin B1, 101, 152, 154, 253,
anxiety due to, 82
367 benzodiazepines, 87, 258–259
vitamin B3, 367 neonatal, 418
542 Clinical Manual of Psychosomatic Medicine

Withdrawal from substance (continued) Xanax. See Alprazolam

cocaine, 266–267
delirium due to, 101 Yohimbine, 82
in disaster and terrorism casualties,
357 Zaleplon, 201
vs. neuroleptic malignant syndrome, Ziprasidone
289 cardiac effects of, 290
nicotine, 442 for delirium, 112, 112
opiates, 261 mortality risk with, 114
sedative-hypnotics, 82, 258–259 Zolpidem, 201, 204–205
Worthlessness, 308 Zopiclone, 200