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![Treatment resistant Schizophrenia
• About up to 30% will experience persistent symptoms
• Referred to as treatment resistant schizophrenia
• or treatment refractory or incomplete recovery
Criteria
• Persistent positive symptoms and poor response to medication
• No period of good functioning in preceding 5 years
• Failure to respond after three periods of treatment with antipsychotics
[from two or more different classes] a dose equivalent to 1000mg /day
Chlorpromazine for 6 weeks.
• Consider Clozapine](https://image.slidesharecdn.com/schizophreniaandrelateddisorders20214thyears-241009161001-d101e1c9/75/Schizophrenia-and-related-disorders-2021-4th-years-pptx-27-2048.jpg)
![Catatonia Associated With Another Mental
Disorder
Diagnostic Criteria for Catatonia Associated With Another Mental Disorder (Catatonia Specifier)
A. The clinical picture is dominated by three (or more) of the following symptoms:
1. Stupor (i.e., no psychomotor activity; not actively relating to environment).
2. Catalepsy (i.e., passive induction of a posture held against gravity).
3. Waxvy flexibility (i.e., slight, even resistance to positioning by examiner).
4. Mutism (i.e., no, or very little, verbal response [exclude if known aphasia]).
5. Negativism (i.e., opposition or no response to instructions or external stimuli).
6. Posturing (i.e., spontaneous and active maintenance of a posture against gravity).
7. Mannerism (i.e., odd, circumstantial caricature of normal actions).
8. Stereotypy (i.e., repetitive, abnormally frequent, non-goal-directed movements).
9. Agitation, not influenced by external stimuli.
10. Grimacing.
11. Echolalia (i.e., mimicking another’s speech).
12. Echopraxia (i.e., mimicking another’s movements).](https://image.slidesharecdn.com/schizophreniaandrelateddisorders20214thyears-241009161001-d101e1c9/75/Schizophrenia-and-related-disorders-2021-4th-years-pptx-64-2048.jpg)
![schizophrenia_-final[1]psychiatry courses.pptx](https://cdn.slidesharecdn.com/ss_thumbnails/schizophrenia-final1-241125165758-037ddbda-thumbnail.jpg?width=640&height=640&fit=bounds)
Schizophrenia and related disorders 2021, 4th years.pptx
- 1. SCHIZOPHRENIA AND OTHERPSYCHOTIC RELATED DISORDERS BY DR. HM NDJABA MD, MMED PSYCH JANUARY, 2022
- 2. Table of contents •Introduction • Schizophrenia • Definition • Epidemiology • Etiology • Treatment • Course and prognosis • Other Psychotic disorders • Reference list PSYCHOSIS • It is inability to distinguish reality from fantasy; impaired reality testing, with the creation of a new reality • Patients find it difficult to understand what is real and what is not real ‘lost contact with reality’
- 3. • Schizophrenia andthe other psychotic disorders in this diagnostic class all share the common manifestation of psychosis. • Overall, schizophrenia and its related psychotic disorders in DSM-5 have undergone moderate changes from the DSM-IV disorders
- 4. Introduction • According toDSM 5 -It includes a spectrum of psychotic disorders that includes: • Schizophrenia • Delusional disorder • Brief psychotic disorder • Schizophreniform disorder • Schizoaffective disorder • Schizotypal personality disorder • Substance and medication related psychotic disorders • Psychotic Disorders due to a another medical condition • Catatonic disorders due to medical cause • Unspecified catatonia • Other specified Schizophrenia spectrum and other psychotic disorder • Unspecified Schizophrenia spectrum and other psychotic disorder
- 5. Schizophrenia • is achronic and often life-long disorder. • A mental disorder characterized by disintegration of thought processes and of emotional responsiveness. • The natural course is characterized by relapses, incomplete remission, increase risk of chronicity after each subsequent episode. • Cognitive deterioration, negative symptoms and social disability. • Duration – 6 months of disturbances (with at least one month of symptoms, or less if symptoms remitted with Rx)
- 6. SCHIZOPHRENIA: Definition • “schizo”- fragmented or split apart • “phrenia” - mind • Brain disorder that affects how people think, feel and perceive • Hallmark symptoms of psychosis • It is not the same as dissociative identify disorder also known as multiple personality disorder or split personality
- 7. Schizophrenia Epidemiology • Schizophreniais among the 10 leading causes of disability in the world among people in the 15-44 age, according to WHO- The Global Burden of disease • Prevalence: 0.3-0.7%, M:F = 1:1 • Mean age of onset: • females 21-30 years • males early 18-25 years
- 8. Schizophrenia: The 3phases Prodromal • This phase can last for weeks, months even years • People begin to lose interest in their usual pursuits; pull away from family and friends • May become easily confused, have trouble concentrating and feel lethargic and apathetic, prefer spending their days alone Acute • Characterized by acute psychotic episode • Patients experience both the negative and positive symptoms • The positive symptoms experienced more in this phase Residual • Symptoms similar to those of prodromal phase • Positive symptoms reduced, though negative symptoms do persist • Cognitive functioning is improved, patient is aware of their strange beliefs
- 9. Schizophrenia: Etiology Genetics • Familystudies: • siblings of patient with schizophrenia = 10% chance • one parent with schizophrenia= 5 % chance • both parents with schizophrenia= 45% chance • Twin studies • MZ twins concordance=46% • DZ twins concordance=14% • Molecular genetic studies : • Several candidate genes identified- “susceptibility” • Genes: dysbindin (Chrm 6p), neuregulin 1 (8p) and G72 (13q)
- 10. Schizophrenia Etiology Neurochemistry • Dopaminehypothesis : • Excess activity in the mesolimbic dopamine pathway may mediate the positive symptoms of psychosis • Decreased dopamine in the prefrontal cortex may mediate negative and cognitive symptoms. • Three drugs that support theory: phenothiazine's, L-dopa, illicit drugs-amphetamines, cocaine and cannabis
- 11. Etiology con. • Neuroanatomy: •Enlargement of lateral ventricles • Smaller than normal total brain volume • Cortical atrophy • Widening of third ventricle • Smaller hippocampus
- 12. Neuroendocrinology: • abnormal growthhormone, prolactin, cortisol Neuropsychology: • global defects seen in attention, language, and memory suggest disrupted connectivity of neural networks Environmental: • drug use (cannabis use), geographical variance, winter season of birth, obstetrical complications, and prenatal viral exposure
- 13. Schizophrenia: Clinical features •Positive Symptoms-Deviant Sx • Hallucinations • Delusions • Negative symptoms- Deficient Sx • Avolition • Alogia • Affect-flattened • Anhedonia • Asociality • Other symptoms: • Lack insight • Memory • Attention • Disturbances in sleep and sexual interest
- 14. Clinical Features • Cognitivesymptoms- Disorganized dimension • Thought disorder (form and content), disorganized speech • Disorganized behavior- catatonic behavior Schneider’s first rank symptoms • Delusional perception – a new delusion that forms in response to a real perception without any logical sense. • 3rd person auditory hallucination • Thought interference • Passivity phenomenon
- 15. Schizophrenia: Different types •Paranoid type -delusions and hallucinations present, no other behavior disorder • Disorganized type- thought disorder and flat affect • Catatonic type • Undifferentiated type • Residual type – positive symptoms at low intensity only ICD – 10 defines 2 additional subtypes • Post schizophrenic depression • Simple schizophrenia (prominent negative symptoms and no psychotic symptoms)
- 16. Schizophrenia- DSM VCriteria for diagnosis A. 2 or more of the following present for at least a duration of 1 /12 ( or less if successfully treated ) At least one of these must be present(1,2 or 3) 1. Delusions 2. Hallucinations particularly auditory 3. Disorganized speech 4. Disorganized or catatonic behavior 5. Negative symptoms B. Deterioration in the level of functioning at work, social relationships or with regard to self care
- 17. C. A durationof 6 months. This period must include the active phase of illness (symptoms of A) with or without a prodromal or residual phase D. Full mood syndrome (depression or mania), if present only developed after onset of psychotic symptoms or was of brief duration. E. Not the result of a general medical condition. F. if history of autism spectrum disorder or communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are also present for at least 1 mo. (or less if successfully treated).
- 18. Schizophrenia- DSM VCriteria for diagnosis • Various course specifiers are used, though only if the disorder has been present for at least 1 year and if they do not contradict diagnostic course criteria. These specifiers include the following: • First episode, • currently in acute episode • currently in partial remission • currently in full remission
- 19. • Multiple episodes, •currently in acute episode • currently in partial remission • currently in full remission • Continuous • Unspecified
- 20. Specifier- severity • Eachof the symptoms may be rated for its current severity (in the last 7 days) on a 5 point scale: • 0- not present • 1- present • 2- present and mild • 3- present and moderate • 4- present and severe
- 21. Co-morbidities • Substance-related disorders. •Anxiety disorders. • Reduced life expectancy secondary to medical comorbidities (e.g. obesity, diabetes, metabolic syndrome, CV/pulmonary disease).
- 22. Schizophrenia: Management Biological treatment •Acute treatment : • Antipsychotics: • First line- • First generation antipsychotics (haloperidol) • Second generation antipsychotics (risperidone, olanzapine,)
- 23. • Second lineClozapine • Resistant schizophrenia, useful in patients with suicidal behavior • Maintenance therapy • Initial episode- treat for 1-2 years - because of the high risk of relapse • Multiple episodes-treat for 5 years
- 24. Schizophrenia: Management Adjunctive: • Moodstabilizers (for aggression/impulsiveness - lithium, valproate, carbamazepine) • Anxiolytics (benzodiazepines) with or without ECT • Antidepressants – for depression • Electroconvulsive therapy : • Concurrent depression and catatonic symptoms
- 25. Schizophrenia: Management Psychosocial interventions: •Psychotherapy : • CBT- individual • Supportive therapy: Family and group • ACT (Assertive Community Treatment): • mobile mental health teams that provide individualized treatment in the community and help patients with medication adherence, • basic living skills, • social support, • job placements, resources
- 26. • Social skillstraining • Employment programs/ vocational rehabilitation • Disability benefits • Appropriate housing (group home, boarding home, transitional home)
- 27. Treatment resistant Schizophrenia •About up to 30% will experience persistent symptoms • Referred to as treatment resistant schizophrenia • or treatment refractory or incomplete recovery Criteria • Persistent positive symptoms and poor response to medication • No period of good functioning in preceding 5 years • Failure to respond after three periods of treatment with antipsychotics [from two or more different classes] a dose equivalent to 1000mg /day Chlorpromazine for 6 weeks. • Consider Clozapine
- 28. Schizophrenia: Course andprognosis • Suicide 5-6% • 20% will attempt suicide. • Outcome (this is variable and depends on a number of factors) • 10 % good outcome • 45 % intermediate outcome • 45 % poor outcome • Poor prognosis • family history of schizophrenia • insidious onset • early age of onset • chronic duration • assaultive, severely disorganized behavior • single • male • predominant negative features • comorbid substance abuse
- 29. Differential Diagnosis • Psychiatricdisorders • Bipolar Disorder • Major Depression with Psychotic features • Brief Psychotic disorder • Schizophreniform disorder • Schizoaffective disorder • Delusional disorder • Medical conditions • Complex Partial Seizures • Brain tumors • Trauma • CNS Infections (Syphilis, AIDS, herpetic encephalitis Huntington's disease • Porphyria • SLE
- 30. Delusional Disorder • Itscharacterized by presence of well-systemized delusions accompanied by an affect appropriate to the delusion occurring in the presence of a relatively well persevered personality • The delusions will last at least a duration of 1/12 • Behavior is not odd or bizarre apart from the delusion • No positive symptoms • No negative symptoms • Not due to a mood disorder, GMC, or substance abuse
- 31. Delusional Disorder DSM5 A. The presence of one (or more) delusions with a duration of 1 month or longer. B. Criterion A for schizophrenia has never been met. Note: Hallucinations, if present, are not prominent and are related to the delusional theme (e.g., the sensation of being infested with insects associated with delusions of infestation). C. Apart from the impact of the delusion(s) or its ramifications, functioning is not markedly impaired, and behavior is not obviously bizarre or odd. D. If manic or major depressive episodes have occurred, these have been brief relative to the duration of the delusional periods. E. The disturbance is not attributable to the physiological effects of a substance or another medical condition and is not better explained by another mental disorder, such as body dysmorphic disorder or obsessive compulsive disorder.
- 32. Delusional disorder TypesDSM 5 • Erotomanic (de Clerambault’s syndrome) • Grandiose • Jealous • Persecutory • Somatic • Mixed • Unspecified • Specify if there is bizarre content
- 33. Delusional Disorder DSM5 types • Specify : • First episode – currently in • In acute phase • Partial remission • Full remission • Multiple episodes –currently in • Acute episode • Partial remission • Full remission • Continuous • Unspecified
- 34. Delusional Disorder: Epidemiology •Prevalence 0.2 % in general population • The persecutory is the most common • No major differences in gender in frequency • A disorder of middle to late adult life • It has a significant familial relationship with schizophrenia and schizotypal personality disorder • Disorder is chronic and most people maintain occupational functioning and self care
- 35. Delusional Disorder: Clinicalfeatures • Socially isolated and chronically suspicious • Angry , hostile- emotions can lead to violent outburst • Over talkative, circumstantial
- 36. Delusional Disorder: Differentialdiagnosis • Mood disorders • Schizophrenia • Paranoid personality disorder
- 37. Delusional Disorder: Management Biologicaltreatment • Antipsychotics- Help relieve anxiety and agitation • High potency typical: Haloperidol 5-10mg/day • Sec Generation: Risperidone 2-6 mg /day • Pimozide 4-8mg • SSRI’s : Fluoxetine, paroxetine Psychosocial Approach: • Build a good doctor-patient relationship • No group therapy
- 38. Brief Psychotic Disorder •Psychotic symptoms that last at least 1 day but no more than 1/12, with gradual recovery • Psychotic mood disorders, schizophrenia, and the effects of drugs/medical conditions have been ruled out as the cause • Signs and symptoms include: • Hallucinations • Delusions • Disorganized speech • Disorganized behavior
- 39. Brief Psychotic Disorder •There are 4 subtypes: • With marked stressors • Without marked stressors • Postpartum onset • With catatonia
- 40. Brief Psychotic DisorderEpidemiology • Prevalence may be high as 9 % of new onset psychosis, and it is twice as common in women. • More common in patients with a low socioeconomic class and persons with a personality disorder ( especially borderline and schizotypal types
- 41. Brief Psychotic DisorderManagement • Hospitalization may be needed- for safety purposes • Self limiting, no specific treatment is indicated • Biological model: • Antipsychotics • Psychosocial: • Identify stressors and remove if possible • Supportive treatment- restore morale and self esteem
- 42. Schizoaffective Disorder: Epidemiology •One-third as prevalent as schizophrenia • Subtypes : • bipolar type • Depressive type • Prevalence: lifetime prevalence= 0.3% • Higher in females • Age of onset: early adulthood • Suicide Risk= 5% (lifetime)
- 43. Epidemiology Cont. Youngpeople with schizoaffective disorder tend to have bipolar subtype, whereas old people tend to have the depressive subtype. Overall the disorder affects more women than men, probably in part because more women have depressive subtype as opposed to the bipolar subtype. Men with schizoaffective disorder tend to exhibit antisocial traits and behavior in contrast to other personality traits.
- 44. In addition,the age of onset is later for women than for men. No race-based differences in frequency have been observed.
- 45. Pathophysiology The exactpathophysiology is unknown but it may involve -neurotransmitter imbalances in the brain -abnormalities of the neurotransmitters serotonin, dopamine -reduced hippocampal volumes -thalamic abnormalities -white-matter abnormalities
- 46. PATHOPHYSIOLOGY CONT Thefrequency of schizoaffective disorder worldwide is difficult to determine, because the diagnostic criteria have changed over the past few years. A Finnish study estimated the lifetime prevalence of schizoaffective disorder to be about 0,32%. A French review cited a range of 0,5- 0,8%. These numbers are only estimates, no studies have been performed.
- 47. Schizoaffective Disorder DSM-5 DiagnosticCriteria for Schizoaffective Disorder • A. concurrent psychosis (criterion A of schizophrenia) and major mood episode - uninterrupted period of illness • B. delusions or hallucinations for 2 or more wk in the absence of a major mood episode during the lifetime duration of the illness • C. major mood episode symptoms are present for the majority of the total duration of the active and residual periods of the illness • D. the disturbance is not attributable to the efects of a substance or another medical condition • specifiers: bipolar type, depressive type, with catatonia - type of episode, severity
- 48. Schizoaffective Disorder 1. Pharmacotherapy-several medications are used to treat schizoaffective disorder depends on the subtype which is present. a) In a depressive subtype- a combination of antidepressants (i.e., fluoxetine ) plus an antipsychotic (i.e., haloperidol ) are used. b) In the manic subtype – combinations of mood stabilizer ( i.e., sodium valproate ) plus an antipsychotic are used. 2. Psychotherapy and Psychoeducational programs – should include supportive therapy, assertive community therapy, individual or group form of therapy and rehabilitation programs.
- 49. Prognosis The prognosisfor patients with schizoaffective disorder is thought to lie between that of patients with schizophrenia and that of patients with mood disorder. The prognosis is better in schizoaffective disorder than that of schizophrenia alone but worse than that of a mood disorder alone.
- 50. Schizophreniform Disorder • Patientspresent with symptoms typical for schizophrenia but for a duration less than 6/ 12
- 51. DSM V Schizophreniform Criteriafor diagnosis A. At least two or more of the following • Delusions • Hallucinations particularly auditory • Disorganized speech • Disorganized or catatonic behavior • Negative symptoms D. Full mood syndrome (depression or mania), if present only developed after onset of psychotic symptoms or was of brief duration E. Not the result of a general medical condition
- 52. Schizophreniform: Epidemiology • Lifetimeprevalence of schizophreniform disorder is approximately 0.2% • Prevalence is the same in males and females. • Depressive symptoms commonly coexist and are associated with an increased suicide risk
- 53. Schizophreniform: Course andprognosis • 60 – 80% progress to scp • Some pt will have a 2nd or 3rd episode during which they deteriorate into more chronic hence scp ( bad prognosis) • Few patients may just have a single episode and continue with their lives (good prognosis)
- 54. Schizophreniform: Management • Hospitalizationfor effective assessment, Rx and supervision of pt behavior • Biological • Give antipsychotic medication 3 to 6 months ( response is rapid as compared to scp) • Mood stabilizers can be used • Psychotherapy – help pt integrate the psychosis experience into their understanding of their own minds and lives • ECT for some eg marked catatonia or depressed features.
- 55. Substance/Medication Induced PsychoticDisorder • Presence of hallucination and/or delusions (criterion A) • Evidence in history, examination or lab results (criterion B) * • Not better explained by psychotic disorder that is drug induced (criterion C)* • Not exclusive during delirium (criterion D) and impairment in functioning (criterion E)
- 56. TREATMENT • Antipsychotics: FGAvs SGA • Antidepressants • Benzodiazepines
- 57. Schizotypal Personality Disorder •Is a pattern of acute discomfort in close relationships, cognitive or perceptual distortions, and eccentricities of behavior. • A pattern of detachment from social relationships and a restricted range of emotional expression overlaps with Asperger’sHigh Functioning Autism’ • Prevalence: 2-3% • M>F
- 58.
- 59. Schizotypal Personality DisorderDSM 5 Diagnostic Criteria
- 60. Schizotypal Personality DisorderDSM 5 Diagnostic Criteria
- 61. Schizotypal Personality Management •Treatment is based individual needs: • Social skills Training: • Awareness of odd behavior , enable them to establish relationships • Biological treatment: • Antipsychotics – intense a anxiety, paranoia,
- 62. Substance/Medication-Induced Psychotic Disorder Diagnostic Criteriafor Substance/Medication-Induced Psychotic Disorder A. Presence of one or both of the following symptoms: 1. Delusions. 2. Hallucinations. B. There is evidence from the history, physical examination, or laboratory findings of both (1) and (2): 1. The symptoms in Criterion A developed during or soon after substance intoxication or withdrawal or after exposure to a medication. 2. The involved substance/medication is capable of producing the symptoms in Criterion A. C. The disturbance is not better explained by a psychotic disorder that is not substance/medication-induced. Such evidence of an independent psychotic disorder could include the following: The symptoms preceded the onset of the substance/medication use; the symptoms persist for a substantial period of time (e.g., about 1 month) after the cessation of acute withdrawal or severe intoxication; or there is other evidence of an independent non- substance/medication-induced psychotic disorder (e.g., a history of recurrent non-substance/medication-related episodes). D. The disturbance does not occur exclusively during the course of a delirium. E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- 63. Psychotic Disorder Dueto a Another Medical Condition Diagnostic Criteria for Psychotic Disorder Due to a Another Medical Condition A. Prominent hallucinations or delusions. B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition. C. The disturbance is not better explained by another mental disorder. D. The disturbance does not occur exclusively during the course of a delirium. E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- 64. Catatonia Associated WithAnother Mental Disorder Diagnostic Criteria for Catatonia Associated With Another Mental Disorder (Catatonia Specifier) A. The clinical picture is dominated by three (or more) of the following symptoms: 1. Stupor (i.e., no psychomotor activity; not actively relating to environment). 2. Catalepsy (i.e., passive induction of a posture held against gravity). 3. Waxvy flexibility (i.e., slight, even resistance to positioning by examiner). 4. Mutism (i.e., no, or very little, verbal response [exclude if known aphasia]). 5. Negativism (i.e., opposition or no response to instructions or external stimuli). 6. Posturing (i.e., spontaneous and active maintenance of a posture against gravity). 7. Mannerism (i.e., odd, circumstantial caricature of normal actions). 8. Stereotypy (i.e., repetitive, abnormally frequent, non-goal-directed movements). 9. Agitation, not influenced by external stimuli. 10. Grimacing. 11. Echolalia (i.e., mimicking another’s speech). 12. Echopraxia (i.e., mimicking another’s movements).
- 65. B. There isevidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition. C. The disturbance is not better explained by another mental disorder (e.g., a manic episode). D. The disturbance does not occur exclusively during the course of a delirium. E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- 66. Other Specified SchizophreniaSpectrum and Other Psychotic Disorder and Unspecified These are residual categories for individuals whose symptoms do not fit within one of the more specific categories. The categories replace DSM-IV’s psychotic disorder not otherwise specified. Other specified schizophrenia spectrum and other psychotic disorder can be used in situations in which an individual has symptoms characteristic of a spectrum disorder that cause distress or impairment but that do not meet full criteria for a more specific disorder. In this case, the clinician chooses to communicate the reason that individual’s symptoms do not meet the criteria. The category unspecified schizophrenia spectrum and other psychotic disorder is used when the clinician chooses not to specify the reason that criteria are not met for a more specific disorder, or when there is insufficient information to make a more specific diagnosis
- 67. Examples of presentationsthat can be specified using the “other specified” designation include the following: 1. Persistent auditory hallucinations occurring in the absence of any other features. 2. Delusions with significant overlapping mood episodes: This includes persistent delusions with periods of overlapping mood episodes that are present for a substantial portion of the delusional disturbance (such that the criterion stipulating only brief mood disturbance in delusional disorder is not met). 3. Attenuated psychosis syndrome: This syndrome is characterized by psychotic like symptoms that are below a threshold for full psychosis (e.g., the symptoms are less severe and more transient, and insight is relatively maintained). 4. Delusional symptoms in partner of individual with delusional disorder: In the context of a relationship, the delusional material from the dominant partner provides content for delusional belief by the individual who may not otherwise entirely meet criteria for delusional disorder.
- 68. TAKE HOME MESSAGE •SchizophreniaSpectrum and Other Psychotic Disorders have high morbidity and mortality rates. •A many modules have been formulated over the years to assist in the differentiation of these various psychotic disorders. i.e. DSM -5, ICD •Antipsychotics are cornerstone, but treatment must always be individualized.
- 69.
Editor's Notes
- #39 Patients with postpartum onset generally develop symptoms during pregnancy or within 4 weeks after delivery. Postpartum psychosis, as it is often called, tends to arise in otherwise normal individuals and resolves within 2–3 months. The disorder should be distinguished from postpartum blues, which occurs in up to 80% of new mothers, lasts for a few days after delivery, and is considered normal.