ANTIDEPRESSANT

DRUGS
LEVEL 4
19.07.2023
8-9 am
INTRODUCTION-WHAT ARE ANTIDEPRESSANTS

 ANTIDEPRESSANTS ARE A TYPE OF MEDICATION USED TO TREAT

CLINICAL DEPRESSION OR PREVENT IT FROM COMING BACK.
 IT REFERS TO A GROUP OF DRUGS THAT WORK ON THE CHEMICALS
IN OUR BRAINS CALLED NEUROTRANSMITTERS.
 ANTIDEPRESSANTS HELP BY RESTORING THE BALANCE OF THESE
CHEMICALS.
 AN ANTIDEPRESSANT, AS THE NAME IMPLIES, IS A TYPE OF DRUG
PRIMARILY USED FOR THE TREATMENT OF DEPRESSION.
 DEPRESSION IS A COMMON DISORDER THAT AFFECTS THE
CHEMISTRY AND FUNCTION OF BRAIN. ANTIDEPRESSANTS CAN HELP
CORRECT THE DYSFUNCTION BY ALTERING THE CIRCUITS AND
CHEMICALS THAT PASS SIGNALS ALONG NERVE ROUTES TO THE
BRAIN.
INTRODUCTION

 ANTIDEPRESSANTS ARE GROUPED INTO CLASSES BASED ON HOW

THEY AFFECT THE CHEMISTRY OF THE BRAIN.
 WHILE THE ANTIDEPRESSANTS IN A CLASS WILL TEND TO HAVE
SIMILAR SIDE EFFECTS AND MECHANISM OF ACTION , THERE ARE
DIFFERENCES IN THEIR MOLECULAR STRUCTURES WHICH CAN
INFLUENCE HOW WELL THE DRUG IS ABSORBED, DISSEMINATED, OR
TOLERATED IN DIFFERENT PEOPLE.
 THERE ARE FIVE MAJOR CLASSES OF ANTIDEPRESSANT AND SEVERAL
OTHERS THAT ARE LESS COMMONLY USED.
ANTIDEPRESSANT DRUGS
CLASSIFICATION

 I. MONOAMINE OXIDASE( MAO ) INHIBITORS .

 MAO IS A MITOCHONDRIAL ENZYME INVOLVED IN THE OXIDATIVE
DEAMINATION OF BIOGENIC AMINES (ADR,
adrenaline NA
noradrenaline, DA dopamine, 5HT 5
hydroxytryptamine).
 II. TRICYCLIC ANTIDEPRESSANTS (TCAS)
 III. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS)

 IV. ATYPICAL ANTIDEPRESSANTS

 V. SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS)

II. TRICYCLIC ANTIDEPRESSANTS
(TCAS)


A. NA + 5HT REUPTAKE INHIBITORS
 IMIPRAMINE,
 AMITRIPTYLINE,
 TRIMIPRAMINE,
 DOXEPIN,
 DOTHIEPIN,
 CLOMIPRAMINE




TRICYCLIC ANTIDEPRESSANTS
(TCAS)
 B. PREDOMINANTLY NA REUPTAKE INHIBITORS
 DESIPRAMINE,
 NORTRIPTYLINE,
 AMOXAPINE,
 REBOXETINE
HISTORY OF TCA

 IMIPRAMINE, AN ANALOGUE OF CHLOROPROMAZINE (CPZ) WAS

FOUND DURING CLINICAL TRIALS (1958) TO SELECTIVELY BENEFIT
DEPRESSED BUT NOT AGITATED PSYCHOTICS.
 IN CONTRAST TO CPZ, IT INHIBITED NA AND 5HT REUPTAKE INTO
NEURONES.
 A LARGE NUMBER OF CONGENERS WERE SOON ADDED AND ARE
COLLECTIVELY CALLED TRICYCLIC ANTIDEPRESSANTS (TCAS).
 ACTION OF TCAS

 THE MOST PROMINENT ACTION OF TCAS IS THEIR ABILITY TO INHIBIT

NOREPINEPHRINE TRANSPORTER (NET) AND SEROTONIN
TRANSPORTER (SERT) LOCATED AT NEURONAL/PLATELET MEMBRANE
AT LOW AND THERAPEUTICALLY ATTAINED CONCENTRATIONS.
 THE TCAS INHIBIT
 MONOAMINE REUPTAKE
 AND INTERACT WITH A VARIETY OF
RECEPTORS VIZ. MUSCARINIC, Α ADRENERGIC, HISTAMINE H1, 5HT1, 5
HT2 AND OCCASIONALLY DOPAMINE D2.
 THE NEWER SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS) AND
ATYPICAL ANTIDEPRESSANTS INTERACT WITH FEWER RECEPTORS AND
HAVE MORE LIMITED SPECTRUM OF ACTION (PRODUCE FEWER SIDE
EFFECTS). THE ACTIONS OF IMIPRAMINE ARE DESCRIBED AS PROTOTYPE.
EFFECTS IN 1. CNS

 EFFECTS DIFFER IN NORMAL INDIVIDUALS AND THE DEPRESSED.

 IN NORMAL INDIVIDUALS IT INDUCES
 A PECULIAR CLUMSY FEELING,
 TIREDNESS,
 LIGHT-HEADEDNESS,
 SLEEPINESS,
 DIFFICULTY IN CONCENTRATING AND THINKING,
 UNSTEADY GAIT.

THESE EFFECTS TEND TO PROVOKE ANXIETY. THERE IS NO MOOD

ELEVATION OR EUPHORIA; EFFECTS ARE RATHER UNPLEASANT AND
MAY BECOME MORE SO ON REPEATED ADMINISTRATION.


EFFECTS IN 1. CNS

 IN DEPRESSED PATIENTS LITTLE ACUTE EFFECTS ARE PRODUCED, EXCEPT

SEDATION (IN THE CASE OF DRUGS WHICH HAVE SEDATIVE PROPERTY).
 AFTER 2–3 WEEKS OF CONTINUOUS TREATMENT, THE MOOD IS GRADUALLY
ELEVATED, PATIENTS BECOME MORE COMMUNICATIVE AND START TAKING
INTEREST IN SELF AND SURROUNDINGS.
 THUS, TCAS ARE NOT EUPHORIENTS BUT ONLY ANTIDEPRESSANTS. IN DEPRESSED
PATIENTS WHO HAVE PREPONDERANCE OF REM SLEEP, THIS PHASE IS SUPPRESSED
AND AWAKENINGS DURING NIGHT ARE REDUCED.
 THE EEG EFFECTS OF LOW DOSES ARE SIMILAR TO HYPNOTICS BUT HIGH DOSES
CAUSE DESYNCHRONIZATION.
 SEDATIVE PROPERTY VARIES AMONG DIFFERENT COMPOUNDS:
 THE MORE SEDATIVE ONES ARE SUITABLE FOR DEPRESSED PATIENTS SHOWING
ANXIETY AND AGITATION. THE LESS SEDATIVE OR STIMULANT ONES ARE BETTER
FOR WITHDRAWN AND RETARDED PATIENTS.
MECHANISM OF ACTION tcas

 INHIBIT ACTIVE REUPTAKE OF

THE TCAS AND RELATED DRUGS
BIOGENIC AMINES NA AND 5HT INTO THEIR RESPECTIVE NEURONES AND
THUS POTENTIATE THEM. THEY, HOWEVER, DIFFER MARKEDLY IN THEIR
SELECTIVITY AND POTENCY FOR DIFFERENT AMINES
 REUPTAKE INHIBITION RESULTS IN INCREASED CONCENTRATION OF THE AMINES
IN THE SYNAPTIC CLEFT IN THE CNS AND PERIPHERY.
 TENTATIVE CONCLUSIONS DRAWN ARE:
 INHIBITION OF DA UPTAKE CORRELATES WITH STIMULANT ACTION; BUT IS
NOT PRIMARILY INVOLVED IN ANTIDEPRESSANT ACTION.
 • INHIBITION OF NA AND 5HT UPTAKE IS ASSOCIATED WITH ANTIDEPRESSANT
ACTION.

SHORT-TERM ADMINISTRATION

 SEVERAL FINDINGS INDICATE THAT UPTAKE BLOCKADE IS NOT

DIRECTLY RESPONSIBLE FOR ANTIDEPRESSANT ACTION,
 E.G. UPTAKE BLOCKADE OCCURS QUICKLY BUT ANTIDEPRESSANT
ACTION DEVELOPS AFTER WEEKS;
 MIANSERIN IS ANTIDEPRESSANT BUT HAS NO UPTAKE BLOCKING
ACTION. INITIALLY THE PRESYNAPTIC Α2 AND 5HT1 AUTORECEPTORS
ARE ACTIVATED BY THE INCREASED AMOUNT OF NA/5HT IN THE
SYNAPTIC CLEFT RESULTING IN DECREASED FIRING OF LOCUS
COERULEUS (NORADRENERGIC) AND RAPHE (SEROTONERGIC)
NEURONES.
LONG-TERM ADMINISTRATION

 HOWEVER, ON LONG-TERM ADMINISTRATION, ANTIDEPRESSANTS

DESENSITISE PRESYNAPTIC Α2, 5HT1A, 5HT1D AUTORECEPTORS AND
INDUCE OTHER ADAPTIVE CHANGES IN THE NUMBER AND
SENSITIVITY OF PRE AND POST SYNAPTIC NA AND/OR 5HT
RECEPTORS AS WELL AS IN AMINE TURNOVER OF BRAIN,
 THE NET EFFECT OF WHICH IS ENHANCED NORADRENERGIC AND
SEROTONERGIC TRANSMISSION. THUS,
 UPTAKE BLOCKADE APPEARS TO INITIATE A SERIES OF TIME-
DEPENDENT CHANGES THAT CULMINATE IN ANTIDEPRESSANT
EFFECT.
TCA EFFECTS ON AUTONOMIC
SYSTEM

 MOST TCAS ARE POTENT ANTICHOLINERGICS—CAUSE DRY MOUTH,

BLURRING OF VISION, CONSTIPATION AND URINARY HESITANCY AS
SIDE EFFECT.

 THEY POTENTIATE EXOGENOUS AND ENDOGENOUS NA BY BLOCKING

UPTAKE, BUT ALSO HAVE WEAK Α1 ADRENERGIC BLOCKING ACTION.
SOME, E.G. AMITRIPTYLINE, DOXEPIN, TRIMIPRAMINE HAVE SLIGHT
H1 ANTIHISTAMINIC ACTION AS WELL.
3. TCA EFFECTS ON CVS

 3. TCA EFFECTS ON CARDIOVASCULAR FUNCTION ARE PROMINENT, OCCUR AT

THERAPEUTIC CONCENTRATIONS AND MAY BE DANGEROUS IN OVERDOSE.

 TACHYCARDIA: DUE TO ANTICHOLINERGIC AND NA POTENTIATING ACTIONS.

 POSTURAL HYPOTENSION: DUE TO INHIBITION OF CARDIOVASCULAR REFLEXES
AND Α1 BLOCKADE.

 ECG CHANGES AND CARDIAC ARRHYTHMIAS:

 T WAVE SUPPRESSION OR INVERSION IS THE MOST CONSISTENT CHANGE.
 ARRHYTHMIAS OCCUR IN OVERDOSE DUE TO INTERFERENCE WITH INTRAVENTRICULAR
CONDUCTION, COMBINATION OF NA POTENTIATING + ACH BLOCKING ACTIONS AND DIRECT
MYOCARDIAL DEPRESSION.
 OLDER PATIENTS ARE MORE SUSCEPTIBLE. THE SSRIS AND ATYPICAL ANTIDEPRESSANTS ARE
SAFER IN THIS REGARD.

TCAs INTERACTIONS- CHEESE
REACTION

 THESE DRUGS INHIBIT A NUMBER OF OTHER ENZYMES AS WELL, AND

INTERACT WITH MANY FOOD CONSTITUENTS AND DRUGS.

 1. CHEESE REACTION
 CERTAIN VARIETIES OF CHEESE, BEER, WINES, PICKLED MEAT AND FISH,
YEAST EXTRACT CONTAIN LARGE QUANTITIES OF TYRAMINE, DOPA, ETC.
 IN MAO INHIBITED PATIENTS THESE INDIRECTLY ACTING
SYMPATHOMIMETIC AMINES ESCAPE DEGRADATION IN THE INTESTINAL
WALL AND LIVER → REACHING INTO SYSTEMIC CIRCULATION
 THEY DISPLACE LARGE AMOUNTS OF NA FROM TRANSMITTER LOADED
ADRENERGIC NERVE ENDINGS → HYPERTENSIVE CRISIS,
CEREBROVASCULAR ACCIDENTS. WHEN SUCH A REACTION OCCURS, IT
CAN BE TREATED BY I.V. INJECTION OF A RAPIDLY ACTING Α BLOCKER,
E.G. PHENTOLAMINE. PRAZOSIN OR CHLORPROMAZINE ARE
ALTERNATIVES.

TCA - DEPENDENCE

 PSYCHOLOGICAL DEPENDENCE ON THESE DRUGS IS RARE, BECAUSE

THEIR ACUTE EFFECTS ARE NOT PLEASANT.


 THERE IS SOME EVIDENCE OF PHYSICAL DEPENDENCE OCCURRING

WHEN HIGH DOSES ARE USED FOR LONG PERIODS—
 MALAISE,
 CHILLS,
 MUSCLE PAIN MAY OCCUR ON DISCONTINUATION AND HAVE BEEN
CONSIDERED WITHDRAWAL PHENOMENA.
 GRADUAL WITHDRAWAL IS RECOMMENDED, BUT
ANTIDEPRESSANTS DO NOT CARRY ABUSE POTENTIAL.
PHARMACOKINETICS

 THE ORAL ABSORPTION OF TCAS IS GOOD, THOUGH OFTEN SLOW.

 THEY ARE HIGHLY BOUND TO PLASMA AND TISSUE PROTEINS—HAVE LARGE
VOLUMES OF DISTRIBUTION (~20 L/KG).
 THEY ARE EXTENSIVELY METABOLIZED IN LIVER;
 THE MAJOR ROUTE FOR IMIPRAMINE AND AMITRIPTYLINE IS DEMETHYLATION
WHEREBY ACTIVE METABOLITES—DESIPRAMINE AND NORTRIPTYLINE
RESPECTIVELY ARE FORMED.
 FEW OTHERS ALSO PRODUCE ACTIVE METABOLITES.
 INACTIVATION OCCURS BY OX
 IDATION AND GLUCURONIDE CONJUGATION. VARIOUS CYP ISOENZYMES LIKE
CYP2D6, CYP 3A4, CYP 1A2 AND OTHERS METABOLISE TRICYLIC AND RELATED
ANTI-DEPRESSANTS. METABOLITES ARE EXCRETED IN URINE OVER 1–2 WEEKS.
THERAPEUTIC WINDOW

 AN UNUSUAL THERAPEUTIC WINDOW PHENOMENON HAS BEEN

OBSERVED,
 I.E. OPTIMAL ANTIDEPRESSANT EFFECT IS EXERTED AT A NARROW
BAND OF PLASMA CONCENTRATIONS (BETWEEN 50–200 NG/ML OF
IMIPRAMINE, AMITRIPTYLINE, NORTRIPTYLINE).
 BOTH BELOW AND ABOVE THIS RANGE, BENEFICIAL EFFECTS ARE
SUBOPTIMAL.
ADVERSE EFFECTS

 SIDE EFFECTS ARE COMMON WITH TRICYCLIC ANTIDEPRESSANTS.

 • 1. ANTICHOLINERGIC: DRY MOUTH, BAD TASTE, CONSTIPATION, EPIGASTRIC DISTRESS,

URINARY RETENTION (ESPECIALLY IN MALES WITH ENLARGED PROSTATE), BLURRED VISION, PALPITATION.

 • 2. SEDATION, MENTAL CONFUSION AND WEAKNESS, ESPECIALLY WITH AMITRIPTYLINE AND MORE
SEDATIVE CONGENERS.

 • 2. INCREASED APPETITE AND WEIGHT GAIN IS NOTED WITH MOST TCAS AND TRAZODONE,
BUT NOT WITH SSRIS AND BUPROPION.
 3.• SOME PATIENTS RECEIVING ANY ANTIDEPRESSANT MAY ABRUPTLY SWITCH OVER TO A
DYSPHORIC AGITATED STATE OR TO MANIA. MOST LIKELY, THESE ARE CASES OF BIPOLAR
DEPRESSION, THE OTHER POLE BEING UNMASKED BY THE ANTIDEPRESSANT. PATIENTS RECEIVING
HIGHER DOSES AND TCAS ARE AT GREATER RISK THAN THOSE RECEIVING LOWER DOSES AND SSRIS OR
BUPROPION.
ADVERSE EFFECTS

4. SWEATING AND FINE TREMORS ARE RELATIVELY COMMON.

5. SEIZURE THRESHOLD IS LOWERED—FITS MAY BE PRECIPITATED, ESPECIALLY IN CHILDREN.

BUPROPION, MAPROTILINE, CLOMIPRAMINE, AMOXAPINE HAVE GREATER PROPENSITY, WHILE
DESIPRAMINE AND SSRIS ARE SAFER IN THIS REGARD.


6. POSTURAL HYPOTENSION, ESPECIALLY IN OLDER PATIENTS; LESS SEVERE WITH DESIPRAMINE-

LIKE DRUGS AND INSIGNIFICANT WITH SSRIS.

5. CARDIAC ARRHYTHMIAS, ESPECIALLY IN PATIENTS WITH ISCHAEMIC HEART DISEASE—MAY

BE RESPONSIBLE FOR SUDDEN DEATH IN THESE PATIENTS. AMITRIPTYLINE AND DOSULPIN ARE
PARTICULARLY DANGEROUS IN OVERDOSE; HIGHER INCIDENCE OF ARRHYTHMIAS IS REPORTED.


6.RASHES AND JAUNDICE DUE TO HYPERSENSITIVITY ARE RARE. MIANSERIN IS MORE

HEPATOTOXIC.
TREATMENT OF SIDE EFFECTS

 TREATMENT IS PRIMARILY SUPPORTIVE WITH GASTRIC LAVAGE, RESPIRATORY

SUPPORT, FLUID INFUSION, MAINTENANCE OF BP AND BODY TEMPERATURE.
ACIDOSIS MUST BE CORRECTED BY BICARBONATE INFUSION.


 DIAZEPAM MAY BE INJECTED I.V. TO CONTROL CONVULSIONS AND DELIRIUM.

 MOST IMPORTANT IS THE TREATMENT OF CARDIAC ARRHYTHMIAS, FOR WHICH
PROPRANOLOL/LIDOCAINE MAY BE USED; CLASS IA AND IC ANTIARRHYTHMICS
AND DIGOXIN PROLONG CARDIAC CONDUCTION—ARE CONTRAINDICATED.
 PHYSOSTIGMINE (0.5–2 MG I.V.) REVERSES MANY CENTRAL AND PERIPHERAL
ANTICHOLINERGIC AND SOMETIMES CARDIAC EFFECTS. HOWEVER, IT IS
SELDOM USED SINCE ARRHYTHMIAS ARE OCCASIONALLY WORSENED AND
HYPOTENSION ACCENTUATED BY THIS TREATMENT.
INTERACTIONS

 TCAS POTENTIATE DIRECTLY ACTING SYMPATHOMIMETIC AMINES (IN COLD/ASTHMA

REMEDIES). ADRENALINE CONTAINING LOCAL ANAESTHETIC SHOULD BE AVOIDED. HOWEVER
TCAS ATTENUATE THE ACTIONS OF INDIRECT SYMPATHOMIMETICS (EPHEDRINE, TYRAMINE).

 TCAS ABOLISH THE ANTIHYPERTENSIVE ACTION OF GUANETHIDINE AND CLONIDINE BY

PREVENTING THEIR TRANSPORT INTO ADRENERGIC NEURONES.

 TCAS POTENTIATE CNS DEPRESSANTS, INCLUDING ALCOHOL AND ANTIHISTAMINICS.

 PHENYTOIN, PHENYLBUTAZONE, ASPIRIN AND CPZ CAN DISPLACE TCAS FROM PROTEIN
BINDING SITES AND CAUSE TOXICITY.
·
INTERACTIONS

 PHENOBARBITONE INDUCES AS WELL AS COMPETITIVELY INHIBITS IMIPRAMINE METABOLISM.

 · CARBAMAZEPINE AND OTHER ENZYME INDUCERS ENHANCE METABOLISM OF TCAS.

 · SSRIS INHIBIT METABOLISM OF SEVERAL DRUGS INCLUDING TCAS—DANGEROUS TOXICITY

CAN OCCUR IF THE TWO ARE GIVEN CONCURRENTLY.

 · BY THEIR ANTICHOLINERGIC PROPERTY, TCAS DELAY GASTRIC EMPTYING AND RETARD

THEIR OWN AS WELL AS OTHER DRUG’S ABSORPTION.
HOWEVER, DIGOXIN AND TETRACYCLINES MAY BE MORE COMPLETELY ABSORBED. WHEN
USED TOGETHER, THE ANTICHOLINERGIC ACTION OF NEUROLEPTICS AND TCAS MAY ADD UP.

 · MAO INHIBITORS—DANGEROUS HYPERTENSIVE CRISIS WITH EXCITEMENT AND

HALLUCINATIONS HAS OCCURRED WHEN GIVEN WITH TCAS.
THE MAJOR LIMITATIONS OF CONVENTIONAL TCAS ARE:

 FREQUENT ANTICHOLINERGIC, CARDIOVASCULAR AND

NEUROLOGICAL SIDE EFFECTS.
 RELATIVELY LOW SAFETY MARGIN, HAZARDOUS IN OVERDOSE;
FATALITIES COMMON.
 LAG TIME OF 2–4 WEEKS BEFORE ANTIDEPRESSANT ACTION
MANIFESTS.
 SIGNIFICANT NUMBER OF PATIENTS RESPOND INCOMPLETELY AND
SOME DO NOT RESPOND.
2.SELECTIVE SEROTONIN REUPTAKE
INHIBITORS (SSRIS)

 DEVELOPED SINCE 1980S.

 THESE NEWER DRUGS HAVE IMPROVED TOLERABILITY, BOTH IN
THERAPEUTIC USE AS WELL AS IN OVERDOSE.
 SAFETY AND BETTER ACCEPTABILITY OF SSRIS
 USE IN ANXIETY, PHOBIAS, OCD AND RELATED DISORDERS.
 BECAUSE OF FREEDOM FROM PSYCHOMOTOR AND COGNITIVE
IMPAIRMENT, SSRIS ARE PREFERRED FOR PROPHYLAXIS OF
RECURRENT DEPRESSION.
2. SELECTIVE SEROTONIN
REUPTAKE INHIBITORS (SSRIS)

 EXAPMPLES
 FLUOXETINE,
 FLUVOXAMINE,
 PAROXETINE,
 SERTRALINE,(ZOLOFT)
 CITALOPRAM,
 ESCITALOPRAM

WHY (SSRIS)

 DO NOT INTERFERE WITH

 COGNITIVE AND PSYCHOMOTOR FUNCTION
 OR PRODUCE ANTICHOLINERGIC SIDE EFFECTS.

 THEY ARE DEVOID OF Α

 ADRENERGIC BLOCKING ACTION—POSTURAL HYPOTENSION DOES NOT OCCUR
—SUITABLE FOR ELDERLY PATIENTS.
 THEY HAVE PRACTICALLY NO SEIZURE PRECIPITATING PROPENSITY AND DO NOT
INHIBIT CARDIAC CONDUCTION—
 SIDE EFFECTS

 GASTROINTESTINAL; ALL SSRIS FREQUENTLY PRODUCE NAUSEA (DUE TO 5HT 3 RECEPTOR

STIMULATION), BUT TOLERANCE DEVELOPS OVER TIME.
 WEIGHT GAIN IS NOT A PROBLEM WITH SSRIS,
 BUT THEY MORE COMMONLY INTERFERE WITH EJACULATION OR ORGASM.
 A NEW CONSTELLATION OF MILD SIDE EFFECTS, VIZ.
 NERVOUSNESS,
 RESTLESSNESS,
 INSOMNIA,
 ANOREXIA,
 DYSKINESIA,
 HEADACHE
 INCREASED INCIDENCE OF EPISTAXIS AND ECCHYMOSIS HAS BEEN REPORTED, PROBABLY DUE TO
IMPAIRMENT OF PLATELET FUNCTION. GASTRIC BLOOD LOSS DUE TO NSAIDS MAY BE INCREASED BY
SSRIS.

OTHER USES OF SSRIS

 THE SSRIS ARE NOW 1ST CHOICE DRUGS FOR

 OCD,
 PANIC DISORDER,
 SOCIAL PHOBIA,
 EATING DISORDERS,
 PREMENSTRUAL DYSPHORIC DISORDER
 AND POST TRAUMATIC STRESS DISORDER.
 THEY ARE ALSO BEING INCREASINGLY USED FOR MANY ANXIETY DISORDERS,
 BODY DYSMORPHIC DISORDER,
 COMPULSIVE BUYING AND KLEPTOMANIA.
ATYPICAL ANTIDEPRESSANTS

 Typical antidepressants like

 selective serotonin reuptake inhibitors or
 tricyclic antidepressants work by increasing the
levels of serotonin and norepinephrine,

 while atypical antidepressants often have

multiple mechanisms of action.
3. ATYPICAL ANTIDEPRESSANTS

 TRAZODONE 50mg ,(serotonin antagonist and reuptake inhibitor SARI) it a

serotonin modulator,causes sedation intially
 MIANSERIN,30mg (SECOND GENERATION SEROTONERGIC NORADRENERGIC)
 MIRTAZAPINE,15 MG tetracyclic antidepressants
 VENLAFAXINE,effexor SSNRIs selective serotonin and norepinephrine
reuptake inhibitors(150mg 75 mg 37.5 mg)
 DULOXETINE, 3omg cymbalta tabs SNRI serotonin norepinephrine
reuptake inhibitor(less tha 120mg/day)
 TIANEPTINE, i.e stablon tabs 12.5mg tabs tds
 AMINEPTINE TCA,dopimine and to lessor extent noerepinephrine reuptake
inhibitor
 BUPROPION Wellbutrin tabs ( NDRI) dopaminenorepinephrine reuptake
inhibitorNDRI
 VALDOXAN agomelantine 25 mg tabs up to 50mg nocte melatonin agonist.
resynchronization of sleep-wake cycle disturbed in depression,



ATYPICAL ANTIDEPRESSANTS- TRAZODONE

 IT IS THE FIRST ATYPICAL ANTIDEPRESSANT;

 SELECTIVELY BUT LESS EFFICIENTLY BLOCKS 5HT UPTAKE AND HAS
PROMINENT Α BLOCKING AS WELL AS WEAK 5HT2 ANTAGONISTIC
ACTION.
 THE LATTER MAY CONTRIBUTE TO ITS ANTIDEPRESSANT EFFECT
ATYPICAL ANTIDEPRESSANTS
MIANSERIN

 IT IS UNIQUE IN NOT INHIBITING EITHER NA OR 5HT UPTAKE;

 BUT BLOCKS PRESYNAPTIC Α2 RECEPTORS—INCREASES RELEASE AND
TURNOVER OF NA IN BRAIN WHICH MAY BE RESPONSIBLE FOR
ANTIDEPRESSANT EFFECT.
 ANTAGONISTIC ACTION AT 5HT2, 5HT1C AS WELL AS H1 RECEPTORS
HAS ALSO BEEN SHOWN.
 IT IS A SEDATIVE—RELIEVES ASSOCIATED ANXIETY AND SUPPRESSES
PANIC ATTACKS.
ATYPICAL ANTIDEPRESSANTS

 TIANEPTINE


 THIS ANTIDEPRESSANT IS REPORTED TO INCREASE RATHER THAN

INHIBIT 5HT UPTAKE, AND IS NEITHER SEDATIVE NOR STIMULANT. IT
HAS SHOWN EFFICACY IN ANXIO-DEPRESSIVE STATES, PARTICULARLY
WITH PSYCHOSOMATIC SYMPTOMS, AS WELL AS IN ENDOGENOUS
DEPRESSION.
 DOSE: 12.5 MG BD–TDS; STABLON 12.5 MG TAB.
ATYPICAL ANTIDEPRESSANTS

 AMINEPTINE


 LIKE TIANEPTINE IT ENHANCES 5HT UPTAKE, BUT HAS

ANTIDEPRESSANT PROPERTY. IT PRODUCES ANTICHOLINERGIC SIDE
EFFECTS INCLUDING TACHYCARDIA, CONFUSION AND DELIRIUM.
POSTURAL HYPOTENSION, CONDUCTION DISTURBANCES AND
ARRHYTHMIAS CAN OCCUR, ESPECIALLY IN PATIENTS WITH HEART
DISEASE.


 DOSE: 100 MG BD AT BREAKFAST AND LUNCH. NO.



 SURVECTOR 100 MG TAB.

4.ATYPICAL ANTIDEPRESSANTS
VENLAFAXINE

 A NOVEL ANTIDEPRESSANT REFERRED TO AS ‘SEROTONIN AND

NORADRENALINE REUPTAKE INHIBITOR’ (SNRI), BECAUSE IT INHIBITS
UPTAKE OF BOTH THESE AMINES BUT, IN CONTRAST TO OLDER TCAS, DOES
NOT INTERACT WITH CHOLINERGIC, ADRENERGIC OR HISTAMINERGIC
RECEPTORS OR HAVE SEDATIVE PROPERTY.
 TRIALS HAVE SHOWN IT TO BE AS EFFECTIVE ANTIDEPRESSANT AS TCAS
AND MAY WORK IN SOME RESISTANT CASES.
 A FASTER ONSET OF ACTION HAS ALSO BEEN INDICATED.
 VENLAFAXINE DOES NOT PRODUCE THE USUAL SIDE EFFECTS OF TCAS;
TENDS TO RAISE RATHER THAN DEPRESS BP AND IS SAFER IN OVERDOSE.
 PROMINENT SIDE EFFECTS ARE NAUSEA, SWEATING, ANXIETY, DIZZINESS
AND IMPOTENCE.
ATYPICAL ANTIDEPRESSANTS
DULOXETINE

 A NEWER SNRI SIMILAR TO VENLAFAXINE.

 IT IS NEITHER SEDATIVE, NOR ANTICHOLINERGIC, NOR ANTIHISTAMINIC,
NOR Α BLOCKER.
 SIDE EFFECTS, INCLUDING G.I. AND SEXUAL PROBLEMS ARE MILDER,
 BUT SOME AGITATION, INSOMNIA AND RISE IN BP CAN OCCUR.
 ANTIDEPRESSANT EFFICACY IS COMPARABLE TO TCAS AND DULOXETINE IS
ALSO INDICATED IN PANIC ATTACKS, DIABETIC NEUROPATHIC PAIN AND
STRESS URINARY INCONTINENCE IN WOMEN (BECAUSE IT INCREASES
URETHRAL TONE).

ATYPICAL ANTIDEPRESSANTS
MIRTAZAPINE

 THIS ANTIDEPRESSANT ACTS BY A NOVEL MECHANISM, VIZ. BLOCKS Α2 AUTO (ON NA NEURONES)
AND HETERO (ON 5HT NEURONES) RECEPTORS ENHANCING BOTH NA AND 5HT RELEASE.
 THE AUGMENTED NA FURTHER INCREASES FIRING OF SEROTONERGIC RAPHE
NEURONES VIA Α1 RECEPTORS.
 SELECTIVE ENHANCEMENT OF ANTIDEPRESSIVE 5HT1 RECEPTOR ACTION IS ACHIEVED BY
CONCURRENT BLOCKADE OF 5HT2 AND 5HT3 RECEPTORS WHICH ARE HELD RESPONSIBLE FOR
SOME OF THE ADVERSE EFFECTS OF HIGH SEROTONERGIC TONE.
 ACCORDINGLY, IT HAS BEEN LABELLED AS “NORADRENERGIC AND SPECIFIC SEROTONERGIC
ANTIDEPRESSANT” (NASSA). IT IS A H1 BLOCKER AND QUITE SEDATIVE, BUT NOT
ANTICHOLINERGIC OR ANTIDOPAMINERGIC.
 EFFICACY IN MILD AS WELL AS SEVERE DEPRESSION IS REPORTED TO BE COMPARABLE TO TCAS
AND BENEFIT MAY START EARLIER.

ATYPICAL ANTIDEPRESSANTS

 BUPROPION


 THIS INHIBITOR OF DA AND NA UPTAKE HAS EXCITANT RATHER THAN SEDATIVE

PROPERTY.
 IT IS METABOLIZED INTO AN AMPHETAMINE LIKE COMPOUND
 IN CLINICAL TRIALS IT HAS BEEN FOUND TO YIELD HIGHER SMOKING ABSTINENCE
AND QUITTING RATES THAN PLACEBO.
 BUPROPION MAY BE ACTING BY AUGMENTING THE DOPAMINERGIC REWARD
FUNCTION.
 THE DOSE OF 150 MG BD SHOULD NOT BE EXCEEDED.



USES OF ANTIDEPRESSANTS

TREATMENT OF ENDOGENOUS (MAJOR) DEPRESSION:

 THE AIM IS TO RELIEVE SYMPTOMS OF DEPRESSION AND RESTORE NORMAL
SOCIAL BEHAVIOUR.
 THE TRICYCLIC AND RELATED ANTIDEPRESSANTS ARE OF PROVEN VALUE.
 RESPONSE TAKES AT LEAST 2–3 WEEKS TO APPEAR, FULL BENEFITS TAKE STILL
LONGER.
 CHOICE OF A PARTICULAR DRUG FOR AN INDIVIDUAL PATIENT DEPENDS ON THE
SECONDARY PROPERTIES (SEDATIVE, ANTICHOLINERGIC, HYPOTENSIVE,
CARDIOTOXIC, SEIZURE PRECIPITATING, ETC.) AS DESCRIBED ABOVE. THE SSRIS
ARE CURRENTLY USED AS FIRST CHOICE FOR THEIR TOLERABILITY AND SAFETY.

 COMBINATION OF A SSRI WITH AN ATYPICAL ANTIPSYCHOTIC (SUCH AS

OLANZAPINE FOR ITS ANTIMANIC PROPERTY) IS ALSO ACCEPTED AS A
TREATMENT OPTION OF BIPOLAR DEPRESSION.

USES OF ANTIDEPRESSANTS

2. OBSESSIVE-COMPULSIVE AND PHOBIC STATES:



 THE SSRIS ARE THE DRUGS OF CHOICE DUE TO BETTER PATIENT

ACCEPTABILITY. TCAS, ESPECIALLY CLOMIPRAMINE, ARE HIGHLY
EFFECTIVE IN OCD AND PANIC DISORDERS: MORE THAN 25%
IMPROVEMENT OCCURS IN OCD RATING SCALE AND PANIC ATTACKS
ARE REDUCED IN >75% PATIENTS. SSRIS AND TCAS ALSO REDUCE
COMPULSIVE EATING IN BULIMIA, AND HELP PATIENTS WITH BODY
DYSMORPHIC DISORDER,
COMPULSIVE BUYING AND KLEPTOMANIA, THOUGH THESE HABITS
MAY NOT COMPLETELY DIE.
USES OF ANTIDEPRESSANTS

 ANXIETY DISORDERS:


 ANTIDEPRESSANTS, ESPECIALLY SSRIS, EXERT A DELAYED BUT

SUSTAINED BENEFICIAL EFFECT IN MANY PATIENTS OF GENERALIZED
ANXIETY DISORDER; MAY BE USED ALONG WITH A SHORT COURSE OF
BZDS TO COVER EXACERBATIONS. SSRIS HAVE ALSO PROVEN
HELPFUL IN POSTTRAUMATIC STRESS DISORDER.

USES OF ANTIDEPRESSANTS

 NEUROPATHIC PAIN:

 IMIPRAMINE AFFORDS CONSIDERABLE RELIEF IN DIABETIC AND SOME

OTHER TYPES OF CHRONIC PAIN. AMITRIPTYLINE REDUCES INTENSITY
OF POSTHERPETIC NEURALGIA IN ~50% PATIENTS.
USES OF ANTIDEPRESSANTS

 ATTENTION DEFICIT-HYPERACTIVITY DISORDER IN CHILDREN:



 TCAS WITH LESS DEPRESSANT PROPERTIES LIKE IMIPRAMINE, NORTRIPTYLINE AND

AMOXAPINE ARE NOW FIRST LINE DRUGS IN THIS DISORDER, COMPARABLE IN
EFFICACY TO AMPHETAMINELIKE DRUGS, WITH THE ADVANTAGE OF LESS FLUCTUATING
ACTION AND FEWER BEHAVIORAL SIDE EFFECTS.

 ENURESIS:


 IN CHILDREN ABOVE 5 YEARS, IMIPRAMINE 25 MG AT BEDTIME IS EFFECTIVE, BUT BED

WETTING MAY AGAIN START WHEN THE DRUG IS STOPPED. ELDERY SUBJECTS WITH
BED WETTING HAVE ALSO BENEFITED.
USES OF ANTIDEPRESSANTS

 MIGRAINE:

 AMITRIPTYLINE HAS SOME PROPHYLACTIC VALUE, ESPECIALLY IN PATIENTS

WITH MIXED HEADACHES.

 PRURITUS:


 SOME TRICYCLICS HAVE ANTIPRURITIC ACTION. TOPICAL DOXEPIN HAS BEEN

USED TO RELIEVE ITCHING IN ATOPIC DERMATITIS, LICHEN SIMPLEX, ETC.

5.SNRIS - ANTIDEPRESSANT.

 THEY WORK BY INCREASING LEVELS OF BOTH SEROTONIN AND

NOREPINEPHRINE IN THE BRAIN.
 NOREPINEPHRINE IS ANOTHER NEUROTRANSMITTER THAT AFFECTS
MOOD. IT WORKS IN A SIMILAR WAY TO SEROTONIN.
 IT IS BELIEVED THAT INCREASED LEVELS OF BOTH SEROTONIN AND
NOREPINEPHRINE CAN HAVE A MORE POSITIVE EFFECT ON MOOD.
RATHER THAN JUST INCREASING LEVELS OF ONE
NEUROTRANSMITTER.
 SOME EXAMPLES OF SNRIS INCLUDE:
 DESVENLAFAXINE (PRISTIQ),
 DULOXETINE (CYMBALTA), AND
 VENLAFAXINE (EFFEXOR).
Conclusion

 To conclude, the types of antidepressants are many and varied, but

all of them work to relieve the symptoms of depression.
 It works by affecting the levels of neurotransmitters in the brain.
 Some types are more effective for certain people than others.
 As the medication options for treating depression continue to grow. It
is important to be informed about the different types of
antidepressants and how they work.