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ANTI DEPRESSANT ANTI DEPRESSANT DRUGSDRUGS

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DEPRESSIONDEPRESSION INTENSE FEELINGS OF SADNESSINTENSE FEELINGS OF SADNESS HOPELESSNESSHOPELESSNESS DESPAIRDESPAIR INABILITY TO EXPERIENCE INABILITY TO EXPERIENCE

PLEASURE IN USUAL ACTIVITIES..PLEASURE IN USUAL ACTIVITIES.. Weight loss/weight gainWeight loss/weight gain Changes in sleep patternChanges in sleep pattern Recurrent thoughts of deathRecurrent thoughts of death Suicidal tendenciesSuicidal tendencies

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MANIAMANIA OPPOSITE BEHAVIOROPPOSITE BEHAVIOR ENTHUSIASMENTHUSIASM RAPID THOUGHT AND SPEECH .RAPID THOUGHT AND SPEECH . IMPAIRED JUDGEMENT.IMPAIRED JUDGEMENT.

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Causes of depressionCauses of depression

Heredity – upto 40%Heredity – upto 40% Psychological-low self esteemPsychological-low self esteem Life experiences-poverty, Life experiences-poverty,

unemployment, death of parent unemployment, death of parent Medical conditions- hepatitis, Medical conditions- hepatitis,

hypothyroidism, parkinsonshypothyroidism, parkinsons In women –ante/post natal, post In women –ante/post natal, post

menopausal menopausal

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Antidepressant DrugsAntidepressant Drugs

BLOCKADE OF BLOCKADE OF NEUROTRANSMITTER REUPTAKENEUROTRANSMITTER REUPTAKE

DOPAMINEDOPAMINE SEROTONINSEROTONIN NOREPINEPHRINENOREPINEPHRINE

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Tricyclic antidepressants Tricyclic antidepressants (TCAs)(TCAs)

Amitriptyline Amitriptyline Imipramine - NOREPINEPHRINEImipramine - NOREPINEPHRINE DesipramineDesipramine Doxepin Doxepin Clomipramine - SEROTONINClomipramine - SEROTONIN Nortriptyline Nortriptyline ProtriptylineProtriptyline Maprotiline – Second generationMaprotiline – Second generation Amoxapine -- Second generationAmoxapine -- Second generation

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MODE OF ACTIONMODE OF ACTION

INHIBITION OF NUEROTRANSMITTER INHIBITION OF NUEROTRANSMITTER REUPTAKEREUPTAKE

BLOCKING OF RECEPTORS BLOCKING OF RECEPTORS (Serotonergic, adrenergic, histamine, (Serotonergic, adrenergic, histamine, muscarinic)muscarinic)

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Actions Actions

Elevate moodElevate mood Improve mental alertnessImprove mental alertness ↑ ↑ physical activityphysical activity More than 2 weeks need..More than 2 weeks need..

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Tricyclic AntidepressantsTricyclic Antidepressants

Most Common Adverse EffectsMost Common Adverse Effects Urinary retention Urinary retention Constipation Constipation Weight Gain Weight Gain Sexual Dysfunction Sexual Dysfunction Confusion/Delirium Confusion/Delirium Orthostatic Hypotension Orthostatic Hypotension

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Drug-Drug InteractionsDrug-Drug Interactions

MAO Inhibitors: MAO Inhibitors: Hypertensive Crisis, Tachycardia, Hypertensive Crisis, Tachycardia,

Seizures Seizures

  Antihypertensive Medications:Antihypertensive Medications: Potentiation of Orthostatic Hypotension, Potentiation of Orthostatic Hypotension,

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Drug-Drug InteractionsDrug-Drug Interactions

Sympathomimetics:Sympathomimetics: Increased Cardiotoxicity, Increased Cardiotoxicity,

Cimetidine :Cimetidine : Decreased liver metabolism Decreased liver metabolism

resulting in higher Imipramine levels resulting in higher Imipramine levels

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Over dosage Over dosage

restlessness/excitement restlessness/excitement

tonic-clonic seizures or dystonia tonic-clonic seizures or dystonia

Hypoxia, hypotensionHypoxia, hypotension

coma coma

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AmitriptylineAmitriptyline anticholinergic properties greater anticholinergic properties greater

than Imipramine than Imipramine

sedation: > Imipramine sedation: > Imipramine

antihistaminic properties antihistaminic properties

orthostatic hypotension ???orthostatic hypotension ???

mild analgesic mild analgesic

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Clinical usesClinical uses

endogenous depression endogenous depression prophylaxis for migraine  prophylaxis for migraine  eating disorder associated with eating disorder associated with

depression  depression  sedative for non-depressed patients sedative for non-depressed patients

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ImipramineImipramine - Clinical uses - Clinical uses

  endogenous depression endogenous depression   reactive depression reactive depression   enuresis enuresis alcoholism  alcoholism  cocaine withdrawal  cocaine withdrawal  attention deficit disorders  attention deficit disorders  with amphetamine or with amphetamine or

methyphenidate for narcolepsy  methyphenidate for narcolepsy 

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ClomipramineClomipramine - Clinical Uses: - Clinical Uses:

Obsessive-compulsive disorder Obsessive-compulsive disorder panic disorderpanic disorder agoraphobia agoraphobia

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Monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAO-I’s)(MAO-I’s)

Phenelzine Phenelzine

Tranylcypromine Tranylcypromine

Clorgyline (specific for MAO type A )Clorgyline (specific for MAO type A )

Isocarboxazid Isocarboxazid

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Clinical UsesClinical Uses

endogenous depression endogenous depression

depressive phase of bipolar disorder depressive phase of bipolar disorder

severe reactive depression not severe reactive depression not responsive to other drugsresponsive to other drugs

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Most Common Adverse EffectsMost Common Adverse Effects Sleep disturbances Sleep disturbances Orthostatic Hypotension Orthostatic Hypotension Weight Gain Weight Gain Sexual Dysfunction Sexual Dysfunction Drug/Food Interactions **Drug/Food Interactions ** Food – Tyramine (cheese, chicken Food – Tyramine (cheese, chicken

liver, beer, red wine)liver, beer, red wine)

With SSRIS : SEROTONIN SYNDROME.With SSRIS : SEROTONIN SYNDROME. TOXICITY : SUPPORTIVE THERAPYTOXICITY : SUPPORTIVE THERAPY

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Drug-Drug Interactions Drug-Drug Interactions

TCASTCAS SSRISSSRIS BUSPIRONEBUSPIRONE SYMPATHOMIMETICSSYMPATHOMIMETICS CNS DEPRESSANTSCNS DEPRESSANTS OPIOD ANALGESICSOPIOD ANALGESICS GENERAL ANAESTHESIAGENERAL ANAESTHESIA

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Selective Serotonin - Reuptake Selective Serotonin - Reuptake Inhibitors - (SSRIs)Inhibitors - (SSRIs)

Fluoxetine Fluoxetine Sertraline Sertraline Paroxetine Paroxetine Nefazodone Nefazodone Trazodone Trazodone

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ActionAction

New groupNew group Selectively inhibit serotonin Selectively inhibit serotonin

reuptake.reuptake. Fewer anticholinergic and lower Fewer anticholinergic and lower

cardiac toxicity.cardiac toxicity.

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Clinical Uses:Clinical Uses:

endogenous depression endogenous depression obsessive-compulsive disorder obsessive-compulsive disorder obesity obesity bulimia nervosa – (Fluoxetine) bulimia nervosa – (Fluoxetine)

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Most Common Adverse Effects:Most Common Adverse Effects:

Nausea Nausea Headache Headache Insomnia Insomnia Nervousness Nervousness Fatigue Fatigue Sexual DysfunctionSexual Dysfunction Inappropriate ADH secretion Inappropriate ADH secretion Extrapyramidal effects Extrapyramidal effects

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Drug-Drug Interactions Drug-Drug Interactions

Tryptophan Tryptophan

TCASTCAS

MAO – I ‘sMAO – I ‘s

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Lithium PharmacologyLithium Pharmacology

Absorption : oralAbsorption : oral Excretion : urineExcretion : urine Very toxicVery toxic

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Mech ????Mech ????

Neurotransmitter release modulationNeurotransmitter release modulation Li – Na exchangeLi – Na exchange

Second messenger effectSecond messenger effect PIP2 (Phoshphadityl Inositol PIP2 (Phoshphadityl Inositol

biphosphate) biphosphate) ↓↓

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RxRx

Manic depressive patientsManic depressive patients Acute manic episodesAcute manic episodes Prevent recurrence of maniaPrevent recurrence of mania

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Adverse Effects Adverse Effects

Tremor-- common side effect Tremor-- common side effect choreoathetosis choreoathetosis motor hyperactivity motor hyperactivity ataxia ataxia dysarthria dysarthria aphasia aphasia Psychiatric manifestations Psychiatric manifestations

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OthersOthers

Thyroid function effects Thyroid function effects Renal Effects: Renal Effects: Polydipsia; polyuria Polydipsia; polyuria Edema Edema Cardiac Effects - arrhythmias Cardiac Effects - arrhythmias Contraindicated in pregnancy Contraindicated in pregnancy

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Lithium OverdosageLithium Overdosage

peritoneal dialysis -- effective peritoneal dialysis -- effective hemodialysis -- effective; preferred hemodialysis -- effective; preferred

Other mood stabilizers: Other mood stabilizers: Carbamazepine Carbamazepine Valproic acidValproic acid

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PSYCHIATRIC COUNSELLINGPSYCHIATRIC COUNSELLING MEDITATION ( yoga)MEDITATION ( yoga)

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Don’t worry Don’t worry be be

Happy Happy