بسم الله الرحمن بسم الله الرحمن بسم الله الرحمن بسم الله الرحمن الرحیمالرحیم

الرحیمالرحیم

Antidepressants

Range

Tricyclics Tetracyclics SSRI SNRI MAOI Oddities Adjuvants

Factors Influencing Choice

Features of illness, e.g. agitation, hypersomia

Suicide risk Other therapy Other illness. Side effects Cost Special problems e.g.

Age, driving, pregnancy

Drug Failure

Non compliance. Inadequate dosage. Other drugs e.g. alcohol, caffeine. Unresolved outside problems. Up to 25% failure even if above

don’t apply.

Tricyclics & Tricyclics & tetracyclics TCAStetracyclics TCAS

Imipramine Imipramine AmitriptylineAmitriptyline Tertiary aminesTertiary amines trimipramintrimipramin TCASTCAS CloimpramineCloimpramine

Secondary Amines DesipramineSecondary Amines Desipramine NortriptylineNortriptyline

Tetracyclic Tetracyclic AmoxpineAmoxpine MaprotilineMaprotiline

PharmacokineticsPharmacokinetics Peak plasma Peak plasma 2-8hr2-8hr Half- lives Half- lives 10-70 10-70 hrhr

P 450 enzyme P 450 enzyme systemsystem

PharmacodynamicsPharmacodynamics Block the reuptake Block the reuptake NENE 5HT5HT Antagonists at:Antagonists at: Muscarinic AchMuscarinic Ach Histamine Histamine H1 H1 alfa alfa 11adrenergicadrenergic alfa alfa 22adrenrgicadrenrgic

Indications Indications

Major depressive disMajor depressive dis Secondary depression Secondary depression Medical Medical

dis dis Movement disMovement dis DementiaDementia

Panic dis ( Imipramine)Panic dis ( Imipramine) Generalized anxiety dis (doxepine)Generalized anxiety dis (doxepine) Obsessive – compulsive dis Obsessive – compulsive dis ClomipramineClomipramine SSRIsSSRIs Eating dis (imipramine,desipramine)Eating dis (imipramine,desipramine) Pain disPain dis EnuresisEnuresis (Imipramine) (Imipramine) Peptic ulcer Peptic ulcer (doxepin) (doxepin) NarcolepsyNarcolepsy

Premature Premature EjaculationEjaculation(( clomipramine)clomipramine)

NightmareNightmare PTSDPTSD ADHDADHD Sleepwalking disSleepwalking dis Separation anxiety disSeparation anxiety dis Sleep terrorSleep terror

Adverse Adverse reactionsreactions

Psychiatric: ManiaPsychiatric: Mania PsychosisPsychosis

Anticholinergics:Anticholinergics:

Dry mouth ( Gum)Dry mouth ( Gum) Constipation (laxative)Constipation (laxative) Blurred visionBlurred vision Urinary retention Urinary retention

(Bethanechol) (Bethanechol) Impotence ( “ ) Impotence ( “ ) Narrow angle glaucoma (mioitc Narrow angle glaucoma (mioitc

agent)agent)

CNS antichcoli:CNS antichcoli: Confusion Confusion

( physostigmine)( physostigmine) deliriumdelirium

SedationSedation serotonergicserotonergic CholinergicCholinergic HistaminergicHistaminergic

Autonomic effectsAutonomic effects Orthostatic hypotensionOrthostatic hypotension

(fludrocortisone 0—05mg (fludrocortisone 0—05mg X2)X2)

SweatingSweating PalpitationsPalpitations Blood pressure Blood pressure

CardiacCardiac effects effects Tachycardia Tachycardia Flattened T wavesFlattened T waves Prolonged QTProlonged QT S.T S.T Quinidinelike effect Quinidinelike effect

PVCPVC

At high plasma concentrations At high plasma concentrations arrhythmogenicarrhythmogenic Hypertensive episodes during Hypertensive episodes during

surgerysurgery

Neurological effectsNeurological effects SedationSedation Delirium Delirium Psychomotor stimulationPsychomotor stimulation Myoclonic twitchesMyoclonic twitches Speech blockage Speech blockage ParesthesiaParesthesia Peroneal palsiesPeroneal palsies AtaxiaAtaxia Seizure ( maprotiline)Seizure ( maprotiline) Lower the seizure threshold (Clomipramine – Lower the seizure threshold (Clomipramine –

Amoxapin) Amoxapin)

Allergic effectsAllergic effects

Exanthematous 4-5%Exanthematous 4-5%((marprotilinemarprotiline) )

JaundiceJaundice

Hematological effects Hematological effects AgranulocytosisAgranulocytosis

LeukocytosisLeukocytosis LeukopeniaLeukopenia EosinophiliaEosinophilia

Sore throat Sore throat CBCCBC

Other adverse effectsOther adverse effects Weight gainWeight gain ImpotenceImpotence GynecomastiaGynecomastia AmenorrheaAmenorrhea SIADHSIADH HepatitisHepatitis

Drug – Drug Drug – Drug InteractionsInteractions

TCAS Block: TCAS Block: propranololpropranolol ClonidineClonidine GuanethidineGuanethidine

TCAS increas : Antipsychotics TCAS increas : Antipsychotics levellevel

TCAS+ sympathomimetics TCAS+ sympathomimetics serious serious CardiovascularCardiovascular effectseffects

Oral contraceptives TCAOral contraceptives TCA

AcetazolamideAcetazolamide AspirinAspirin Cimetidine TCACimetidine TCA ThiazideThiazide FluoxetineFluoxetine Sodium bicarbonateSodium bicarbonate

Ascorbic acidAscorbic acid Ammonium chloridAmmonium chlorid BarbituratesBarbiturates Cigarette smoking TCACigarette smoking TCA Chloral hydrateChloral hydrate LithiumLithium PrimidonePrimidone

TCAS additive effects:TCAS additive effects: Opioids Opioids AlcoholAlcohol AnxiolyticsAnxiolytics HypnoticsHypnotics Over – the – counter Over – the – counter

coldcold

GuidelinesGuidelines CBCCBC LFTLFT ElectrolytesElectrolytes ECGECG

DosageDosage TCAS: 150-300 mgTCAS: 150-300 mg Nortriptyl : 50-150 Nortriptyl : 50-150

mgmg

Overdose Overdose AttemptsAttempts

AgitationAgitation DeliriumDelirium ConvulsionsConvulsions Hyperactive deep tendon reflex'sHyperactive deep tendon reflex's Bowel and bladder paralysisBowel and bladder paralysis Dysregulation of (BP) and temperatureDysregulation of (BP) and temperature Mydriasis Mydriasis Coma Coma Respiratory depression Respiratory depression Cardiac arrhythmias (3-4days)Cardiac arrhythmias (3-4days)

Treatment – resistant Treatment – resistant DepressionDepression

Lithium ( 900-1200 mg)Lithium ( 900-1200 mg) Liothyronine( T3 ) ( 25-50 mg)Liothyronine( T3 ) ( 25-50 mg) T4T4

Selective Serotonin reuptake Inhibitors

SSRIs

SSRIs Fluoxetine Fluvoxamine Paroxetine Sertraline Citalopram Escitalopram

Indication Depression Sertraline Fluoxetine Obsessive – Compulsive Disorder (OCD) Floxentine Panic dis citalopram Eating dis Bulimia Fluoxetine Anorexia Fluoxetine B.P.D Social phobia Paroxetine PTSD PMS Premataure Ejaculation Fluoxtine Sertraline

Sexual obsessions ADHD Autistic dis Fluoxetine Neuropathic pain Fibromyalgia Headache Psychosomatic conditions Fluoxetine Syncope sertraline CopD sertraline

Pharmacokinetics

half life = 1-3 daysmetabolized : liverP4 5O – Cyp 2D6

Pharmacodynamics Inhibition of serotonin Reuptake

Augmentation Strategies

Pregnancy

Fluoxetine IQ Language delays Behavioral problems Neonatal Jitteriness Tachypnea

Depression in Mechicallyill

Dression in Mechicallyill

Treatment of Depression

Excessive Physical morbidity

Myocardial InfarctionProlonged hospitalization Death

Depression in Medically ill

Fluoxetine 20-80 mgSertraline 50-200 mgParoxetine 40-60 mgCitalopram 20-60 mgFluvoxamine 50-300 mg

Adverse Reactions

¾ no side effects 10-15% no tolerate

Sexual dysfunction Inhibited orgasm Decreased libido Bupropion Yohimbine Cyproheptadine Bromocriptine Amantadine Sildenafil Amphetamine(5mg)

Gastrointestinal adverse effects

Nausea Diarrhea Anorexia Vomiting Dyspepsia

Weight gain Paroxetine

Headaches 18-20% Fluoxetine

AnxietyFluoxetine

Insomnia Fluoxetine Benzodiazepines

Trazodone

–Sedation Citalopram

– Paroxetine

– Bupropion

Vivid Dreams

Seizures

– 0.1 - 0.2% Fluoxetine >100mg

Extrapyramidal symptoms

Tremor 5-10%– Akathisia

Dystonia Cogwheel rigidity Torticollis Opisthotonos Gait dis Bradykinesia Tardive Dyskinesia Bruxism (Buspirone)

Anticholinergic effects Paroxetine Dry mouth Constipation

Sedation

Hematological adverse effects Paroxetine Fluoxetine Increase Bruisability

Neutropenia

Electrolyte Glucose concentration Hyponatremia Secretion of inappropriate antidiuretic

Hormone ( SIADH)

Endocrine Prolactin

mammoplasia

Galactorrhea

Allergic reactions

Rashes Pulmonary system(fibrotic) Dyspnea

Serotonin syndrome

MAOIS L-tryptophan Lithium

Diarrhea Restlessness Extreme agitation Hyperreflexia Autonomic instability

Myoclonus Seizures Hyperthermia Shivering Rigidity Delirium Coma Status epilepticus Cardiovascular collaps Death

Supportive careNitrvoglycerineCyproheptadineMethysergideCooling blanketsChlorpromazineDantrolene BenzodiazepinesArticonvulsants Mechanical ventilationParalyzing agents

SSRI Withdrawal

DizzinessWeaknessNauseaHeadache AnxietyInsomniaPoor concentrationUpper respiratory symptoms ParesthesiaMigrain like symptome

Drug – Drug interactions

Fluoxetine Carbamazepine

Antineoplastic A.

Diazepam

Phenytoin

Warfarin

Sertraline PT

Paroxetine

PTCPP 2D6

Antidepressants PhenothiazinesAntiarrhythmic d.

Fluvoxamine

Most Risk for interactions

venlafexine, Effexor® 1st available as IR, not well tolerated Approval of XR resulted in better

tolerance at higher doses better efficacy Available in 37.5-75-150mg caps Dose range 75-300 in XR form Half life 5 hours steady state in 3 days,

longer with XR preparation Very effective with comorbid depression

and anxiety , OCD, panic

Anti-anxiety effect present at higher doses >150mg QD

No weight gain Rare sedation Dizziness, lightheaded, restless,

disturbed sleep more common Sweating, headaches Side effects are usually transient at onset

of treatment

Duloxitine, Cymbalta® Newest addition to SSRI/SNRI group Available 30-40-60mg caps Dose range 30-120mg QD Marketed as effective for patients with

somatic/pain issues More efficacious SNRI mg for mg than

venlafexine

Very useful in the elderly with chronic pain, discomfort

Effective with FMS As effective as venlafexine in anxiety,

panic Not as efficacious as venlafexine in OCD,

by experience Well tolerated, no sedation, weight gain Dry mouth, headaches, restless, insomnia

dose related

buproprion, Wellbutrin SR, XL® SNRI & dopamine reuptake inhibitor Available 100-150-200SR, 75-100-150IR,

100-150-300XL, tabs Dosage range 75-450mg QD rarely

exceeds 300mg QD Half life 20 hours, steady state 2-4 weeks Effective for depression with low mood ,

energy and motivation, (anhedonia)

Effective at addressing cognitive symptoms associated with mood disorders.

Improves attention and concentration and mental energy.

Well tolerated no sedation, weight gain, no sexual dysfunction

Headaches, restless, rare agitation, insomnia

Venlafaxine Selective Serotonin and

noradrenaline reuptake inhibitor – like amitryptyline.

Few other effects – unlike amitryptyline.

75-150mg / day minimum Dry mouth, somnolence, high BP,

nausea, headache and dizziness.

The old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete.

Moclobemide. Only MAOI-A. ? Role. ? Special place in anxiety

disorder. 300-600mg / day.

Trazodone. Unique structure. Low cardiotoxicity, few

anticholinergic side effects. Drowsiness +. Nausea. 150 mg /day.