Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSORDEPT. OF PHARMACOLOGYSSIMS & RC.

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They are among the most commonly prescribed drugs .Depression: It is a the most commonly serious disorder of

mood, ranges from mild to very serious conditionTypes of Depression - Two types Unipolar Exogenous / Reactive Depression Endogenous/Major Depression (MDD) Bipolar

Tricyclic Antidepressant (TCA)AMITRIPTYLINE, NORTRIPTYLINEIMIPRAMINE, DESIPRAMINEDOXEPINE, TRIMIPRAMINE

Selective Serotonin Reuptake Inhibitor (SSRI)SERTRALINE, FLUOXETINEPAROXETINE, CITALOPRAM, ESCITALOPRAM

SNRI-Serotonin and Noradrenaline reuptakeinhibitorsDULOXETINE, VENLAFAXINEReversible inhibitors of MAO-A(RIMA)MOCLOBEMIDE, CLORGYLINEAtypical AntidepressantsBUPROPION, NEFAZODONE, MIANSERIN,TRAZODONE, MIRTAZEPINE

Depression is due to deficiency of nor-epinephrine &serotonin

Normally action of released NE & serotonin is terminatedby active reuptake into the nerve terminal from thesynapse via specific transporters.

TCAs block the amine transporters (uptake pumps) fornor-epinephrine (NET) & serotonin (SERT) in brain.

Facilitation of NE & serotonin transmission ---- improvessymptoms of depression .

Amitryptyline Potent sedative Weight gain ++ Anticholinergic ++ Most researched 150mg / day(Therapeutic in 95% of

adults)

Clomipramine Similar side effects to

amitryptyline. Said to be best for

obsessionalsymptoms.

150mg / day

Dothiepin Sedative Same side effects as

amitryptyline. By far and away the

most toxicantidepressant.

150 mg / day

Imipramine Stimulant Anticholinergic ++ 150 mg/ day

Antimuscarinic effectsPostural hypotensionTachycardia, arrhythmias-TCAs potentiate the effect ofdirectly acting sympathomimetics but inhibit the effect ofindirectly acting sympathomimetics

SedationWeight gainJittery feelingSexual dysfunction (ejaculatory)Demerits-anticholinergic, cardiovascular and neurologicalside effectsRelatively low safety margin, lag time of 2-4wks beforeaction

Anticholinergic drugs aggravative the toxicity of TCAsT3 and T4 potentiate CNS stimulant effects of TCAsPhenytoin, chlorpromazine and aspirin displace TCAsFrom lprotein binding sitesMOAs and TCAs show synergistic action leading toserious toxicitiesTCAs reverse the antihypertensive effect of alfa2receptor agonist clonidine

Citalopram Fewinteractions

Mostexpensive

20 mg /day

Fluoxetine Sedation –Skin S/E

Anxiety +Cheapest

20-80mg/day

Fluvoxamine Gut S/E + Insomnia - 200 mg /day

Paroxetine Sedation + Withdrawalproblems ?

20 mg /day

Sertraline Diarrhoea 50 mg /day

First choice in elderly. First choice if heart

disease. First choice if suicide

risk. More expensive.

Side effects Like TCA reduce with

time. Gut problems

predominate. Flat dose response

curve – so no need totitrate dose upwards.

MOA: Inhibit Serotonin & NE reuptake at all doses by

binding to NET & SERTVenlafaxine: Weak Dopamine re-uptake inhibitor at higher

doses. No effect on muscarinic, adrenergic or histaminicreceptors. They are preferred over TCAs for MDD & painsyndromes

ADR-sweating, anxiety, dizziness, impotenceDuloxetine-used fro panic attacks, diabetic neuropathic pain,

fibromyalgia and stress urinary incontinence in womenADR-agitation, insomnia and rise in BP

MAO –mono amino oxide is a mitochondrial enzymeinvolved in oxidative deamination of biological amines(Adr, NA, DA, 5-HT)MAO-A inhibitor posses antidepressant acitvityMoclobemide-Reversible and selective MAO-A inhibitorBecause of competitive enzyme inhibition, tyramine isable to displace it from the enzymeIt lacks anticholinergic, sedative, cognitive, psychomotarand cardiovascular side effectsWell tolerated alternative to TCAs150mg BD max-600mg / day.ADR- dizziness, insomnia, headache

With non-selective MAO inhibitorscheese wine, pickled meat, fish, yeast extractContain large quantities of tyramine, dopaIndirectly acting sympathomimetics escapedegradation in gut reach systemic circulation anddisplace large amount of NA hypertensive crisis,cerebrovascular accidentsTreatment-phentolamine, chlorpromazine, prazocin

MOIs +TCAs- hypertension, arrhythmias and seizuresMOIs inhibit degradation of dopamineNEhypertensionMOIs are enzyme inhibitorsMOIs+morphine severe respiratory depressionMOIs+sulfonylureas hypoglycemic comaMOIs+ chloroquine increased toxicity

Trazodone-first atypical antidepressant, blocks5-HT uptake and has prominent α adrenergic andweak 5HT2 antagonistic propertyBeneficial to OCD (Obsessive Compulsive Disorder)Low cardiotoxicity, few anticholinergic side effects.Drowsiness, Nausea.150 mg /day.

BUPROPION -The inhibitor of DA and NA uptake hasexcitant propertyIts metabolite is amphetamine like presynapticrelease of DA and NAUsed as an aid for smoking cessationMay be acting by augmenting the dopamine rewardpathwayAdverse effects- insomnia, agitation, dry mouthC/I- bipolar disorders

Mirtazapine : Blocks 5HT2 , & presynaptic α2 receptors.Enhances release of Serotonin & NEAmoxapine: Potent Nor-Epinephrine uptake inhibitor but

mild inhibition of Serotonin reuptake. Blocks D2receptors so has neuroleptic property also

Maprotiline: Potent Nor-Epinephrine uptake inhibitor.

All are useful in Major depression, in combination withother drugs.Bupropion is useful in ADHD

Bupropion also helps in reducing craving & attenuatingthe withdrawal symptoms for Nicotine in tobacco userstrying to quit smoking.Panic attacks, post traumatic stress disorderObsessive compulsive disorderNocturnal enuresisPremenstrual syndromeChronic alcoholism