This document discusses various types of antidepressant medications. It describes tricyclic antidepressants (TCAs) such as amitriptyline and selective serotonin reuptake inhibitors (SSRIs) like fluoxetine. Side effects of TCAs include sedation, weight gain, and anticholinergic effects. SSRIs have fewer interactions and side effects than TCAs. Serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine and duloxetine are preferred over TCAs. Monoamine oxidase inhibitors (MAOs) such as moclobemide are reversible and selective, lacking many side effects of other antidepressants. Atypical antidepressants including

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. 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 condition
Types of Depression - Two types
 Unipolar Exogenous / Reactive Depression
 Endogenous/Major Depression (MDD)
 Bipolar

3. Tricyclic Antidepressant (TCA)
AMITRIPTYLINE, NORTRIPTYLINE
IMIPRAMINE, DESIPRAMINE
DOXEPINE, TRIMIPRAMINE
Selective Serotonin Reuptake Inhibitor (SSRI)
SERTRALINE, FLUOXETINE
PAROXETINE, CITALOPRAM, ESCITALOPRAM

4. SNRI-Serotonin and Noradrenaline reuptake
inhibitors
DULOXETINE, VENLAFAXINE
Reversible inhibitors of MAO-A(RIMA)
MOCLOBEMIDE, CLORGYLINE
Atypical Antidepressants
BUPROPION, NEFAZODONE, MIANSERIN,
TRAZODONE, MIRTAZEPINE

5. Depression is due to deficiency of nor-epinephrine &
serotonin
 Normally action of released NE & serotonin is terminated
by active reuptake into the nerve terminal from the
synapse via specific transporters.
 TCAs block the amine transporters (uptake pumps) for
nor-epinephrine (NET) & serotonin (SERT) in brain.
 Facilitation of NE & serotonin transmission ---- improves
symptoms of depression .

6. 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
obsessional
symptoms.
 150mg / day

7. Dothiepin
 Sedative
 Same side effects as
amitryptyline.
 By far and away the
most toxic
antidepressant.
 150 mg / day
Imipramine
 Stimulant
 Anticholinergic ++
 150 mg/ day

8. Antimuscarinic effects
Postural hypotension
Tachycardia, arrhythmias-TCAs potentiate the effect of
directly acting sympathomimetics but inhibit the effect of
indirectly acting sympathomimetics
Sedation
Weight gain
Jittery feeling
Sexual dysfunction (ejaculatory)
Demerits-anticholinergic, cardiovascular and neurological
side effects
Relatively low safety margin, lag time of 2-4wks before
action

9. Anticholinergic drugs aggravative the toxicity of TCAs
T3 and T4 potentiate CNS stimulant effects of TCAs
Phenytoin, chlorpromazine and aspirin displace TCAs
From lprotein binding sites
MOAs and TCAs show synergistic action leading to
serious toxicities
TCAs reverse the antihypertensive effect of alfa2
receptor agonist clonidine

10. Citalopram Few
interactions
Most
expensive
20 mg /day
Fluoxetine Sedation –
Skin S/E
Anxiety +
Cheapest
20-80mg/day
Fluvoxamine Gut S/E + Insomnia - 200 mg /day
Paroxetine Sedation + Withdrawal
problems ?
20 mg /day
Sertraline Diarrhoea 50 mg /day

11.  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 to
titrate dose upwards.

12. MOA: Inhibit Serotonin & NE reuptake at all doses by
binding to NET & SERT
Venlafaxine: Weak Dopamine re-uptake inhibitor at higher
doses. No effect on muscarinic, adrenergic or histaminic
receptors. They are preferred over TCAs for MDD & pain
syndromes
ADR-sweating, anxiety, dizziness, impotence
Duloxetine-used fro panic attacks, diabetic neuropathic pain,
fibromyalgia and stress urinary incontinence in women
ADR-agitation, insomnia and rise in BP

13. MAO –mono amino oxide is a mitochondrial enzyme
involved in oxidative deamination of biological amines
(Adr, NA, DA, 5-HT)
MAO-A inhibitor posses antidepressant acitvity
Moclobemide-Reversible and selective MAO-A inhibitor
Because of competitive enzyme inhibition, tyramine is
able to displace it from the enzyme
It lacks anticholinergic, sedative, cognitive, psychomotar
and cardiovascular side effects
Well tolerated alternative to TCAs
150mg BD max-600mg / day.
ADR- dizziness, insomnia, headache

14. With non-selective MAO inhibitors
cheese wine, pickled meat, fish, yeast extract
Contain large quantities of tyramine, dopa
Indirectly acting sympathomimetics escape
degradation in gut reach systemic circulation and
displace large amount of NA hypertensive crisis,
cerebrovascular accidents
Treatment-phentolamine, chlorpromazine, prazocin

15. MOIs +TCAs- hypertension, arrhythmias and seizures
MOIs inhibit degradation of dopamineNE
hypertension
MOIs are enzyme inhibitors 
MOIs+morphine severe respiratory depression
MOIs+sulfonylureas hypoglycemic coma
MOIs+ chloroquine increased toxicity

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

17. BUPROPION -The inhibitor of DA and NA uptake has
excitant property
Its metabolite is amphetamine like presynaptic
release of DA and NA
Used as an aid for smoking cessation
May be acting by augmenting the dopamine reward
pathway
Adverse effects- insomnia, agitation, dry mouth
C/I- bipolar disorders

18. Mirtazapine : Blocks 5HT2 , & presynaptic α2 receptors.
Enhances release of Serotonin & NE
Amoxapine: Potent Nor-Epinephrine uptake inhibitor but
mild inhibition of Serotonin reuptake. Blocks D2
receptors so has neuroleptic property also
Maprotiline: Potent Nor-Epinephrine uptake inhibitor.

20. All are useful in Major depression, in combination with
other drugs.
Bupropion is useful in ADHD
Bupropion also helps in reducing craving & attenuating
the withdrawal symptoms for Nicotine in tobacco users
trying to quit smoking.
Panic attacks, post traumatic stress disorder
Obsessive compulsive disorder
Nocturnal enuresis
Premenstrual syndrome
Chronic alcoholism