Antidepressants

Dr. Binaya Shrestha

 Introduction
• Depression is characterized by loss of interest
and pleasure, low energy, change in appetite
or sleep.

• Two major types of depression:-

Unipolar depression about 80% of cases
Bipolar depression about 20% of cases
 Hypothesis
• 25% of the unipolar depressed patients are
endogenously depressed and which may occur
at any age and is not self limiting.

• .
• Monoamine hypothesis of endogenous
depression suggests that such depression is
caused by functional deficit of three main
neurotransmitters i.e NE , 5-HT and dopamine
at certain sites in brain while mania results
from functional excess of these
neurotransmitter
 Classification of antidepressant drugs
• Tricyclic antidepressants
Drugs which block both NE and 5-HT reuptake
:- Amitriptyline, Imipramine, Clomipramine
Drugs which mainly blocks NE reuptake:-
Desipramine, Nortriptyline, Amoxapine
• Selective serotonin reuptake inhibitors:-
Sertaline, Paroxetine,Fluoxetine
• Atypical antidepressants:- Trazodone,
Venlafaxine, Bupropion, Mirtazapine
• MAO inhibitors:-
Non selective (both MAO-A and MAO-B
inhibitors):- Tranylcypromine
Selective MAO inhibitors:-Moclobemide
 Tricyclic antidepressants

• Drugs which block both NE and 5-HT reuptake

:- Amitriptyline, Imipramine, Clomipramine
Drugs which mainly blocks NE reuptake:-
Desipramine, Nortriptyline, Amoxapine
 Mechanism of action
• Inhibits reuptake of biogenic amines (5-HT
and/ or NE) into their respective neurons as a
result their concentrations in the synaptic cleft
will be increased and hence their stay at their
receptor site will be prolonged.
 Pharmacokinetics
• Well absorbed orally
• Highly plasma protien bound
• Metabolised in liver
• Excreted in urine
• Fairly long half-life
 Adverse effects
• Anticholinergic effects:- dryness of mouth,
blurred vision, urinary retention, constipation
• Cardiac arrythmias
• Postural hypotension
• Sweating ,tremors
• Increased appetite and weight gain
• Sedation, mental confusion
• Rashes and jaundice
 Drug interactions
• Anticholinergic drugs aggravate the toxicity of
TCAs
• TCAs potentiate the effects of directly acting
sympathomimetics
• TCAs potentiates CNS depressants
• SSRIs inhibits TCAs metabolism increasing
their conc. in plasma
 Therapeutic uses
• Endogenous depression
• Attention deficit Hyperkinetic disorder
• Enuresis and bed wetting in children
• Chronic neuropathic pain
• Migraine
Selective Serotonin reuptake inhibitors
• Currently most commonly prescribed
antidepressant drugs
• SSRIs selectively increases the levels of
serotonin in the synaptic cleft by blocking its
uptake by serotoninergic neurons
 Adverse effects
• Agitation, anxiety and insomnia
• Sexual dysfunction including loss of libido,
delayed ejaculation
• Nausea and loose stools
• Paroxetine causes weight gain
 Therapeutic uses
• Endogenous depression
• Panic disorder
• Obsessive compulsive disorders
• Post traumatic stress disorder
• School phobias
• Eating disorder
 MAO inhibitors
• Increases brain amine levels by inhibiting their
metabolism in their nerve endings,resulting in
an increase in the vesicular stores of NE and 5-
HT
 Adverse effects
• Postural hypotension
• Inappropiate increase in appetite causing
weight gain
• Blurred vision
• Peripheral oedema
• Sexual dysfunction
 Cheese reaction
• An acute attack of hypertension that can occur in a
person taking a monoamine oxidase inhibitor (MAOI)
drug who eats cheese, caused by an interaction of
the MAOI with tyramine, formed in ripe cheese when
bacteria provide an enzyme that reacts with the
amino acid tyrosine in the cheese.