Classification of Antidepressant Drugs

Classification of Antidepressant Drugs | Pharma Info Nepal

Depression is a common mental health disorder characterized by persistent sadness, loss of interest, and a lack of motivation. To treat depression, several classes of antidepressant drugs are used — each working through different mechanisms to restore the balance of neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain.

Classification of Antidepressant Drugs

Antidepressants are broadly classified based on their chemical structure and mechanism of action:

Tricyclic Antidepressants (TCAs)

Examples: Amitriptyline, Imipramine, Nortriptyline, Clomipramine
Mechanism: Inhibit reuptake of serotonin (5-HT) and norepinephrine (NE) at synaptic clefts.
Side effects: Sedation, dry mouth, constipation, blurred vision, cardiac toxicity.
Uses: Major depression, neuropathic pain, migraine prophylaxis.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Examples: Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram
Mechanism: Selectively inhibit reuptake of serotonin, increasing its level in the brain.
Advantages: Fewer side effects compared to TCAs and safer in overdose.
Side effects: Nausea, insomnia, sexual dysfunction.
Uses: Depression, anxiety disorders, OCD, panic disorder.

Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)

Examples: Venlafaxine, Duloxetine, Desvenlafaxine
Mechanism: Block reuptake of both serotonin and norepinephrine.
Uses: Depression, generalized anxiety disorder, neuropathic pain, fibromyalgia.

Monoamine Oxidase Inhibitors (MAOIs)

Examples: Phenelzine, Tranylcypromine, Isocarboxazid
Mechanism: Inhibit MAO enzyme responsible for breakdown of monoamines (5-HT, NE, DA).
Caution: Avoid tyramine-rich foods (e.g., cheese, wine) → risk of hypertensive crisis.
Uses: Atypical depression, resistant depression.

Atypical (or Newer) Antidepressants

These drugs have unique mechanisms and are used when conventional drugs are not effective.

Drug	Mechanism	Remarks
Bupropion	Inhibits dopamine and norepinephrine reuptake	Helps in smoking cessation
Mirtazapine	α2 antagonist → increases NE and 5-HT release	Sedative; increases appetite
Trazodone	Serotonin antagonist and reuptake inhibitor	Causes sedation; used in insomnia
Vilazodone, Vortioxetine	Modulate serotonin receptor activity	Newer generation antidepressants

Serotonin Modulators

Examples: Nefazodone, Trazodone, Vortioxetine
Mechanism: Modulate serotonin receptor and inhibit its reuptake — improving mood with fewer sexual side effects.

Mechanism Summary

Antidepressants act by:

Increasing serotonin, norepinephrine, and/or dopamine levels in the brain.
Enhancing neurotransmission in mood-regulating pathways.
Promoting neuroplasticity and recovery of normal brain function.

Clinical Notes

Antidepressants require 2–4 weeks for full therapeutic effect.
Abrupt withdrawal may cause discontinuation syndrome.
Choice of drug depends on patient symptoms, tolerance, and comorbid conditions.

Understanding the classification and mechanism of antidepressant drugs helps pharmacists and healthcare professionals choose the right therapy for each patient. With proper counseling and monitoring, these medications can greatly improve quality of life for those suffering from depression and related disorders.

Antidepressants: Most Important Exam Points

Prototype SSRI: Fluoxetine.
Prototype TCA: Imipramine.
SSRIs: Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram, Fluvoxamine.
SNRIs: Venlafaxine, Duloxetine.
TCAs: Amitriptyline, Imipramine, Clomipramine, Nortriptyline.
MAO inhibitors: Phenelzine, Tranylcypromine, Isocarboxazid.
Reversible MAO-A inhibitor: Moclobemide.
Long half-life SSRI: Fluoxetine.
Antidepressant used in OCD: Clomipramine.
Antidepressant used for smoking cessation: Bupropion.
Antidepressant historically used for nocturnal enuresis: Imipramine.
Antidepressant associated with priapism: Trazodone.
Antidepressant causing sedation and weight gain: Mirtazapine.
Antidepressant associated with hypertensive crisis after tyramine intake: Phenelzine.
Antidepressant with significant anticholinergic effects: Amitriptyline.
SSRIs inhibit reuptake of: Serotonin (5-HT).
SNRIs inhibit reuptake of: Serotonin and norepinephrine.
TCAs inhibit reuptake of: Serotonin and norepinephrine.
MAOIs inhibit: Monoamine oxidase.
Bupropion inhibits reuptake of: Norepinephrine and dopamine.
Common adverse effect of SSRIs: Sexual dysfunction.
Serious adverse effect of serotonergic antidepressants: Serotonin syndrome.
TCA overdose may cause: Cardiac arrhythmias and QRS widening.
Treatment for significant TCA-induced QRS widening: Intravenous sodium bicarbonate.
Paroxetine: Associated with prominent discontinuation symptoms.
Venlafaxine: Can cause dose-related increases in blood pressure.
Duloxetine: Used for depression and certain types of neuropathic pain.
Sertraline: SSRI commonly used for depression and several anxiety disorders.
Mirtazapine: Blocks presynaptic α₂ receptors and selected serotonin receptors.
Trazodone: Serotonin antagonist and reuptake inhibitor (SARI).
Lithium: Mood stabilizer, not a conventional antidepressant.
Antidepressants usually take: Several weeks to produce substantial clinical improvement.
Abrupt discontinuation of antidepressants: May cause discontinuation symptoms.
SSRIs combined with MAOIs: Can cause potentially life-threatening serotonin syndrome.
TCAs block: Muscarinic, histamine H₁, and α₁ receptors, contributing to adverse effects.