Antidepressants are highly effective for depression, anxiety, and obsessive–compulsive symptoms—but no medication works in a vacuum. Each class of antidepressant influences the brain’s chemistry in slightly different ways, producing predictable patterns of side effects. Most are mild and temporary, but knowing how to anticipate and manage them can make treatment smoother and safer.

1. SSRIs (Selective Serotonin Reuptake Inhibitors)

Examples: Fluoxetine, Sertraline, Escitalopram, Paroxetine, Citalopram

Common Side Effects

• Nausea, diarrhea, or indigestion: due to increased serotonin activity in the gut.
• Headache, restlessness, or sleep disturbance: especially early in treatment.
• Sexual dysfunction: decreased libido, delayed orgasm, or genital numbness.
• Initial anxiety or jitteriness: sometimes seen in panic or anxious depression.

Management

• Take the medication after meals and maintain hydration.
• Start low and go slow—dose escalation should be gradual.
• Use night-time dosing if the drug causes drowsiness (e.g., paroxetine) or morning dosing if activating (e.g., fluoxetine).
• If sexual dysfunction persists, options include dose reduction, drug holidays (only under supervision), or switching to bupropion or mirtazapine.
• Short-term benzodiazepines may be used early for severe activation.

2. SNRIs (Serotonin–Norepinephrine Reuptake Inhibitors)

Examples: Venlafaxine, Desvenlafaxine, Duloxetine, Levomilnacipran

Common Side Effects

• Dry mouth, sweating, or constipation due to noradrenergic activity.
• Increased blood pressure or heart rate (especially at higher doses).
• Nausea, dizziness, insomnia, or tremor.

Management

• Monitor blood pressure regularly, particularly with venlafaxine.
• Avoid caffeine and ensure good hydration.
• If anxiety increases, lower the dose and titrate slowly.
• Take duloxetine or venlafaxine with food to reduce nausea.
• For persistent insomnia, schedule doses in the morning and use relaxation or melatonin-based sleep aids.

3. Atypical Antidepressants

a. Bupropion

(Dopamine–Norepinephrine Reuptake Inhibitor)
Side Effects: Insomnia, dry mouth, tremor, weight loss, and anxiety.
Tips:

• Best for patients with fatigue or sexual side effects from SSRIs.
• Avoid in those with seizure disorders or heavy alcohol use.
• Morning dosing minimizes insomnia.

b. Mirtazapine

(Noradrenergic and Specific Serotonergic Antidepressant)
Side Effects: Sedation, weight gain, increased appetite.
Tips:

• Excellent choice for depressed patients with insomnia or weight loss.
• Taking it at bedtime enhances sleep and reduces daytime drowsiness.

c. Agomelatine (where available)

(Melatonergic agonist and 5-HT₂C antagonist)
Side Effects: Mild nausea, dizziness, elevated liver enzymes.
Tips:

• Periodic liver function tests are essential.
• Improves sleep-wake rhythm with minimal sexual effects.

4. Tricyclic Antidepressants (TCAs)

Examples: Amitriptyline, Nortriptyline, Imipramine, Dothiepin

Common Side Effects

• Dry mouth, constipation, blurred vision, urinary retention (anticholinergic).
• Weight gain and drowsiness due to histaminergic blockade.
• Cardiac conduction changes at higher doses.

Management

• Encourage hydration, fiber, and sugar-free lozenges for dryness.
• Take at night to use sedation therapeutically.
• In older adults, prefer nortriptyline or desipramine (less anticholinergic).
• Obtain ECG before use in cardiac patients.

5. MAOIs (Monoamine Oxidase Inhibitors)

Examples: Phenelzine, Tranylcypromine, Moclobemide

Common Side Effects

• Weight gain, orthostatic hypotension, insomnia, sexual dysfunction.
• Risk of hypertensive crisis with tyramine-rich foods (aged cheese, cured meats, wine).

Management

• Educate patients thoroughly about dietary restrictions.
• Moclobemide (a reversible MAOI) is safer with fewer food interactions.
• Monitor blood pressure closely during initiation and dose changes.

6. Newer and Add-on Agents

Vortioxetine

• Improves cognition and has fewer sexual side effects.
• Common effects: nausea, mild headache—usually transient.

Esketamine (intranasal)

• Transient dizziness or dissociation; always administered under medical supervision.

Tianeptine

• Minimal sexual dysfunction, rare GI discomfort.

7. General Principles of Managing Side Effects

1. Educate before prescribing: patients who expect side effects tolerate them better.
2. Start low, titrate slow: abrupt dosage jumps increase dropouts.
3. Monitor at 2 and 6 weeks: most early adverse effects fade by then.
4. Rule out medical causes: hypothyroidism, diabetes, and vitamin deficiencies can mimic or worsen side effects.
5. Collaborate and personalize: what feels intolerable for one patient may be manageable for another—treatment must fit the person, not just the diagnosis.

8. When to Seek Immediate Medical Attention

Certain side effects require urgent review:

• Persistent vomiting or diarrhea causing dehydration
• Confusion, agitation, or muscle rigidity (possible serotonin syndrome)
• Severe rash or swelling
• Palpitations or fainting spells

9. The Takeaway

Every antidepressant carries trade-offs, but almost all side effects are manageable with the right strategy. Open communication between patient and psychiatrist prevents premature discontinuation and ensures sustained recovery.

The best antidepressant is not the one with no side effects—but the one you can live with comfortably while getting well.

Author:
Dr. Srinivas Rajkumar T, MD (AIIMS Delhi), DNB, MBA (BITS Pilani)
Consultant Psychiatrist, Mind & Memory Clinic
Apollo Clinic Velachery (opposite Phoenix MarketCity), Chennai
📞 +91 85951 55808 | 🌐 srinivasaiims.com