A 38-year-old woman presents with a 3-week history of persistent depressed mood, anhedonia, sleep disturbance, and feelings of worthlessness. She has no significant past psychiatric history and no contraindications to antidepressants. Which is the drug of choice for first-line treatment of her major depressive disorder?

Question

Accepted Answer

D. Sertraline. ## First-Line Antidepressants in Major Depressive Disorder

**Key Point:** Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for major depressive disorder in the absence of specific contraindications or clinical factors favouring an alternative agent.

### Why SSRIs Are First-Line

1. **Efficacy**: Comparable to tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) in treating depression.
2. **Safety profile**: Significantly better tolerability and lower toxicity in overdose.
3. **Side effect burden**: Fewer anticholinergic effects, weight gain, and cardiac conduction abnormalities compared to TCAs.
4. **Drug interactions**: Fewer interactions than MAOIs; safer in combination therapies.

### Common First-Line SSRIs

| SSRI | Typical Dose (mg/day) | Half-life | Key Feature |
|------|----------------------|-----------|-------------|
| Sertraline | 50–200 | 26 hours | Fewer drug interactions; good GI tolerability |
| Escitalopram | 10–20 | 27–32 hours | Most selective; minimal interactions |
| Citalopram | 20–40 | 35 hours | Caution: QTc prolongation at high doses |
| Fluoxetine | 20–80 | 4–6 days | Long half-life; useful in non-adherence |
| Paroxetine | 20–50 | 21 hours | Anticholinergic effects; weight gain risk |

**High-Yield:** Sertraline is often preferred in India due to cost, availability, and robust evidence base in clinical practice.

### Clinical Pearl

**Tip:** In this case—a patient with no past psychiatric history, no contraindications, and uncomplicated depression—an SSRI is the standard of care. Response typically occurs within 2–4 weeks; full effect may take 8–12 weeks.

## Why Other Options Are Not First-Line

- **Amitriptyline (TCA)**: Second-line due to anticholinergic side effects, orthostatic hypotension, cardiac conduction risks, and lethality in overdose. Reserved for patients with concurrent neuropathic pain or insomnia requiring sedation.
- **Phenelzine (MAOI)**: Third-line; requires dietary restrictions (tyramine avoidance), dangerous drug interactions, and hypertensive crisis risk. Used only after SSRIs and SNRIs have failed.
- **Lithium**: Not an antidepressant monotherapy; used as an augmentation agent in treatment-resistant depression or as mood stabilizer in bipolar disorder. Requires therapeutic drug monitoring and careful renal/thyroid assessment.

[cite:Harrison 21e Ch 470]

Answer

A. Amitriptyline

Answer

B. Phenelzine

Answer

C. Lithium

Explanation

First-Line Antidepressants in Major Depressive Disorder

Why SSRIs Are First-Line

Common First-Line SSRIs

Clinical Pearl

Why Other Options Are Not First-Line

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SSRI	Typical Dose (mg/day)	Half-life	Key Feature
Sertraline	50–200	26 hours	Fewer drug interactions; good GI tolerability
Escitalopram	10–20	27–32 hours	Most selective; minimal interactions
Citalopram	20–40	35 hours	Caution: QTc prolongation at high doses
Fluoxetine	20–80	4–6 days	Long half-life; useful in non-adherence
Paroxetine	20–50	21 hours	Anticholinergic effects; weight gain risk