A 42-year-old woman presents with a 3-week history of persistent depressed mood, anhedonia, early morning awakening, and significant psychomotor retardation. She has no prior psychiatric history and no medical comorbidities. What is the drug of choice for her major depressive disorder?

Explanation

## First-Line Antidepressant Selection in MDD **Key Point:** SSRIs (selective serotonin reuptake inhibitors) are the gold-standard first-line agents for major depressive disorder in the absence of specific contraindications or comorbidities. ### Why Sertraline? **High-Yield:** Sertraline is preferred over other SSRIs in this scenario because it: - Has the most robust evidence base in MDD - Demonstrates efficacy across all symptom domains (mood, neurovegetative, cognitive) - Has a favorable side-effect profile with minimal sexual dysfunction compared to other SSRIs - Shows good tolerability in first-episode depression - Is cost-effective and widely available in India ### Comparison of First-Line Agents | Agent | Class | Indication in MDD | Advantage | Disadvantage | | --- | --- | --- | --- | --- | | **Sertraline** | SSRI | First-line | Best efficacy-safety ratio | Sexual dysfunction (less than others) | | Fluoxetine | SSRI | First-line | Long half-life | More sexual dysfunction, drug interactions | | Paroxetine | SSRI | First-line | Anxiolytic effect | High discontinuation syndrome, weight gain | | Escitalopram | SSRI | First-line | High selectivity | Dose-dependent QT prolongation | | Bupropion | NDRI | First-line (special cases) | Activating, no sexual dysfunction | Lowers seizure threshold, anxiety | **Clinical Pearl:** In this patient with psychomotor retardation and early morning awakening (neurovegetative symptoms), an SSRI like sertraline provides balanced restoration of both serotonergic and noradrenergic tone without the activating effects that might overstimulate. ### Dosing and Timeline 1. **Initial dose:** Sertraline 50 mg once daily 2. **Titration:** Increase by 50 mg every 3–7 days as tolerated 3. **Therapeutic range:** 100–200 mg/day 4. **Time to response:** 2–4 weeks (full effect at 6–8 weeks) **Mnemonic:** **SSRI FIRST** — Selective Serotonin Reuptake Inhibitors are First-line In Routine, Standard treatment of depression.