A 38-year-old woman presents to the psychiatry outpatient clinic with a 4-month history of persistent low mood, anhedonia, and significant functional impairment. She reports waking up at 4 AM every morning and being unable to return to sleep. Her appetite has decreased markedly, and she has lost 8 kg unintentionally. She expresses feelings of worthlessness and guilt over minor past events. On mental status examination, her speech is slow and her affect is blunted. She denies any suicidal ideation currently but admits to passive death wishes. Physical examination and routine blood work including TSH are normal. What is the most appropriate first-line pharmacological intervention?

Explanation

## Diagnosis and Treatment Rationale This patient presents with a clear case of **Major Depressive Disorder (MDD)** with melancholic features, evidenced by: - Persistent depressed mood for >2 weeks (4 months here) - Anhedonia (loss of pleasure) - Early morning awakening (terminal insomnia) - Significant appetite loss and weight loss - Psychomotor retardation (slow speech) - Feelings of guilt and worthlessness - Functional impairment ### First-Line Pharmacotherapy **Key Point:** SSRIs (Selective Serotonin Reuptake Inhibitors) are the gold-standard first-line agents for MDD in both depression with and without melancholic features. **High-Yield:** Fluoxetine 20 mg once daily is a classic SSRI choice for MDD. It has: - Good efficacy across depressive subtypes - Favorable side-effect profile - Once-daily dosing (improves adherence) - Extensive evidence base in Indian and international populations - Rapid onset of action (2–4 weeks for mood improvement, 6–8 weeks for full response) ### Why SSRIs Work in MDD SSRIs increase synaptic serotonin by blocking reuptake at the presynaptic terminal. Serotonin dysfunction is implicated in depression pathophysiology, particularly in mood regulation, sleep, and appetite control. **Clinical Pearl:** Melancholic depression (with neurovegetative symptoms like early morning awakening, appetite loss, psychomotor changes) often responds particularly well to SSRIs and tricyclic antidepressants. ### Dosing and Timeline - **Fluoxetine:** Start 20 mg/day; can increase to 40–80 mg/day if needed after 4–6 weeks - **Expected response:** Mood improvement typically begins at 2–4 weeks; full response by 8–12 weeks - **Monitoring:** Assess at 2 weeks for tolerability, then at 6–8 weeks for efficacy **Mnemonic for SSRIs:** **FLUVOXAMINE, FLUOXETINE, PAROXETINE, SERTRALINE, CITALOPRAM, ESCITALOPRAM** (F-F-P-S-C-E) — the six most common SSRIs used in MDD.