A 38-year-old woman presents to the psychiatry outpatient clinic with a 3-month history of persistent depressed mood, anhedonia, and significant weight loss (8 kg). She reports waking at 4 AM daily, unable to return to sleep, and describes her mood as worse in the early morning hours. She denies suicidal ideation but admits to feelings of worthlessness and difficulty concentrating at work. On examination, she appears psychomotor retarded with poor eye contact. Laboratory investigations including TSH, vitamin B12, and complete blood count are all normal. What is the most appropriate next step in management?

Explanation

## Diagnosis and Management of Major Depressive Disorder ### Clinical Presentation Analysis This patient meets DSM-5 criteria for Major Depressive Disorder with several **high-yield** features: | Feature | Significance | |---------|-------------| | Depressed mood + anhedonia | Core symptoms (≥2 weeks required; this patient has 3 months) | | Early morning awakening (terminal insomnia) | Suggests **melancholic features** | | Diurnal mood variation (worse in AM) | Classic melancholic pattern | | Psychomotor retardation | Objective sign supporting severity | | Feelings of worthlessness | Cognitive symptom | | Concentration difficulty | Cognitive impairment | | Weight loss | Neurovegetative symptom | **Key Point:** This patient has ≥5 symptoms present for ≥2 weeks, with functional impairment and no organic/medical cause (TSH, B12 normal). This definitively meets MDD criteria. ### Why SSRIs Are First-Line **High-Yield:** SSRIs (sertraline, escitalopram, paroxetine) are the **gold-standard first-line agents** for MDD in the absence of contraindications [cite:Kaplan & Sadock 11e Ch 8]. 1. **Efficacy**: ~60% response rate at therapeutic doses 2. **Safety profile**: Minimal cardiac/anticholinergic effects 3. **Tolerability**: Fewer side effects than TCAs or MAOIs 4. **Dosing**: Sertraline 50 mg daily is an appropriate starting dose; therapeutic range is 50–200 mg/day 5. **Timeline**: Response typically seen in 4–6 weeks; full response in 8–12 weeks ### Management Algorithm ```mermaid flowchart TD A[MDD diagnosis confirmed<br/>No suicidality]:::outcome --> B{Psychotic features?}:::decision B -->|No| C[First-line: SSRI<br/>or SNRI]:::action B -->|Yes| D[Add antipsychotic<br/>or ECT]:::action C --> E[Assess response<br/>at 4-6 weeks]:::decision E -->|Partial/No response| F[Increase dose or<br/>switch agent]:::action E -->|Full response| G[Continue 6-12 months<br/>then taper]:::action H{High suicide risk?}:::decision H -->|Yes| I[Consider ECT or<br/>hospitalization]:::urgent H -->|No| C ``` **Clinical Pearl:** Melancholic features (early morning awakening, psychomotor changes, diurnal mood variation) often respond well to SSRIs and may even benefit from augmentation with low-dose tricyclics if response is partial. **Tip:** Always assess suicide risk at baseline and during follow-up — this patient denies suicidality, so outpatient SSRI initiation is safe. ### Why Other Options Are Incorrect - **ECT immediately**: Reserved for severe depression with psychotic features, catatonia, or imminent suicide risk — not first-line here - **Alprazolam**: Benzodiazepines are NOT recommended as monotherapy for MDD; risk of dependence and masking underlying disorder - **Brain MRI**: Organic causes already ruled out by normal TSH and B12; imaging not indicated in straightforward MDD