A 38-year-old woman with recurrent major depression is started on fluoxetine. After 4 weeks, she remains symptomatic. Her Hamilton Depression Rating Scale score is unchanged. What is the MOST appropriate next pharmacological strategy according to evidence-based guidelines?

• A Switch to a TCA
• B Add lithium augmentation immediately
• C Switch to an SNRI
• D Increase fluoxetine dose and reassess at 8 weeks ✓

Explanation

An adequate antidepressant trial requires at least 4–6 weeks at a therapeutic dose before assessing response. After only 4 weeks without dose optimization, the first step is to increase the fluoxetine dose to ensure an adequate therapeutic trial. The full antidepressant effect typically takes 6–8 weeks. If there is still no response after an adequate dose and duration (8 weeks), then switching to another agent (e.g., SNRI) or augmentation strategies like lithium or atypical antipsychotics are appropriate next steps. Immediate augmentation at 4 weeks is premature.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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Written and medically reviewed by the StethoPrep medical team.