A 55-year-old depressed man fails two adequate antidepressant trials. He is now on venlafaxine 225 mg/day. His psychiatrist considers augmentation. Which augmentation strategy has the strongest evidence base (Level I) for treatment-resistant depression?
- A Adding buspirone
- B Adding methylphenidate
- C Adding atypical antipsychotic (aripiprazole, quetiapine, or olanzapine-fluoxetine) ✓
- D Switching to a reversible MAOI
Correct answer: C. Adding atypical antipsychotic (aripiprazole, quetiapine, or olanzapine-fluoxetine)
Explanation
FDA-approved augmentation strategies for treatment-resistant depression include adding an atypical antipsychotic to an ongoing antidepressant. Aripiprazole, quetiapine (extended-release), and the olanzapine-fluoxetine combination (Symbyax) are specifically approved. Multiple RCTs and meta-analyses support Level I evidence for these agents. Buspirone augmentation has only modest evidence. Lithium augmentation also has strong evidence but is not FDA-approved for this indication. Stimulant augmentation and MAOIs carry limited or specialist-only evidence.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.