A patient with treatment-resistant schizophrenia (TRS) is started on clozapine. After 8 weeks at adequate plasma levels (>350 ng/mL), he continues to have significant positive symptoms. The evidence-based augmentation strategy with the strongest support is:
- A Switching to risperidone
- B Adding lithium
- C Adding amisulpride to clozapine ✓
- D Adding haloperidol
Correct answer: C. Adding amisulpride to clozapine
Explanation
For clozapine-resistant schizophrenia, augmentation with amisulpride (a selective D2/D3 blocker) has the strongest evidence base among antipsychotic combinations, with multiple RCTs showing significant reduction in positive symptoms. This 'clozapine + amisulpride' combination is the most evidence-based augmentation strategy. Adding another typical antipsychotic (haloperidol) increases EPS risk without clear benefit. Lithium augments mood symptoms but lacks evidence for positive symptoms.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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