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Objective:  To review the literature on efficacy and risks of combining antipsychotics (atypical with atypical or conventional) and suggest a rationale and strategies for future clinical trials.

Method:  A computerized Medline search supplemented by an examination of cross‐references and reviews was performed.

Results:  Empirical evidence for the efficacy of combining antipsychotics is too limited to draw firm conclusions. The practice of augmenting clozapine with more ‘tightly bound’ D2 receptor antagonists as exemplified by risperidone augmentation of clozapine has some empirical and theoretical support. The risks of augmentation strategies have not been studied systematically. No study has examined the economic impact of combination treatment.

Conclusion:  Further trials of antipsychotic combination therapies are needed before this currently unsupported practice can be recommended. Rationales for …