Antipsychotic polypharmacy: is there evidence for its use?

Antipsychotic polypharmacy occurs frequently in clinical practice; however, there is a lack of controlled clinical studies testing the efficacy of the combinations used. The purpose of this literature review was to examine studies and other reports that have assessed the incremental benefits and deficits of combination antipsychotic therapy versus monotherapy. A PUBMED search covering a 26-year period from 1976 to 2002 was conducted. The search was limited to clinical trials, case series, and reports. Fifty-two reports were identified that systematically assessed the efficacy of combination therapy as opposed to monotherapy: 4 double-blind studies, 13 open-label clinical trials, and 35 case reports. Only one open-label trial and 2 case reports met the design criteria of having trials of each medication and the combination in the same patients and using some type of standardized assessment to evaluate outcome. The most frequent combination was clozapine-risperidone. Of the clinical trials, 75% (3/4) of the double-blind studies and 69% (9/13) of the open-label trials found that combination therapy was effective in reducing symptoms, while 37% (13/35) of case reports documented an overall positive outcome. Currently, the clinical practice of antipsychotic polypharmacy is not evidence-based; however, there is also no evidence against its use. Expanded systematic research to assess this clinical practice is needed.