Antipsychotic Polypharmacy: A Dirty Little Secret or a Fashion?

The term polypharmacy was originally coined to refer to problems related to multiple drug consumption and excessive drug use during the treatment of a disease or disorder. In the treatment of schizophrenia, polypharmacy usually refers to the simultaneous use of 2 or more antipsychotic medications or combined (adjunct) medications such as mood stabilizers, antidepressants, anxiolytics, or hypnotics in addition to single or multiple antipsychotics. Two decades ago, antipsychotic polypharmacy was criticized as being more expensive, having unproven efficacy, and causing more side effects. However, in recent years, antipsychotic polypharmacy has become more or less acceptable in the views of clinical practitioners and academic researchers. Results from recent reviews have suggested that the common practice of antipsychotic polypharmacy lacks double-blind or high-quality evidence of efficacy, except for negative symptom reduction with aripiprazole augmentation. We reviewed some representative studies that enrolled large numbers of patients and compared antipsychotic polypharmacy and monotherapy during the past decade. The results revealed that a certain proportion of select patients can benefit from antipsychotic polypharmacy without further negative consequences. Because most of the current treatment guidelines from different countries and organizations prefer monotherapy and discourage all antipsychotic polypharmacy, guidelines regarding the use of antipsychotic polypharmacy in clinical practice should be revised. On the basis of the findings of 2 large-scale studies from Asia and Europe, we also suggest ideal rates of various maintenance treatments of schizophrenia, which are as follows: antipsychotic polypharmacy, 30%; combined mood stabilizer, 15%; combined antidepressant, 10%; combined anxiolytics, 30%; and combined hypnotic, 10%.