Switching from Antipsychotic Polypharmacy to Monotherapy

Several routes lead to antipsychotic polypharmacy, including efforts to optimize antipsychotic effectiveness while minimizing harms from adverse effects, or even capitalizing on these (e.g., sleepiness) for therapeutic advantage. Most clinicians assume that monotherapy is associated with better adherence, fewer adverse effects, and lower cost than polypharmacy. To examine the risks and benefits of switching from antipsychotic polypharmacy to monotherapy, investigators conducted an open-label, multisite, 6-month study (with blinded raters). The researchers randomized 127 patients with schizophrenia taking two antipsychotics (typical or atypical) to continue their current medications or to discontinue one medication.

All enrolled patients were open to changing their medications. For those randomized to monotherapy, physicians and patients decided together which antipsychotic to discontinue. Discontinuations had to be completed within 30 days. At 6 months, the groups did not differ in positive and negative symptoms, adverse effects, or hospitalization rates. Body-mass index decreased significantly in patients switched to monotherapy, whereas patients on polypharmacy showed a trend toward weight gain (P=0.05). However, more disruptions of care occurred among those switched to monotherapy. By 6 months, 86% of the polypharmacy group remained on both medications, whereas only 69% of the monotherapy group were still taking the medication initially prescribed (of those who were not, most had returned to their original regimen).