New York State Psychiatric Institute, New York, NY 10032, USA.
Am J Psychiatry. 2011 Jul;168(7):702-8. doi: 10.1176/appi.ajp.2011.10060908. Epub 2011 May 2.
This randomized trial addressed the risks and benefits of staying on antipsychotic polypharmacy or switching to monotherapy.
Adult outpatients with schizophrenia taking two antipsychotics (127 participants across 19 sites) were randomly assigned to stay on polypharmacy or switch to monotherapy by discontinuing one antipsychotic. The trial lasted 6 months, with a 6-month naturalistic follow-up. Kaplan-Meier and Cox regression analyses examined time to discontinuation of assigned antipsychotic treatment, and random regression models examined additional outcomes over time.
Patients assigned to switch to monotherapy had shorter times to all-cause treatment discontinuation than those assigned to stay on polypharmacy. By month 6, 86% (N=48) of those assigned to stay on polypharmacy were still taking both medications, whereas 69% (N=40) of those assigned to switch to monotherapy were still taking the same medication. Most monotherapy discontinuations entailed returning to the original polypharmacy. The two groups did not differ with respect to psychiatric symptoms or hospitalizations. On average, the monotherapy group lost weight, whereas the polypharmacy group gained weight.
Discontinuing one of two antipsychotics was followed by treatment discontinuation more often and more quickly than when both antipsychotics were continued. However, two-thirds of participants successfully switched, the groups did not differ with respect to symptom control, and switching to monotherapy resulted in weight loss. These results support the reasonableness of prescribing guidelines encouraging trials of antipsychotic monotherapy for individuals receiving antipsychotic polypharmacy, with the caveat that patients should be free to return to polypharmacy if an adequate trial on antipsychotic monotherapy proves unsatisfactory.
本随机试验旨在探讨继续使用抗精神病药联合治疗或转为单药治疗的风险和获益。
19 个试验点共纳入 127 名服用两种抗精神病药的精神分裂症成年门诊患者，随机分为继续联合治疗组或停用一种抗精神病药转为单药治疗组。试验持续 6 个月，随后进行 6 个月的自然随访。Kaplan-Meier 分析和 Cox 回归分析评估了两组患者分配的抗精神病药物治疗停药时间，随机回归模型分析了随时间变化的其他结局。
与继续联合治疗组相比，转为单药治疗组患者的所有原因停药时间更短。到第 6 个月，继续联合治疗组中 86%（N=48）的患者仍同时服用两种药物，而转为单药治疗组中 69%（N=40）的患者仍服用同一种药物。大多数单药治疗的停药涉及恢复到最初的联合治疗。两组患者在精神症状或住院治疗方面无差异。平均而言，单药治疗组体重减轻，而联合治疗组体重增加。
停用两种抗精神病药中的一种比继续使用两种抗精神病药更常且更快导致治疗停药。然而，三分之二的患者成功转换，两组在症状控制方面无差异，而转为单药治疗导致体重减轻。这些结果支持为接受抗精神病药联合治疗的患者开具鼓励抗精神病药单药治疗试验的指南具有合理性，但有一个前提是，如果抗精神病药单药治疗的充分试验结果不理想，患者应可自由转回联合治疗。
