The Zucker Hillside Hospital, Psychiatry Research, North Shore LIJ Health System, Glen Oaks, NY 11004, USA.
Expert Opin Drug Saf. 2012 Jul;11(4):527-42. doi: 10.1517/14740338.2012.683523. Epub 2012 May 8.
Antipsychotic polypharmacy (APP), the concomitant use of ≥ 2 antipsychotics, is common in clinical practice. Prior reviews have focused on the efficacy of APP, but no systematic review exists regarding the safety and tolerability of this practice.
A systematic review of adverse effects associated with APP was conducted to prepare this review; case series with ≥ 2 patients, chart reviews, naturalistic, database, cohort and randomized studies that reported on the association between APP in general or specific APP combinations and global or specific adverse effect were included. Methodological limitations of available studies are discussed and recommendations for clinicians and future research are provided.
Across mostly small and uncontrolled studies, APP has been associated with increased global side effect burden, rates of Parkinsonian side effects, anticholinergic use, hyperprolactinemia, sexual dysfunction, hypersalivation, sedation/somnolence, cognitive impairment and diabetes. Effects on akathisia and mortality were inconclusive. Although some combinations, particularly aripiprazole augmentation of an agent with greater side effect burden, may reduce weight gain, dyslipidemia, hyperprolactinemia and sexual dysfunction, APP should remain a last-resort treatment option after monotherapy, switching and non-antipsychotic combinations have failed. More data are needed to further inform the individualized risk-benefit evaluation of APP.
抗精神病药联合用药（APP），即同时使用≥2 种抗精神病药，在临床实践中很常见。先前的综述主要关注 APP 的疗效，但尚无关于这种治疗方法的安全性和耐受性的系统评价。
为撰写这篇综述，我们对 APP 相关不良事件进行了系统评价；纳入了病例系列研究（≥2 例患者）、图表回顾、自然主义研究、数据库研究、队列研究和随机研究，这些研究报告了 APP 一般或特定 APP 联合用药与总体或特定不良事件之间的关联。讨论了现有研究的方法学局限性，并为临床医生和未来研究提供了建议。
在大多数小型和非对照研究中，APP 与总体不良事件负担增加、帕金森副作用、抗胆碱能药物使用、高催乳素血症、性功能障碍、唾液分泌过多、镇静/嗜睡、认知障碍和糖尿病的发生率增加有关。关于静坐不能和死亡率的影响尚无定论。虽然某些组合，特别是增效治疗，可能会降低体重增加、血脂异常、高催乳素血症和性功能障碍的风险，但 APP 应仅作为单药治疗、药物转换和非抗精神病药物联合治疗失败后的最后治疗选择。需要更多的数据来进一步告知 APP 的个体化风险效益评估。
