Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
Int J Neuropsychopharmacol. 2010 Feb;13(1):5-14. doi: 10.1017/S1461145709990344. Epub 2009 Jul 29.
Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression.
随机对照试验已经证明了第二代抗精神病药在治疗双相情感障碍急性躁狂中的疗效。尽管抑郁症被认为是双相情感障碍的标志，但目前尚无关于评估现代非典型抗精神病药在双相情感障碍抑郁中的疗效的系统评价或荟萃分析。我们系统地回顾了已发表或注册的现代抗精神病药治疗成人双相 I 型和/或 II 型抑郁患者（DSM-IV 标准）的随机、双盲、安慰剂对照试验（RCT）。疗效终点是根据 8 周期间蒙哥马利-阿斯伯格抑郁评定量表（MADRS）的变化来评估的。使用风险比作为效应大小，通过荟萃分析合并数据，置信区间为 95%（95%CI），统计学显著性水平为 5%（p<0.05）。我们确定了 5 项 RCT；其中 4 项涉及抗精神病药单药治疗，1 项涉及单药治疗和与抗抑郁药联合治疗。两项喹硫平试验分析了 300 和 600mg/d 两种剂量的安全性和疗效。唯一的奥氮平试验评估了 5-20mg/d 范围内的奥氮平单药治疗和 5-20mg/d 和 6-12mg/d 范围内的奥氮平-氟西汀联合治疗。两项阿立哌唑安慰剂对照试验评估了 5-30mg/d 的剂量。喹硫平和奥氮平试验（3/5，60%）显示优于安慰剂（p<0.001）。仅有 2/5（40%）（两项阿立哌唑试验）在最初的 6 周后主要疗效指标失败。一些现代抗精神病药（喹硫平和奥氮平）在双相抑郁患者中从第 1 周开始就显示出疗效。快速起效似乎是双相情感障碍中抗精神病药的一个共同特征。
