Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
Int J Neuropsychopharmacol. 2019 Nov 1;22(11):698-709. doi: 10.1093/ijnp/pyz040.
This systematic review and meta-analysis included double-blind, randomized, placebo-controlled trials of brexpiprazole adjunctive treatment (0.5-3 mg/d) for major depressive disorder where antidepressant treatment had failed.
The outcomes were the response rate (primary), remission rate (secondary), Montgomery Åsberg Depression Rating Scale score (secondary), Sheehan Disability Scale scores (secondary), Clinical Global Impression-Improvement/Severity scores, discontinuation rate, and individual adverse events. A subgroup meta-analysis of the data at week 6 compared outcomes by dose >2 mg/d or ≤2 mg/d (2 mg/d is the recommended dose).
We identified 9 studies (n = 3391). Compared with placebo, brexpiprazole (any dose) was superior for response rate (risk ratio [RR] = 0.93, 95% confidence interval [95% CI] = 0.89-0.97, number needed to treat = 17), remission rate (RR = 0.95, 95% CI = 0.93-0.98, number needed to treat = 25), Montgomery Åsberg Depression Rating Scale score (standardized mean difference = -0.20, 95% CI = -0.29, -0.11), Sheehan Disability Scale score (standardized mean difference = -0.12, 95% CI = -0.21, -0.04), and Clinical Global Impression-Improvement/Severity scores but was associated with a higher discontinuation rate, akathisia, insomnia, restlessness, somnolence, and weight increase. Doses >2 mg/d had a significantly higher RR for response rate than ≤2 mg/d (0.96 vs 0.89); moreover, compared with placebo, doses >2 mg/d were associated with higher incidences of akathisia (RR = 4.58) and somnolence (RR = 7.56) as well as were marginally associated with a higher incidence of weight increase (RR = 3.14, P = .06). Compared with placebo, doses ≤2 mg/d were associated with higher incidences of akathisia (RR = 2.28) and weight increase (RR = 4.50).
Brexpiprazole adjunctive treatment is effective for major depressive disorder when antidepressant treatment fails. At 6 weeks, doses ≤2 mg/d presented a better risk/benefit balance than >2 mg/d.
本系统评价和荟萃分析纳入了抗抑郁药治疗失败的重度抑郁症患者中，使用布瑞哌唑（剂量为 0.5-3 毫克/天）作为辅助治疗的双盲、随机、安慰剂对照试验。
主要结局为应答率（一级）、缓解率（二级）、蒙哥马利抑郁评定量表（二级）、Sheehan 残疾量表评分（二级）、临床总体印象-改善/严重程度评分、停药率和个体不良事件。对第 6 周的数据分析进行了亚组荟萃分析，比较了剂量＞2 毫克/天和≤2 毫克/天（2 毫克/天为推荐剂量）的结局。
我们共确定了 9 项研究（n=3391）。与安慰剂相比，布瑞哌唑（任何剂量）在应答率（风险比[RR]为 0.93，95%置信区间[95%CI]为 0.89-0.97，需要治疗的人数[NNT]为 17）、缓解率（RR 为 0.95，95%CI 为 0.93-0.98，NNT 为 25）、蒙哥马利抑郁评定量表评分（标准化均数差=-0.20，95%CI=-0.29，-0.11）、Sheehan 残疾量表评分（标准化均数差=-0.12，95%CI=-0.21，-0.04）和临床总体印象-改善/严重程度评分方面均有显著优势，但停药率更高，还会导致静坐不能、失眠、不安、嗜睡和体重增加。剂量＞2 毫克/天的应答率显著高于≤2 毫克/天（RR 为 0.96 比 0.89）；此外，与安慰剂相比，剂量＞2 毫克/天与静坐不能（RR 为 4.58）和嗜睡（RR 为 7.56）的发生率增加相关，且与体重增加的发生率增加（RR 为 3.14，P=0.06）有轻微关联。与安慰剂相比，剂量≤2 毫克/天与静坐不能（RR 为 2.28）和体重增加（RR 为 4.50）的发生率增加相关。
当抗抑郁药治疗失败时，布瑞哌唑辅助治疗重度抑郁症是有效的。在 6 周时，≤2 毫克/天的剂量比＞2 毫克/天具有更好的风险/获益平衡。
