Department of Psychiatry, 2129University of Calgary, Alberta, Canada.
Department of Public Health Sciences, 4257Queen's University, Kingston, Ontario, Canada.
Can J Psychiatry. 2021 Mar;66(3):274-288. doi: 10.1177/0706743720970857. Epub 2020 Nov 11.
We investigated the comparative efficacy and tolerability of augmentation strategies for bipolar depression.
We conducted a systematic review and network meta-analysis of 8 electronic databases for double-blind, randomized controlled trials of adjunctive pharmacotherapies for acute bipolar depression.
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and applied the Cochrane risk of bias tool for study quality appraisal. Two reviewers independently abstracted data. We resolved all discrepancies by consensus.
Primary outcomes were response and completion of treatment. We estimated summary rate ratios (RRs) and standardized mean differences (SMDs) relative to placebo controls using frequentist random-effects network meta-analysis.
We identified 69 trials meeting eligibility criteria (8,007 participants, 42.8 years, 58.0% female). Adjunctive racemic intravenous ketamine, coenzyme Q10, pramipexole, fluoxetine, and lamotrigine were more effective than placebo. Summary RRs for response ranged between 1.51 (95% confidence interval [CI], 1.11 to 2.06) for fluoxetine and 12.49 (95% CI, 3.06 to 50.93) for racemic intravenous ketamine. For completion of treatment, risperidone appeared less tolerable than placebo (RR = 0.59; 95% CI, 0.38 to 0.94), while fluoxetine seemed more tolerable than placebo (RR = 1.13; 95% CI, 1.02 to 1.24). None of the investigated agents were associated with increased treatment-emergent mood switches.
The evidence for augmentation strategies in bipolar depression is limited to a handful of agents. Fluoxetine appeared to have the most consistent evidence base for both efficacy and tolerability. There remains a need for additional research exploring novel treatment strategies for bipolar depression, particularly head-to-head studies.
我们研究了双相抑郁增效策略的比较疗效和耐受性。
我们对 8 个电子数据库进行了系统评价和网络荟萃分析，以评估急性双相抑郁的附加药物治疗的双盲、随机对照试验。
我们遵循系统评价和荟萃分析的首选报告项目，并应用 Cochrane 偏倚风险工具评估研究质量。两位审查员独立提取数据。我们通过共识解决了所有差异。
主要结局是反应和治疗完成。我们使用频率随机效应网络荟萃分析，相对于安慰剂对照，估计综合率比（RR）和标准化均数差（SMD）。
我们确定了符合资格标准的 69 项试验（8007 名参与者，平均年龄 42.8 岁，58.0%为女性）。辅助性外消旋静脉注射氯胺酮、辅酶 Q10、普拉克索、氟西汀和拉莫三嗪比安慰剂更有效。反应的综合 RR 范围从氟西汀的 1.51（95%置信区间[CI]，1.11 至 2.06）到外消旋静脉注射氯胺酮的 12.49（95%CI，3.06 至 50.93）。对于治疗完成，利培酮似乎比安慰剂耐受性差（RR=0.59；95%CI，0.38 至 0.94），而氟西汀似乎比安慰剂耐受性更好（RR=1.13；95%CI，1.02 至 1.24）。没有一种被调查的药物与治疗引起的情绪变化增加有关。
双相抑郁增效策略的证据仅限于少数几种药物。氟西汀在疗效和耐受性方面似乎有最一致的证据基础。需要进一步研究探索双相抑郁的新治疗策略，特别是头对头研究。
