Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using ‘A MeaSurement Tool to Assess systematic Reviews’ Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the ‘Grading of Recommendations, Assessment, Development and Evaluations’ (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4–8 weeks) and tamoxifen (for response and symptoms reduction at 4–6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6–8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research.

之前在临床试验中测试并批准用于不同适应症的几种药物已被重新用于双相情感障碍。我们对随机安慰剂对照试验的荟萃分析进行了系统的荟萃审查，调查将重新利用的药物作为躁狂症和双相抑郁症的辅助治疗。我们使用“用于评估系统评价的测量工具”第 2 版 (AMSTAR 2) 进行了严格的评估。我们综合了疗效、耐受性和安全性的结果，根据“推荐、评估、开发和评估分级”（GRADE）方法评估证据质量。我们的系统搜索确定了九项符合条件的研究，调查了 12 种药物，其中 4 项针对躁狂症，8 项针对双相抑郁症。根据 AMSTAR 2，报告质量参差不齐。在躁狂症中，别嘌醇（用于 4-8 周的症状减轻和缓解）和他莫昔芬（用于 4-6 周的缓解和症状减轻）显示出比安慰剂更高的疗效，分别具有低和极低的证据质量。关于双相抑郁症，莫达非尼/阿莫达非尼（用于 6-8 周的反应、缓解和症状减轻）和普拉克索（用于 6 周的反应和症状减轻）优于安慰剂，尽管证据质量低。塞来昔布和 N-乙酰半胱氨酸疗效的结果质量低下，仅限于某些结果。总体而言，由于缺乏高质量和中等质量的证据，我们无法就重新利用药物作为躁狂症和双相抑郁症的辅助治疗的临床效用得出确切的结论，这突出了进一步研究的必要性。