Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.
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DOI：
10.1016/s0140-6736(17)32802-7
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发表时间：
2018-04-07
期刊：
影响因子：
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通讯作者：
Geddes JR
中科院分区：
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作者：
Cipriani A;Furukawa TA;Salanti G;Chaimani A;Atkinson LZ;Ogawa Y;Leucht S;Ruhe HG;Turner EH;Higgins JPT;Egger M;Takeshima N;Hayasaka Y;Imai H;Shinohara K;Tajika A;Ioannidis JPA;Geddes JR
严重抑郁障碍是全世界成年人中最常见、负担最重、费用最高的精神疾病之一。药物治疗和非药物治疗是可用的；然而，由于资源不足，抗抑郁药物的使用比心理干预更频繁。这些药物的处方应以可获得的最佳证据为依据。因此，我们的目标是更新和扩展我们之前的工作，对成人单相重度抑郁障碍的急性治疗的抗抑郁药进行比较和排名。我们进行了系统回顾和网络荟萃分析。我们检索了Cochrane Central Register of Control Trials，CINAHL，Embase，Lilacs数据库，MEDLINE，MEDLINE in-Process，SqucINFO，监管机构的网站，以及从研究开始到2016年1月8日已发表和未发表的双盲随机对照试验的国际登记。我们纳入了21种抗抑郁药物的安慰剂对照和面对面试验，这些药物用于根据标准操作标准诊断为严重抑郁障碍的成人(≥，18岁和男女)的急性治疗。我们排除了不完全或包括20%或更多双相情感障碍、精神性抑郁或难治性抑郁的参与者或严重伴随疾病的患者的准随机试验和试验。我们按照预定义的层次结构提取数据。在网络荟萃分析中，我们使用了组水平的数据。我们根据Cochrane干预措施系统回顾手册和使用建议评级评估、发展和评估框架的证据确定性来评估研究的偏差风险。主要结果是疗效(应答率)和可接受性(因任何原因停止治疗)。我们使用具有随机效应的成对和网络荟萃分析来估计汇总优势比(OR)。这项研究已在Propero注册，编号为CRD42012002291。我们确定了28项 552的引用，其中包括522项试验，涉及116名 477参与者。就疗效而言，所有抗抑郁药都比安慰剂有效，其OR值分别为阿米替林2.13(95%可信区间1·89-2.41)和瑞波西汀1.37(1.16-1.63)。在可接受性方面，只有阿莫美拉汀(OR 0·84，95%CRI 0·72~0·97)和氟西汀(0·88，0·80~0·96)比安慰剂更少的辍学率，而氯丙咪嗪比安慰剂(1·30，1·01-1·68)更差。当考虑所有试验时，抗抑郁药疗效的OR值差异在1.15到1.55之间，可接受性的OR值在0.到0.83之间，大多数比较分析中存在较大的可信区间。在一对一的研究中，奥格莫拉汀、阿米替林、艾司匹林、米氮平、帕罗西汀、文拉法辛和伏替西汀的疗效优于其他抗抑郁药物(OR值为1.19~1.96)，而氟西汀、氟伏沙明、瑞波西汀和曲唑酮的疗效最差(OR值为0.51~0.84)。在可接受性方面，阿莫拉汀、西酞普兰、艾司匹兰、氟西汀、舍曲林和伏替西汀的耐受性高于其他抗抑郁药(OR值为0.43~0.77)，而阿米替林、氯米帕明、度洛西汀、氟伏沙明、瑞波西汀、曲唑酮和文拉法辛的脱落率最高(1.30~2.32)。在522项试验中，46项(9%)被评为高偏见风险，380项(73%)被评为中度偏见，96项(18%)被评为低风险；证据的确定性为中等到极低。在患有严重抑郁障碍的成年人中，所有的抗抑郁药都比安慰剂更有效。当分析中包括安慰剂对照试验时，活性药物之间的差异较小，而在正面对照试验中，有效性和可接受性方面的差异更大。这些结果应该为循证实践服务，并让患者、医生、指南制定者和政策制定者了解不同抗抑郁药的相对优点。国家健康研究所、牛津健康生物医学研究中心和日本科学促进会。
Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72–0·97) and fluoxetine (0·88, 0·80–0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01–1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.