Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis
Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis
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DOI：
10.1016/s0140-6736(16)30385-3
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发表时间：
2016-08-27
期刊：
影响因子：
168.9
通讯作者：
Xie, Peng
中科院分区：
文献类型：
--
作者：
Cipriani, Andrea;Zhou, Xinyu;Xie, Peng
背景重性抑郁障碍是儿童和青少年最常见的精神障碍之一。然而，是否在这一人群中使用药物干预以及应首选哪种药物仍然存在争议。因此，我们的目的是比较和排名抗抑郁药和安慰剂的抑郁症在young people.Methods我们做了一个网络荟萃分析，以确定相关试验的直接和间接证据。我们检索了PubMed、科克伦图书馆、Web of Science、Embase、CINAHL、PsycINFO、LiLACS、监管机构网站和国际注册中心，以获得截至2015年5月31日的已发表和未发表的双盲随机对照试验，用于儿童和青少年重度抑郁障碍的急性治疗。我们纳入了阿米替林、西酞普兰、氯丙咪嗪、地昔帕明、度洛沙酮、依他普仑、氟西汀、丙咪嗪、米氮平、奈法唑酮、去甲替林、帕罗西汀、舍曲林和文拉法辛的试验。排除了招募患有难治性抑郁症、治疗持续时间少于4周或总样本量少于10例患者的参与者的试验。我们使用预定义的数据提取表从已发表的报告中提取相关信息，并使用科克伦偏倚风险工具评估偏倚风险。主要结局是疗效（抑郁症状的变化）和耐受性（因不良事件而停药）。我们使用随机效应模型进行配对荟萃分析，然后在贝叶斯框架内进行随机效应网络荟萃分析。我们使用GRADE框架评估了有助于每个网络估计的证据质量。本研究在PROSPERO注册，编号CRD 42015016023。结果我们认为34项试验合格，包括5260名参与者和14种抗抑郁治疗。在大多数比较中，证据质量被评为非常低。对于疗效，仅氟西汀的有效性在统计学上显著高于安慰剂（标准化平均差异-0.51，95%可信区间[CrI] -0.99至-0.03）。在耐受性方面，氟西汀也优于度洛沙汀（比值比[OR] 0.31，95%CrI 0.13 - 0.95）和丙咪嗪（0.23，0.04 - 0.78）。服用丙咪嗪、文拉法辛和度洛昔单抗的患者因不良事件而停药的比例高于服用安慰剂的患者（分别为5.49、1.96 - 20.86; 3.19、1.01 - 18.70; 2.80、1.20 - 9.42）。在异质性方面，全球的I-2值为33.21%的疗效和0%的tolerability.Interpretation当考虑到抗抑郁药的风险-效益的严重抑郁症的急性治疗，这些药物似乎并没有提供ER一个明确的优势，为儿童和青少年。当需要药物治疗时，氟西汀可能是最好的选择。
Background Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people.Methods We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023.Findings We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference -0.51, 95% credible interval [CrI] -0.99 to -0.03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0.31, 95% CrI 0.13 to 0.95) and imipramine (0.23, 0.04 to 0.78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5.49, 1.96 to 20.86; 3.19, 1.01 to 18.70; and 2.80, 1.20 to 9.42, respectively). In terms of heterogeneity, the global I-2 values were 33.21% for efficacy and 0% for tolerability.Interpretation When considering the risk-benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to off er a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated.