Placebo response rates in antidepressant trials: a systematic review of published and unpublished double-blind randomised controlled studies
Placebo response rates in antidepressant trials: a systematic review of published and unpublished double-blind randomised controlled studies
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DOI：
10.1016/s2215-0366(16)30307-8
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发表时间：
2016-11-01
影响因子：
64.3
通讯作者：
Salanti, Georgia
中科院分区：
文献类型：
--
作者：
Furukawa, Toshi A.;Cipriani, Andrea;Salanti, Georgia
先前的研究表明，自20世纪70年代以来，抗抑郁药物试验中安慰剂的反应率一直在增加。然而，这些研究基于过时或有限的数据集，并使用了不适当的统计方法。我们对抗抑郁药的安慰剂对照随机对照试验进行了系统回顾，以检查安慰剂反应率与研究和患者特征之间的关系。在本系统综述中，我们检索了已发表和未发表的第一代和第二代抗抑郁药用于成人重度抑郁症急性治疗的双盲随机安慰剂对照试验（更新：2016年1月8日）。每年对安慰剂反应的对数转换比例（定义为抑郁严重程度评分较基线降低50%或以上）进行meta分析合成。然后，我们在这些特征的长期变化中寻找结构断点，并通过meta回归检查研究年份、其他试验和患者特征对反应率的影响。我们确定了1978年至2015年间进行的252项安慰剂对照试验（26324名安慰剂患者）。1991年出现了结构性突破，从那时起，抗抑郁药试验中安慰剂的平均反应率一直保持在35%到40%之间（相对风险[RR] 1.00, 95% CI 0.97-1.03, p= 0.99，每5年增加一次）。研究的长度和研究中心的数量是显著因素（试验长度超过1周，RR 1.03, 95% CI 1.01-1.05；多中心与单中心试验分别为1.32、1.11-1.57）。与人们普遍认为的相反，在抗抑郁药物试验中，安慰剂的平均反应率已经稳定了超过25年。从临床和方法学的角度来看，这一新证据应该会对科学文献的解释和精神药理学的未来产生影响。
Background Previous studies have shown that placebo response rates in antidepressant trials have been increasing since the 1970s. However, these studies have been based on outdated or limited datasets and have used inappropriate statistical methods. We did a systematic review of placebo-controlled randomised controlled trials of antidepressants to examine associations between placebo-response rates and study and patient characteristics.Methods In this systematic review, we searched for published and unpublished double-blind randomised placebocontrolled trials of first-generation and second-generation antidepressants for acute treatment of major depression in adults (update: Jan 8, 2016). The log-transformed proportions of placebo response, defined as 50% or greater reduction in depression severity score from baseline, were meta-analytically synthesised for each year. We then looked for a structural break point in the secular changes in these characteristics through the years and examined the influence of the study year and other trial and patient characteristics on the response rates through meta-regression.Findings We identified 252 placebo-controlled trials (26 324 patients on placebo) done between 1978 and 2015. There was a structural break in 1991, and since then, the average placebo response rates in antidepressant trials have remained constant in the range between 35% and 40% (relative risk [RR] 1.00, 95% CI 0.97-1.03, p= 0.99, for every 5-year increase). The length of the study and the number of study centres were significant factors (RR 1.03, 95% CI 1.01-1.05 for 1 more week in trial length; 1.32, 1.11-1.57 for multicentre vs single-centre trials).Interpretation Contrary to the widely held belief, the average placebo response rates in antidepressant trials have been stable for more than 25 years. This new evidence should have an effect on the interpretation of the scientific literature and the future of psychopharmacology, both from a clinical and methodological point of view.