Objectives To characterize individual participant level response distributions to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration from 1979 to 2016. Design Individual participant data analysis. Population 232 randomized, double blind, placebo controlled trials of drug monotherapy for major depressive disorder submitted by drug developers to the FDA between 1979 and 2016, comprising 73 388 adult and child participants meeting the inclusion criteria for efficacy studies on antidepressants. Main outcome measures Responses were converted to Hamilton Rating Scale for Depression (HAMD17) equivalent scores where other measures were used to assess efficacy. Multivariable analyses examined the effects of age, sex, baseline severity, and year of the study on improvements in depressive symptoms in the antidepressant and placebo groups. Response distributions were analyzed with finite mixture models. Results The random effects mean difference between drug and placebo favored drug (1.75 points, 95% confidence interval 1.63 to 1.86). Differences between drug and placebo increased significantly (P<0.001) with greater baseline severity. After controlling for participant characteristics at baseline, no trends in treatment effect or placebo response over time were found. The best fitting model of response distributions was three normal distributions, with mean improvements from baseline to end of treatment of 16.0, 8.9, and 1.7 points. These distributions were designated Large, Non-specific, and Minimal responses, respectively. Participants who were treated with a drug were more likely to have a Large response (24.5% v 9.6%) and less likely to have a Minimal response (12.2.% v 21.5%). Conclusions The trimodal response distributions suggests that about 15% of participants have a substantial antidepressant effect beyond a placebo effect in clinical trials, highlighting the need for predictors of meaningful responses specific to drug treatment. No additional data available.

中文翻译：

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在提交给美国食品和药物管理局的随机、安慰剂对照试验中对重度抑郁症急性单药治疗的反应：个体参与者数据分析

目的 在 1979 年至 2016 年提交给美国食品和药物管理局的随机、安慰剂对照试验中，表征个体参与者对重度抑郁症急性单药治疗的反应分布。设计个体参与者数据分析。1979 年至 2016 年间，药物开发商向 FDA 提交了 232 项针对重度抑郁症的药物单一疗法的随机、双盲、安慰剂对照试验，其中包括 73 388 名成人和儿童参与者，符合抗抑郁药疗效研究的纳入标准。主要结果测量 反应被转换为汉密尔顿抑郁评定量表 (HAMD17) 等效分数，其中使用其他测量来评估疗效。多变量分析检查了年龄、性别、基线严重程度、抗抑郁药和安慰剂组抑郁症状改善的研究年份。使用有限混合模型分析响应分布。结果 药物和安慰剂偏爱药物之间的随机效应平均差异（1.75 分，95% 置信区间 1.63 至 1.86）。药物和安慰剂之间的差异随着基线严重程度的增加而显着增加（P<0.001）。在控制基线时的参与者特征后，没有发现随时间推移治疗效果或安慰剂反应的趋势。反应分布的最佳拟合模型是三个正态分布，从基线到治疗结束的平均改善分别为 16.0、8.9 和 1.7 分。这些分布分别被指定为大响应、非特定响应和最小响应。接受药物治疗的参与者更有可能有较大的反应（24.5% 对 9.6%），不太可能有最小的反应（12.2.% 对 21.5%）。结论 三峰反应分布表明，在临床试验中，约 15% 的参与者具有超越安慰剂效应的显着抗抑郁作用，突出了对药物治疗特有的有意义反应的预测因子的需求。没有可用的额外数据。