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临床试验中仅15%的重度抑郁症患者接受急性单一疗法后有效缓解
作者:小柯机器人 发布时间:2022/8/6 23:39:49

美国约翰霍普金斯大学医学院Brian J Miller团队研究了美国食品和药物管理局的随机对照安慰剂试验中,重度抑郁症急性单一疗法的治疗响应。相关论文于2022年8月2日发表在《英国医学杂志》上。

为了在1979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,描述个体参与者对重度抑郁症急性单一疗法的响应分布情况,研究组进行了一项个人参与者的数据分析。1979至2016年间,药物开发商向FDA提交了232项针对重度抑郁症的单药治疗的随机、双盲、安慰剂对照试验,包括73388名符合抗抑郁药疗效研究纳入标准的成人和儿童参与者。

治疗响应被转换为汉密尔顿抑郁评定量表(HAMD17)等效分数,其他方法被用于评估疗效。多变量分析考察了年龄、性别、基线严重程度和研究年份对抗抑郁药组和安慰剂组抑郁症状改善的影响。用有限混合模型分析响应分布。

抗抑郁药和安慰剂之间的随机效应平均差异为1.75分,偏好药物组。药物和安慰剂之间的差异随着基线严重程度的增加而显著增加。在基线时控制参与者特征后,未发现治疗效果或安慰剂响应随时间的变化趋势。响应分布的最佳拟合模型为三个正态分布,从基线到治疗结束的平均改善率分别为16.0、8.9和1.7分。这些分布分别被指定为大响应、非特异性响应和最小响应。接受药物治疗的受试者更有可能出现大响应(24.5%比9.6%),而很少出现小响应(12.2%比21.5%)。

三峰响应分布表明,在临床试验中,约15%的受试者接受治疗后具有显著的抗抑郁作用,超过安慰剂效应,这突出表明需要预测药物治疗的有意义响应。

附:英文原文

Title: Response to acute monotherapy for major depressive disorder in randomized, placebo controlled trials submitted to the US Food and Drug Administration: individual participant data analysis

Author: Marc B Stone, Zimri S Yaseen, Brian J Miller, Kyle Richardville, Shamir N Kalaria, Irving Kirsch

Issue&Volume: 2022/08/02

Abstract:

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 73388 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.

DOI: 10.1136/bmj-2021-067606

Source: https://www.bmj.com/content/378/bmj-2021-067606

期刊信息

BMJ-British Medical Journal:《英国医学杂志》,创刊于1840年。隶属于BMJ出版集团,最新IF:27.604
官方网址:http://www.bmj.com/
投稿链接:https://mc.manuscriptcentral.com/bmj