基于 6 项 2 期随机对照试验的汇总分析，MDMA 辅助心理治疗治疗 PTSD：3 期试验的研究设计和原理。
MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.
机构信息
Medical University of South Carolina, Charleston, SC, USA.
MAPS Public Benefit Corporation, 1115 Mission St, Santa Cruz, CA, USA.
出版信息
Psychopharmacology (Berl). 2019 Sep;236(9):2735-2745. doi: 10.1007/s00213-019-05249-5. Epub 2019 May 7.
BACKGROUND
Posttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.
METHODS
Six randomized, double-blind, controlled clinical trials at five study sites were conducted from April 2004 to February 2017. Active doses of MDMA (75-125 mg, n = 72) or placebo/control doses (0-40 mg, n = 31) were administered to individuals with PTSD during manualized psychotherapy sessions in two or three 8-h sessions spaced a month apart. Three non-drug 90-min therapy sessions preceded the first MDMA exposure, and three to four followed each experimental session.
RESULTS
After two blinded experimental sessions, the active group had significantly greater reductions in CAPS-IV total scores from baseline than the control group [MMRM estimated mean difference (SE) between groups - 22.0 (5.17), P < 0.001]. The between-group Cohen's d effect size was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet CAPS-IV PTSD diagnostic criteria than the control group (22.6%). Depression symptom improvement on the BDI-II was greatest for the active group compared to the control group, although only trended towards significant group differences [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated, with some expected reactions occurring at greater frequency for the active MDMA group during experimental sessions and the 7 days following.
CONCLUSIONS
MDMA-assisted psychotherapy was efficacious and well tolerated in a large sample of adults with PTSD. These studies supported expansion into phase 3 trials and led to FDA granting Breakthrough Therapy designation for this promising treatment.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.
背景
创伤后应激障碍是一种普遍存在的心理健康状况，对日常功能有重大影响，但治疗选择有限。在这里，我们对六项 2 期试验进行了汇总分析，以确定 MDMA 辅助心理治疗 PTSD 的 3 期试验的研究设计。
方法
2004 年 4 月至 2017 年 2 月，在五个研究地点进行了六项随机、双盲、对照临床试验。在间隔一个月的两次或三次 8 小时手动心理治疗疗程中，给 PTSD 个体施用 MDMA（75-125mg，n=72）或安慰剂/对照剂量（0-40mg，n=31）。在第一次 MDMA 暴露前进行三次非药物 90 分钟治疗疗程，在每次实验疗程后进行三至四次疗程。
结果
在两次盲法实验疗程后，与对照组相比，实验组的 CAPS-IV 总分从基线显著降低[MMRM 组间估计平均差异（SE）-22.0（5.17），P<0.001]。组间 Cohen's d 效应大小为 0.8，表明治疗效果显著。在两次实验疗程后，实验组中（54.2%）有更多的参与者不符合 CAPS-IV PTSD 诊断标准，而对照组中（22.6%）符合。与对照组相比，BDI-II 的抑郁症状改善在实验组中最大，尽管只有显著的组间差异趋势[MMRM，组间估计平均差异（SE）-6.0（3.03），P=0.053]。所有剂量的 MDMA 均耐受良好，在实验疗程和之后的 7 天内，实验组的一些预期反应发生频率更高。
结论
在大量 PTSD 成年患者中，MDMA 辅助心理治疗是有效且耐受良好的。这些研究支持进入 3 期试验，并导致 FDA 授予该有前途治疗方法突破性治疗指定。
试验注册
ClinicalTrials.gov 标识符：NCT00090064、NCT00353938、NCT01958593、NCT01211405、NCT01689740、NCT01793610。
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