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
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
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DOI：
10.1007/s00213-019-05249-5
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发表时间：
2019-09-01
影响因子：
3.4
通讯作者：
Doblin, Rick
中科院分区：
文献类型：
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作者：
Mithoefer, Michael C.;Feduccia, Allison A.;Doblin, Rick
背景 创伤后应激障碍是一种普遍存在的心理健康状况，对日常功能产生重大影响，但缺乏足够的治疗选择。在这里，我们通过汇总分析评估了六项 2 期试验，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 月在五个研究中心进行了六项随机、双盲、对照临床试验。在手动心理治疗过程中，对 PTSD 患者给予活性剂量的 MDMA（75-125 mg，n = 72）或安慰剂/对照剂量（0-40 mg，n = 31），分两到三个 8 小时的疗程，间隔一个月。在第一次 MDMA 暴露之前进行 3 次 90 分钟的非药物治疗，每个实验疗程后进行 3 到 4 次。结果 经过两次盲法实验后，活动组的 CAPS-IV 总分相对于基线的下降显着大于对照组 [MMRM 估计组间平均差 (SE) - 22.0 (5.17)，P < 0.001]。组间 Cohen's d 效应大小为 0.8，表明治疗效果很大。经过两次实验后，活动组中不符合 CAPS-IV PTSD 诊断标准的参与者 (54.2%) 多于对照组 (22.6%)。与对照组相比，BDI-II 上的抑郁症状改善最大，尽管仅趋向于显着的组间差异 [MMRM，组间估计平均差 (SE) - 6.0 (3.03)，P = 0.053]。所有剂量的 MDMA 均具有良好的耐受性，在实验期间和随后的 7 天中，活性 MDMA 组出现一些预期反应的频率更高。结论 MDMA 辅助心理治疗在大样本 PTSD 成人中有效且耐受性良好。这些研究支持扩展到 3 期试验，并导致 FDA 授予这种有前景的治疗方法突破性疗法称号。
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.