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.
Michael C Mithoefer, Allison A. Feduccia, Lisa Jerome, Anne Mithoefer, Mark T Wagner, Zach Walsh, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin
Psychopharmacology September 1, 2019 Retracted DOI: 10.1007/s00213-019-05249-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pooled analysis of six randomized, double-blind, controlled clinical trials Peer reviewed |
|---|---|
| Sample size | 103 |
| Population | Adults with posttraumatic stress disorder |
| Intervention | MDMA-assisted psychotherapy |
| Dose | 75-125 mg |
| Duration | Two or three 8-hour sessions spaced a month apart, with three non-drug 90-min therapy sessions before the first MDMA exposure and three to four after each experimental session |
| Topics | Anxiety MDMA PTSD Psychedelic-assisted therapy |
| Keywords | MDMA-Assisted Psychotherapy Posttraumatic stress disorder MDMA Alongside Therapy Active MDMA Structured psychotherapy sessions Promising treatment Novel approach PTSD Symptoms Psychedelic therapy: psychedelic Anxiety: anxiety Related anxiety |
| Citations | 364 |
| Registration | NCT00090064 NCT00353938 NCT01958593 NCT01211405 NCT01689740 NCT01793610 |
| Key findings | MDMA-assisted psychotherapy produced significantly greater reductions in PTSD symptoms and higher rates of diagnostic remission compared to placebo or low-dose control. |
Abstract
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. 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. 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. 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. ClinicalTrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.
Comparable studies
Other randomized controlled trials on MDMA for anxiety, most cited first.