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.
Study Goal
The researchers aimed to evaluate the efficacy and safety of MDMA-assisted psychotherapy for treating PTSD and determine the optimal study design for phase 3 trials.
Results Summary
MDMA-assisted psychotherapy significantly reduced PTSD symptoms compared to placebo, with a large treatment effect (Cohen's d = 0.8). Over half of the active group no longer met PTSD diagnostic criteria after treatment, and depression symptoms also improved, though the latter only trended toward significance.
Population
Adults with PTSD.
Effective Dosage
75-125 mg MDMA in two or three 8-hour sessions spaced a month apart.
Duration
Two or three experimental sessions, each spaced a month apart, with additional non-drug therapy sessions before and after.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
MDMA-assisted psychotherapy | decrease | CAPS-IV total scores | individuals with PTSD | MMRM estimated mean difference (SE) between groups -22.0 (5.17) | significantly greater reductions | #1 |
MDMA-assisted psychotherapy | decrease | CAPS-IV PTSD diagnostic criteria | individuals with PTSD | 54.2% vs 22.6% | more participants did not meet diagnostic criteria | #2 |
MDMA-assisted psychotherapy | decrease | Depression symptom on the BDI-II | individuals with PTSD | MMRM estimated mean difference (SE) between groups -6.0 (3.03) | improvement was greatest | #3 |
All doses of MDMA | no change | tolerability | individuals with PTSD | - | well tolerated | #4 |
MDMA-assisted psychotherapy | decrease | PTSD symptoms | adults with PTSD | - | efficacious and well tolerated | #5 |
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.