MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled phase 3 clinical trial
PubMed 37709999 · doi:10.1038/s41591-023-02565-4
What was done
This multi-site, randomized, double-blind, confirmatory phase 3 trial evaluated the efficacy and safety of MDMA-assisted therapy (MDMA-AT) versus placebo with identical psychotherapy in 104 adults with moderate (26.9%) or severe (73.1%) post-traumatic stress disorder (PTSD). Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Primary and key secondary endpoints were changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score and Sheehan Disability Scale (SDS) functional impairment score, assessed by blinded independent raters.
What was found
MDMA-AT led to significantly greater reductions in PTSD symptom severity and functional impairment compared with placebo. The least squares (LS) mean change in CAPS-5 score was -23.7 (95% CI, -26.94 to -20.44) for MDMA-AT versus -14.8 (95% CI, -18.28 to -11.28) for placebo with therapy (P < 0.001, d = 0.7). The LS mean change in SDS score was -3.3 (95% CI, -4.03 to -2.60) for MDMA-AT versus -2.1 (95% CI, -2.89 to -1.33) for placebo with therapy (P = 0.03, d = 0.4). Severe treatment-emergent adverse events occurred in 5 participants (9.4%) in MDMA-AT versus 2 (3.9%) in placebo; no serious adverse events or deaths occurred.
Why it matters
This confirmatory phase 3 study provides robust evidence that MDMA-assisted psychotherapy reduces PTSD symptom burden and improves daily functioning in a diverse patient population.
Limits
The total sample size was modest (n = 104), and long-term durability of effect was not detailed in the abstract. Additionally, the psychoactive effects of MDMA introduce potential risk of functional unblinding among participants and therapists.
Cited by
- context Clinical trials showed up to 67% PTSD remission or significant reduction from two sessions of MDMA with a qualified therapist in a clinical setting.