Trial PaperPTSDSafety & Risk ManagementMDMAPlacebo

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial

This multi-site, randomised, double-blind, Phase IIIb trial (n=104) evaluated the efficacy and safety of MDMA-assisted therapy (MDMA-AT) for individuals with moderate to severe PTSD. The study found significant reductions in PTSD severity (CAPS-5 score) and functional impairment (SDS score) for the MDMA-AT group compared to placebo with therapy. Seven participants experienced severe treatment-emergent adverse events, but no deaths or serious adverse events were reported. The treatment was found to be generally well tolerated in a diverse population.

Authors

  • Michael Mithoefer
  • Rick Doblin
  • Berra Yazar-Klosinski

Published

Nature Medicine
individual Study

Abstract

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was −23.7 (−26.94, −20.44) for MDMA-AT versus −14.8 (−18.28, −11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was −3.3 (−4.03, −2.60) for MDMA-AT versus −2.1 (−2.89, −1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated.

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Research Summary of 'MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial'

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Brief significance note, e.g. around this being the first Phase IIb study on this etc

Introduction

Post-traumatic stress disorder (PTSD) is a disabling condition with substantial individual and societal burden; many patients have persistent symptoms and poor responses to existing treatments, including selective serotonin reuptake inhibitors (SSRIs). Earlier trials and mechanistic work suggested that 3,4-methylenedioxy­methamphetamine-assisted therapy (MDMA-AT) may enhance psychotherapeutic engagement and facilitate fear extinction and memory reconsolidation, but confirmatory data in a diverse sample with moderate to severe PTSD were limited. Mitchell and colleagues conducted MAPP2, a multi-site, randomized, double-blind, placebo-controlled Phase III trial, to test whether MDMA-AT reduces clinician-rated PTSD symptom severity and improves functional impairment compared with placebo plus identical therapy. The trial aimed to extend findings from an earlier Phase III study (MAPP1) into an ethnoracially diverse population with longstanding moderate to severe PTSD and several comorbidities.

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Study Details

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References (13)

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MDMA-assisted therapy for moderate to severe... — Research Summary & Context | Blossom