Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials

Psychopharmacology (Berl). 2020 Aug;237(8):2485-2497. doi: 10.1007/s00213-020-05548-2. Epub 2020 Jun 4.

Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual's health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD.

Objectives: To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.

Methods: Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire.

Results: There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = - 44.8 (2.82), p < .0001), with a Cohen's d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = - 5.2 (2.29), p < .05), with a Cohen's d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation.

Conclusions: PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD.

Trial registration: clinicaltrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.

Keywords: Long-term follow-up; MDMA; MDMA-assisted psychotherapy; PTSD.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Retracted Publication

MeSH terms

  • Adult
  • Combined Modality Therapy / methods
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • Psychotherapy / methods*
  • Stress Disorders, Post-Traumatic / diagnosis
  • Stress Disorders, Post-Traumatic / psychology*
  • Stress Disorders, Post-Traumatic / therapy*
  • Surveys and Questionnaires
  • Treatment Outcome

Substances

  • N-Methyl-3,4-methylenedioxyamphetamine

Associated data

  • ClinicalTrials.gov/NCT01211405
  • ClinicalTrials.gov/NCT01958593
  • ClinicalTrials.gov/NCT01793610
  • ClinicalTrials.gov/NCT00353938
  • ClinicalTrials.gov/NCT01689740
  • ClinicalTrials.gov/NCT00090064