Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials
Pooled analysis of six phase 2 trials found that two to three MDMA‑assisted psychotherapy sessions produced large reductions in PTSD severity at 1–2 months (LS mean change −44.8; Cohen’s d = 1.58) with further small but significant improvement at least 12 months post‑treatment (LS mean change −5.2; d = 0.23). The proportion no longer meeting PTSD criteria rose from 56% at treatment exit to 67% at long‑term follow‑up, most participants reported lasting benefits (improved relationships and well‑being) and only a minority reported harms; phase 3 trials are underway to confirm these results.
Authors
- Rick Doblin
- Berra Yazar-Klosinski
- Michael Mithoefer
Published
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
Research Summary of 'Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials'
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Introduction
PTSD is a chronic disorder with substantial prevalence in the general population and markedly higher rates among certain groups such as military veterans and first responders. Existing pharmacological and psychotherapeutic treatments can be effective but many patients either do not respond, discontinue treatment, or relapse; trauma-focused psychotherapies generally produce more durable benefits than medications but a substantial treatment‑resistant population remains. MDMA-assisted psychotherapy, a drug-assisted therapy that pairs MDMA administration with a structured course of psychotherapy that attends to set and setting, was designated a Breakthrough Therapy by the FDA in 2017 on the basis of preliminary phase 2 findings and is hypothesised to work by altering emotional memory processing, increasing self-compassion and empathy, and facilitating fear extinction in a therapeutic context. Jerome and colleagues set out to examine longer-term outcomes after MDMA-assisted psychotherapy by pooling long-term follow-up (LTFU) data from six Phase II trials. The primary aim was to evaluate change in PTSD symptom severity (measured with the Clinician-Administered PTSD Scale for DSM‑IV, CAPS‑IV) from baseline through treatment exit and at least 12 months after the final MDMA session, and to summarise participant-reported benefits and harms using a long-term follow-up questionnaire (LTFUQ). The pooled approach was intended to increase sample size and provide information to inform Phase III assessment planning.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., ... & Doblin, R. (2020). RETRACTED ARTICLE: Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology, 237(8), 2485-2497.
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