Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials

MDMA-assisted psychotherapy showed a very large effect (d=1.58, 56% no longer met PTSD criteria) which improved at 12-months follow-up (d=0.43, 67%).

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.”

Authors: Lisa Jerome, Allison A. Feduccia, Julie B. Wang, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson, Michael C. Mithoefer & Rick Doblin

Notes

This paper is included in our ‘Top 10 Articles on Psychedelics in the Year 2020

“The present analysis extends the follow-up of participants across six phase 2 clinical trials who had participated in a treatment protocol consisting of two or three 8-h psychotherapy sessions combined with MDMA for treatment of PTSD.”

The studies were similar in design and the data of them was combined to get 107 participants, 74 of which were in the active (MDMA) group. At the endpoint 91 completed the follow-up, of which 83 also the questionnaire.

“Compared to baseline, 82.0% of participants achieved a clinically significant drop of 15 points or greater in CAPS-IV total scores [PTSD structured interview/measure] at treatment exit, and 26.4% had a 15-point or greater decrease from treatment exit to LTFU [long term follow-up]. There were 11 (12.1%) participants who experienced a relapse, defined as a 15-point or greater drop in CAPS-IV scores at treatment exit but then a 15-point or greater increase in scores from treatment exit to LTFU.”

“At 12-month follow-up, 97.6% of participants across studies reported experiencing benefits, and among the participants who reported benefits, 92.2% reported that some to all benefits lasted with 53.2% indicating large benefits that lasted or continued to grow.”

These results are phenomenal. Of the participants that experienced harm (8.4%) the most identified cause was worsened mood. Of those (9 participants) that relapsed, all had one or more significantly stressful event.

“At LTFU, 8 of 83 participants (9.6%) reported having used Ecstasy or MDMA between treatment exit and long-term follow-up.”

Only two of those hadn’t used it before and all were using it therapeutically or recreationally.

“The pharmacologic effects of MDMA administered within a course of psychotherapy engender a unique therapeutic process that seems to enhance treatment engagement, reduce treatment discontinuation, and extend treatment effects.”

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