Critical review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: Unanswered questions and future directions

Abstract

Background and Aims

Post-Traumatic Stress Disorder (PTSD) is a debilitating condition that affects a sizable proportion of U.S. civilians, military personnel, and veterans. 3,4-Methylenedioxymethamphetamine-Assisted Therapy (MDMA-AT) is a novel treatment approach for PTSD that has both stirred media enthusiasm and drawn criticism. This critical review analyzes individual randomized, controlled trials of MDMA-AT and provides a narrative synthesis.

Methods

A library search and analysis of extant literature reviews was conducted to identify publications containing original research findings with inter-group statistical comparisons from randomized, controlled trials of MDMA-AT. Seven articles were identified. One pilot study was excluded due to a lack of inter-group comparison.

Results

To date, six (four Phase II and two Phase III) randomized, controlled trials of MDMA-AT have been published which met criteria for inclusion in this review. Study design, sponsor, recruitment methods, and participant demographics are similar across trials.

Conclusions

Five out of six reviewed studies provide evidence for the apparent safety and efficacy of MDMA-AT. However, the lack of suitable comparison condition, poor blinding, and rigid study design across trials make interpretation of results difficult. In addition, the high costs of MDMA-AT and lack of head-to-head comparisons with validated PTSD therapies cast doubt on its potential promise as a treatment. The role of the sponsoring organization behind all trials may further introduce bias into findings. Though research to date is encouraging, there is not yet sufficient evidence to suggest that MDMA-AT should be see widespread adoption over current, validated forms PTSD of treatment.