MDMA-assisted therapy for major depressive disorder: A seven-month follow-up proof of principle trial

BACKGROUND: Major depressive disorder (MDD) is a leading cause of global disability, and current treatments often fail to provide sustained effectiveness. MDMA-assisted therapy (MDMA-AT) is a promising treatment for MDD. However, the long-term effects are not known. OBJECTIVES: To examine the long-term effects of MDMA-AT for MDD. METHODS: Twelve participants with MDD and an ongoing moderate to severe depressive episode received MDMA-AT in two MDMA dosing sessions one month apart, integrated with nine psychotherapy sessions. Clinical assessments were done before MDMA-AT (baseline), after the final psychotherapy session (post-treatment), and at follow-up seven months after baseline. The primary and secondary outcome measures were the Montgomery-Asberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS), respectively. Suicidality was tracked with the Columbia-Suicide Severity Rating Scale. Exploratory outcomes included self-reported assessments of functional impairment, depression, generalized anxiety, insomnia, and PTSD symptoms. We used a mixed-effects model and multinomial logistic regression for analysis of repeated measures. RESULTS: All twelve participants attended the follow-up visit. At follow-up, there was a significant reduction of MADRS (p < 0.001) and SDS (p = 0.001) scores compared with baseline, along with significant improvements in all exploratory outcome measures. There were no significant changes in any measures from the post-treatment visit. Neither the mean suicidal ideation (SI) score nor the SI intensity rating exceeded pre-study levels. CONCLUSION: This long-term follow-up study of MDMA-AT provides preliminary evidence supporting sustained treatment effects and long-term safety in MDD. However, further validation in larger, controlled trials is needed. CLINICAL TRIAL IDENTIFICATION: EudraCT number 2021-000805-26.