MDMA-assisted therapy for major depressive disorder: A seven-month follow-up proof of principle trial
In this paper, which is a long-term follow-up (n=12) of participants with moderate-to-severe major depressive disorder who received MDMA-assisted therapy (two dosing sessions integrated with nine psychotherapy sessions) found significant reductions in depression severity and functional impairment at seven months compared to baseline, with improvements maintained from the post-treatment assessment and no increases in suicidal ideation.
“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.”
Kvam TM, Goksøyr IW, Rog J, van de Vooren IJ, Stewart LH, Autran I, Berthold-Losleben M, Mørch-Johnsen L, Holst R, Røssberg JI, Clausen I, Andreassen OA. MDMA-assisted therapy for major depressive disorder: A seven-month follow-up proof of principle trial. J Psychiatr Res. 2025 Nov 27;193:302-308. Link to Paper
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