This 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.
Abstract of MDMA-Assisted Therapy for Major Depressive Disorder Follow-Up
“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.”
Authors: Tor-Morten Kvam, Ivar W. Goksøyr, Justyna Rog, Inger-Tove Jentoft van de Vooren, Lowan Han Stewart, Ingrid Autran, Mark Berthold-Losleben, Lynn Mørch-Johnsen, René Holst, Jan Ivar Røssberg, Ingmar Clausen & Ole A. Andreassen
Summary of MDMA-Assisted Therapy for Major Depressive Disorder Follow-Up
Kvam and colleagues situate the study within the broader public health burden of major depressive disorder (MDD), describing it as a common, recurrent, and disabling condition affecting an estimated hundreds of millions of people worldwide. They note that both antidepressant medication and psychotherapy are established treatments, and that combining the two is often recommended. However, earlier research shows substantial limitations: around 30% of people do not respond to at least two sequential antidepressants, and even with psychotherapy, only about one third achieve full remission while many either drop out or relapse within a few years. Long-term maintenance with antidepressants can help but carries side-effects and does not guarantee sustained wellness. Against that backdrop, the authors argue that there is a pressing need for novel treatments that are both well tolerated and capable of producing long-lasting benefit.
The introduction then shifts to 3,4-methylenedioxymethamphetamine (MDMA), described as a stimulant with both monoamine-releasing and reuptake-inhibiting properties, particularly increasing serotonin levels in the brain. The authors stress that MDMA’s effects are highly context-dependent, differing markedly between recreational settings and controlled clinical environments. In MDMA-assisted therapy (MDMA-AT), the compound is combined with a structured psychotherapeutic programme. The subjective effects of MDMA—such as increased self-compassion and enhanced emotional processing—are thought to support psychotherapy by helping people engage with difficult material in a more open and regulated way. MDMA-AT typically involves two or three extended dosing sessions, each lasting about eight hours, embedded within a broader series of preparatory and integration therapy sessions.
The psychotherapeutic approach is described as inner-directed and participant-centred, emphasising trust in the process, non-directive support, and the idea of an “inner-healing intelligence”, meaning an innate capacity of the individual to move towards recovery if given the right conditions. This idea has been explored in other psychedelic trials and is presented here as one possible mechanism for sustained change beyond the acute drug effects. Prior MDMA-AT studies in post-traumatic stress disorder (PTSD) have shown not only short-term efficacy but also sustained improvements and even further gains at long-term follow-up in pooled Phase II data. On that basis, the authors set out their aim: to examine whether MDMA-AT can produce sustained benefits and maintain safety in people with MDD, by assessing outcomes seven months after baseline (approximately six months after the last MDMA session and four months after the end of the trial treatment).
Methods
Study design and participants
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