Anxiety DisordersPTSDSuicidalityMDMA

Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to paroxetine and sertraline

This review (2019) details the potential superiority of MDMA-assisted psychotherapy as a treatment for PTSD compared to the conventional treatment options paroxetine and sertraline.

Authors

  • Rick Doblin
  • Berra Yazar-Klosinski
  • Michael Mithoefer

Published

Frontiers in Psychiatry
meta Study

Abstract

Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for Psychedelic Studies (MAPS) obtained Breakthrough Therapy Designation (BTD) from the FDA for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD on the basis of pooled analyses showing a large effect size for this treatment. This review covers data supporting BTD. In this treatment, MDMA is administered with psychotherapy in up to three monthly 8-h sessions. Participants are prepared for these sessions beforehand, and process material arising from the sessions in follow-up integrative psychotherapy sessions. Comparing data used for the approval of paroxetine and sertraline and pooled data from Phase 2 studies, MAPS demonstrated that MDMA-assisted psychotherapy constitutes a substantial improvement over available pharmacotherapies in terms of safety and efficacy. Studies of MDMA-assisted psychotherapy had lower dropout rates compared to sertraline and paroxetine trials. As MDMA is only administered under direct observation during a limited number of sessions, there is little chance of diversion, accidental or intentional overdose, or withdrawal symptoms upon discontinuation. BTD status has expedited the development of MAPS phase 3 trials occurring worldwide, leading up to a planned submission seeking FDA approval in 2021.

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Research Summary of 'Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to paroxetine and sertraline'

Introduction

PTSD is a serious, often chronic condition associated with increased mortality, cardio-metabolic disease and suicide risk, and many affected individuals fail to respond to or tolerate available treatments. Two selective serotonin reuptake inhibitors (SSRIs), paroxetine and sertraline, are the only oral medications approved by the FDA for PTSD, but meta-analyses reported only small to moderate effects for pharmacotherapies and substantial dropout rates across trials. Trauma-focused psychotherapies generally demonstrate larger and more durable effects than medications, leaving an unmet need for effective, tolerable treatments for those who do not benefit from first-line options. Feduccia and colleagues set out to summarise the evidence that supported the FDA’s Breakthrough Therapy Designation for MDMA-assisted psychotherapy for PTSD. The review focuses on pooled data from six MAPS-sponsored Phase II trials of MDMA-assisted psychotherapy, and compares efficacy, safety and adherence outcomes from those trials to the pivotal clinical-trial data that supported approval of paroxetine and sertraline. The authors additionally situate MDMA-assisted psychotherapy relative to trauma-focused psychotherapies and describe regulatory developments arising from the Breakthrough designation.

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Study Details

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