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.Clinical Trial Registration: www.ClinicalTrials.gov, identifiers NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.
Highlights
Breakthrough therapy designation (BTD) is one of the Food and Drug Administration’s (FDA) expedited drug development pathways
We present the evidence included within the breakthrough therapy application showing that MDMA-assisted psychotherapy was superior in phase 2 trials in terms of safety and efficacy compared to the two approved SSRIs for treatment of posttraumatic stress disorder (PTSD)
It is anticipated that MDMA, with its unique pharmacological mechanisms combined with psychotherapy, has advantages over existing medications used as first-line PTSD treatments in terms of safety and side effect profiles, efficacy, and length of remission
Summary
Breakthrough therapy designation (BTD) is one of the Food and Drug Administration’s (FDA) expedited drug development pathways. Data from Phase 2 provides evidence that PTSD, independent of cause, is treatable with 2 to 3 sessions of MDMA-assisted psychotherapy, and offers a larger treatment effect, increased compliance and lower risk of dropout, reduced possibility of drug interactions compared to paroxetine and sertraline. The importance of patient choice regarding therapy for PTSD has been pointed out, and MDMA-assisted psychotherapy may offer advantages in this area if it makes processing trauma less arduous [69] Another recent meta-analysis paper, found no significant differences in benefits of pharmacological, psychotherapeutic, or the combination at the end of treatment, except at the last available endpoint during long-term follow-up, at which point psychotherapeutic treatments were significantly better than medications. Future research could explore whether MDMA combined with existing manualized trauma-focused therapies potentiates PTSD symptom reduction
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