Pooled data from six phase 2 randomized controlled trials support the use of MDMA plus psychotherapy for the treatment of PTSD.
In 2017, the FDA granted breakthrough therapy designation to MDMA-assisted psychotherapy for PTSD and approved the designs of two phase 3 trials that began in 2018.
In this article published in Psychopharmacology, Michael C. Mithoefer, MD, from the department of psychiatry and behavioral sciences at the Medical University of South Carolina, and colleagues presented a pooled analysis of the six phase 2 trials to optimize the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.
The six randomized, double-blind, controlled clinical trials were conducted at five study sites between April 2004 to February 2017. During manualized psychotherapy sessions, 72 adults with PTSD received active doses of MDMA (75 mg to 125 mg) and 31 received placebo/control doses (0 mg to 40 mg) in two or three 8-hour sessions spaced 1 month apart. Before the first MDMA exposure, participants received three nondrug 90-minute therapy sessions as well as three to four after each experimental session.
Along with safety outcomes, the researchers measured patients’ change in Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV; primary outcome) and the Beck Depression Inventory—II (BDI-II; secondary outcome).
After two blinded experimental sessions, the results showed that those receiving MDMA-assisted psychotherapy had significantly greater decrease in CAPS-IV total scores from baseline than those in the control group (estimated mean difference between groups 22; P<.001).
Based on CAPS-IV assessment 1 to 2 months after the two experimental sessions, the investigators found that more participants in the active group (54.2%) did not meet PTSD diagnostic criteria than the control group (22.6%). Furthermore, depression symptom improvement (based on the BDI-II) was greater for the active-dose group than the control group (estimated mean change =–12.4 vs. –6.5).
All MDMA doses were well tolerated and there were no adverse events or treatment
discontinuation relating to “ecstasy” seeking or craving, according to the findings. In the week following experimental sessions, some reactions occurred more often in the active dose group for the first few days, but declined by the end of the week. In addition, the researchers observed no unexpected MDMA-related serious adverse events.
“Based on the promising safety and efficacy results from these six phase 2 trials, we have designed multi-site, placebo-controlled phase 3 trials that started in late 2018 to evaluate MDMA-assisted psychotherapy in approximately 200 participants with PTSD. ... if findings are significant and no new safety concerns arise, MDMA could become an FDA-approved treatment for PTSD in the context of psychotherapy by 2021,” Mithoefer and colleagues wrote. – by Savannah Demko
Disclosure: Mithoefer reports salary from the Multidisciplinary Association for Psychedelic Studies Public Benefit Corporation. Please see the study for all other authors’ relevant financial disclosures.