3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy is effective in treating post-traumatic stress disorder (PTSD) in military veterans, firefighters, and police officers, according to the results of a randomized, double-blind, dose-response, phase 2 clinical trial published in The Lancet Psychiatry.
PTSD affects 17.1% of military veterans and 10% to 32% of first responders. Effectiveness of therapies such as sertraline and paroxetine has been limited, particularly in veterans. Use of antidepressants, antipsychotics, mood stabilizers, and benzodiazepines is off-label but common, although evidence for these therapies is lacking.
Michael C. Mithoefer, MD, from the Department of Psychiatry and behavioral sciences at the Medical University of South Carolina in Charleston, and colleagues performed a randomized double-blind dose-response phase 2 trial at an outpatient psychiatric clinic. The study included service personnel who were 18 or older, had chronic PTSD of at least 6 months duration, and had a Clinician-Administered PTSD Scale (CAPS-IV) total score of ≥50.
The investigators randomly assigned participants to 3 different MDMA dose groups plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. MDMA was administered orally in two 8-hour sessions along with concomitant psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second session. This initial trial period was followed by an open-label crossover phase in which patients who had received 30 mg and 75 mg underwent three 100- to 125-mg MDMA-assisted psychotherapy sessions. All participants were then assessed 12 months after the final MDMA session.
The 26 veterans and first responders had a mean baseline CAPS-IV total score of 87.1. The 75-mg and 125-mg groups had significantly greater reductions in PTSD symptom severity, with a mean change in CAPS-IV total scores of −58.3 and −44.3 (P =.001), compared with individuals in the 30-mg group (-11.4). During the open-label crossover phase with full-dose MDMA, PTSD symptom severity decreased significantly in the group that had been receiving 30 mg MDMA; however, no further decreases were noted in individuals who had previously received 75 mg MDMA and achieved a strong response. At the 12-month follow-up, PTSD symptoms continued to be significantly reduced compared with baseline in all groups, with a mean CAPS-IV total score of 38.8 (P <.0001). In total, 85 adverse events were reported during the trial by 20 participants; 4 were serious, but only 1 was deemed possibly related to treatment with MDMA.
The investigators contend that this trial provides further evidence that MDMA-assisted psychotherapy is safe and effective for treating patients with chronic PTSD. As a result of 6 phase 2 trials, the FDA has designated MDMA-assisted psychotherapy for PTSD as breakthrough therapy.
Disclosures: MCM has received research funds from the Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation as a clinical investigator and clinical trial medical monitor, as well as for training and supervision of research psychotherapists. ATM has received research funds from MAPS Public Benefit Corporation as a clinical investigator and for training and supervision of research psychotherapists. AAF, LJ, and AE are full-time employees of MAPS Public Benefit Corporation. MW and JW have received research funds to do study assessments. JH declares no competing interests. SH has received research funds from MAPS Public Benefit Corporation for his role as a biostatistician. BY-K and RD are full-time employees of MAPS.
Mithoefer MC, Mithoefer AT, Feduccia AA, et al. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial [published online May 1, 2018]. Lancet Psychiatry. doi:10.1016/S2215.0366(18)30125-4