Results from a phase 2 study showed that supervised administration of 3,4-methylenedioxymethamphetamine, known as MDMA, delivered in a controlled setting with adjunctive psychotherapy was well-tolerated and effective in reducing PTSD symptoms in veterans and first responders.
“Off-label prescription of drugs, including antidepressants, antipsychotics, mood stabilizers and benzodiazepines, is common, although risks and benefits for PTSD have not been established in randomized controlled trials,” Michael C. Mithoefer, MD, department of psychiatry and behavioral sciences Medical University of South Carolina, Charleston, and colleagues wrote. “Development of new treatments should address the common reasons for treatment avoidance, failure and dropout.”
The investigators conducted a randomized, double-blind, dose-response trial at a U.S. outpatient psychiatric clinic to examine the efficacy and safety of MDMA-assisted psychotherapy for the treatment of chronic PTSD in military personnel and first responders.
Participants were randomly allocated (1:1:2) to one of three dose groups to receive MDMA— 30 mg (active control), 75 mg or 125 mg — administered orally in two 8-hour sessions. Patients also received concomitant psychotherapy. Subsequently, those in the 30-mg and 75-mg groups underwent three 100-mg to 125-mg MDMA-assisted psychotherapy sessions in an open-label crossover with full-dose MDMA. All participants were examined 1 year after the last MDMA session.
Supervised administration of MDMA delivered in a controlled setting with adjunctive psychotherapy was well-tolerated and effective in reducing PTSD symptoms in veterans and first responder, according to results from a phase 2 study.
Researchers examined mean change in Clinician-Administered PTSD Scale (CAPS-IV) total score from baseline to 1 month after the second experimental session. They monitored safety through adverse events, spontaneously-reported expected reactions, vital signs and suicidality.
In total, 26 veterans and first responders were randomly assigned to receive 30 mg (n = 7), 75 mg (n = 7) or 125 mg (n = 12) of MDMA along with psychotherapy. One month after the second experimental session, participants who received 75 mg and 125 mg of MDMA-assisted psychotherapy experienced greater decreases in PTSD symptom severity (mean change CAPS-IV total scores = –58.3 and –44·3; P = .001) compared with those in the 30-mg group (–11.4). More participants in high-dose groups no longer met diagnostic criteria for PTSD than those in the low-dose group (58% in the 125-mg group and 86% in the 75-mg group vs. 29% in the 30-mg group), according to the press release.
In the open-label crossover, Mithoefer and colleagues found the group that previously received MDMA 30 mg experienced a significant drop in PTSD symptom severity scores; however, this was not observed in the group that previously saw a large response after receiving the 75-mg dose.
Moreover, at the 12-month follow-up, patients saw reductions in PTSD symptoms compared with baseline after all groups received full-dose MDMA (P < .0001). Overall, participants reported four serious adverse events, only one of which was possibly related to study drug treatment.
“Promising phase 2 efficacy and safety results have now been shown in six studies. This trial provides further evidence that MDMA-assisted psychotherapy can be used safely and effectively for treating patients with chronic PTSD,” the authors wrote. “If findings are validated in [Multidisciplinary Association for Psychedelic Study’s] phase 3 clinical trials, set to start in 2018, MDMA-assisted psychotherapy might become a viable, FDA-approved treatment option for PTSD by 2021.”
Mithoefer and colleagues show that — with careful medical and psychological supervision — short-term use of MDMA in this specific population appears safe, Andrea Cipriani, MD, PhD, and Philip J. Cowen, MD, from the department of psychiatry, University of Oxford, and Oxford Health NHS Foundation Trust, wrote in a related commentary.
“The generalizability of the benefit of MDMA-assisted psychotherapy to more mainstream psychiatry remains to be established,” Cipriani and Cowen wrote. – by Savannah Demko
Disclosures: Mithoefer reports research funds from the Multidisciplinary Association for Psychedelic Studies (MAPS) Public Benefit Corporation. Please see the full study for other authors’ relevant financial disclosures. Cipriani and Cowen report no relevant financial disclosures.