Adding 3,4-methylenedioxymethamphetamine (MDMA) to integrative psychotherapy may significantly improve symptoms and well-being for patients with severe posttraumatic stress disorder, including those with the dissociative subtype, new research suggests.
MAPP1 is the first phase 3 randomized controlled trial of MDMA-assisted therapy in this population. Participants who received the active treatment showed greater improvement in PTSD symptoms, mood, and empathy in comparison with participants who received placebo.
MDMA was “extremely effective, particularly for a subpopulation that ordinarily does not respond well to conventional treatment,” study coinvestigator Bessel van der Kolk, MD, professor of psychiatry at Boston University School of Medicine, told delegates attending the virtual European Psychiatric Association (EPA) 2021 Congress.
Growing interest
, particularly because failure rates with most available evidence-based treatments have been relatively high.
As previously reported by this news organization, in 2017, the U.S. Food and Drug Administration approved the trial design of Dr. van der Kolk’s and colleagues’ MAPP1 study after granting MDMA breakthrough designation.
The MAPP1 investigators assessed 90 patients with PTSD (mean age, 41 years; 77% White; 66% women) from 50 sites. For the majority of patients (84%), trauma history was developmental. “In other words, trauma [occurred] very early in life, usually at the hands of their own caregivers,” Dr. van der Kolk noted.
In addition, 18% of the patients were veterans, and 12% had combat exposure. The average duration of PTSD before enrollment was 18 years. All patients underwent screening and three preparatory psychotherapy sessions at enrollment.
Participants were randomly assigned to receive MDMA 80 mg or 120 mg (n = 46) or placebo (n = 44) followed by three integrative psychotherapy sessions lasting a total of 8 hours. A supplemental dose of 40 or 60 mg of MDMA could be administered from 1.5 to 2 hours after the first dose.
The patients stayed in the laboratory on the evening of the treatment session and attended a debriefing the next morning. The session was repeated a month later and again a month after that. In between, patients had telephone contact with the raters, who were blinded to the treatment received.
Follow-up assessments were conducted 2 months after the third treatment session and again at 12 months. The primary outcome measure was change in Clinician Administered PTSD Scale for DSM 5 (CAPS-5) score from baseline.
‘Dramatic improvement’
Results showed that both the MDMA and placebo groups experienced a statistically significant improvement in PTSD symptoms, “but MDMA had a dramatically significant improvement, with an effect size of over 0.9,” Dr. van der Kolk said.
The MDMA group also reported enhanced mood and well-being, increased responsiveness to emotional and sensory stimuli, a greater sense of closeness to other people, and a greater feeling of empathy.
Patients also reported having heightened openness, “and clearly the issue of empathy for themselves and others was a very large part of the process,” said Dr. van der Kolk.
“But for me, the most interesting part of the study is that the Adverse Childhood Experiences scale had no effect,” he noted. In other words, “the amount of childhood adverse experiences did not predict outcomes, which was very surprising because usually those patients are very treatment resistant.”
Dr. van der Kolk added that the dissociative subtype of PTSD was first described in the DSM-5 and that patients are “notoriously unresponsive to most unconventional treatments.”
In the current study, 13 patients met the criteria for the subtype, and investigators found they “did better than people with classical PTSD,” Dr. van der Kolk said. He added that this is a “very, very important finding.”