MDMA for PTSD: Notes on the Phase 3 Study Published This Week
On Monday, MAPS’ Phase 3 study of MDMA-assisted therapy for severe PTSD was published in Nature Medicine. As we reported in last week’s bulletin, the results are impressive. Or, as our Pharmaceutical Advisor Michael Haichin put it: “Both the efficacy and safety results are pretty astounding.” The additional notes below are adapted from a Twitter thread Michael shared.
No Obvious Impact of Past SSRI Usage
Importantly, the study found that there was “no obvious impact of SSRI history on the effectiveness of MDMA.” This is a reassuring finding, especially in the context of a study published last year that suggested past antidepressant usage reduces the efficacy of MDMA-assisted psychotherapy for PTSD (Note: Michael authored an informative article for Psychedelic Science Review which covered the study in question). It’s not clear why we see a discrepancy between these findings, but we may expect deeper analysis following the second Phase 3 trial, which is currently enrolling.
Diversity and Representation
We still have a significant amount of work to do in terms of representation in clinical trials of psychedelics. Just 2 participants were black or African American, representing just over 2% of the sample size. For context, according to the US Census Bureau around 13.4% of the U.S. population is black or African American.
A significant body of literature (e.g., Roberts et al., 2010) shows that lifetime prevalence of PTSD is higher in minority groups than Whites, but that minority groups are less likely to seek treatment. While, like many clinical trials, MAPS’ study falls short of representing society in an equitable manner, it is hoped that MAPS will be in a position to deliver MDMA-Assisted Therapy to a diverse range of individuals, should it be approved. MAPS team members like Ismail L. Ali are leading the way in this regard.
Overnight Stay vs. Evening Discharge
The study also found that whether or not a participant had an overnight stay following treatment had no effect on the success of the protocol. This was achieved by allowing participants at two study sites to be discharged in the evening, as opposed to being kept at the site overnight.
Haichin points out that the ability to eliminate the overnight stay from the treatment protocol would have significant impacts on cost-effectiveness. However, he also points out that 10/14 participants that requested further integrative visits were in the MDMA arm, indicating that the amount of psychotherapy in the current model may be insufficient for some.
The Blinding Problem
As with most, if not all, psychedelic studies, the elephant in the room is the ability of the researchers to adequately prevent participants from guessing what treatment they received, and potentially influencing the results. Previous MDMA research used low-dose MDMA instead of an inactive placebo in the comparator group, which improved blinding but made participants’ PTSD worse. Since the use of low-dose MDMA made it easier to find a treatment difference (and would be unethical to give), MAPS decided—in partnership with the FDA—that an inactive placebo group was more appropriate for both Phase III trials.
“However, although blinding was not formally assessed during the study, when participants were contacted to be informed of their treatment assignment at the time of study unblinding it became apparent that at least 10% had inaccurately guessed their treatment arm. Although anecdotal, at least 7 of 44 participants in the placebo group (15.9%) inaccurately believed that they received MDMA, and at least 2 of 4 participants in the MDMA group (4.3%) inaccurately believed that they had received placebo.”
In other words, almost 90% of participants guessed whether they received MDMA-assisted psychotherapy or not. Because of this, critics will say the trial is essentially open-label, where the given treatment is known and treatment effects tend to be overestimated.
Follow Michael Haichin on Twitter for regular updates.
Notable Coverage of the Study
The New York Times: The Psychedelic Revolution Is Coming. Psychiatry May Never Be the Same.
BBC: MDMA could help trauma survivors face painful memories
Time: A New Study Points to MDMA as a Powerful Treatment for PTSD
Fast Company: Psychedelic medicine is about to blow up