FDA Advisory Panel Declines to Recommend MDMA for PTSD Treatment

WASHINGTON — On Tuesday, a Food and Drug Administration (FDA) advisory panel declined to recommend the approval of MDMA, commonly known as ecstasy or molly, as a treatment for post-traumatic stress disorder (PTSD). This decision represents a significant setback for advocates who have long pushed for the inclusion of psychedelics in treating mental health disorders.

Panel Decision and Concerns

The two votes — one for the treatment’s efficacy and one for its safety — were cast by the agency’s Psychopharmacologic Drugs Advisory Committee. This marked the first time FDA advisers considered a Schedule I psychedelic for medical use. If approved, MDMA would have been the first new treatment for PTSD in over two decades.

Panel members struggled to balance the urgent need for new PTSD treatments against serious concerns about the data submitted by drugmaker Lykos Pharmaceuticals. Issues cited included inconsistencies, poor study design, and allegations of misconduct.

“It sounds like MDMA has really impacted a number of people in positive ways, but it seems that there are so many problems with the data,” said Melissa Decker Barone, an adjunct assistant professor in the department of psychiatry at the University of Maryland School of Medicine.

Dr. Walter Dunn, an assistant clinical professor in the department of psychiatry at the University of California Los Angeles, was the sole “yes” vote on safety and one of two "yes" votes on efficacy. While he acknowledged concerns about the drug, he emphasized the dire need for PTSD treatments. “There’s no free lunch in medicine,” Dunn said. “What has the potential for benefit has the potential for harm.”

Clinical Trials and Data Concerns

The panel's decision was based on the results of two Phase 3 clinical trials involving nearly 200 patients with moderate to severe PTSD. In both trials, a treatment approach combining MDMA with talk therapy sessions proved more effective than a placebo in reducing symptom severity. In the most recent trial, published in September, about 86% of participants who received MDMA and talk therapy saw a reduction in symptom severity after 18 weeks, compared to about 71% of participants who received the placebo and therapy.

However, an FDA analysis published last week raised concerns about the trials' methodology. Due to the profound effects of MDMA, the vast majority of participants could accurately guess whether they had received the drug or a placebo, potentially inflating the results. “We expressed continued concern about the adequacy of blinding,” said Dr. David Millis, an FDA official overseeing Lykos' application.

Broader Concerns and Allegations

The Institute for Clinical and Economic Review, a nonprofit group evaluating drug costs, noted that trial participants treated psychedelics “more like a religious movement than like pharmaceutical products.” Panel members were troubled by reports that many patients had prior MDMA use and that some therapists might have encouraged favorable reports from patients.

“The data was promising, but given the 40% of people who had previously used MDMA, limited information about recruitment and recruitment coming through referrals — I really wonder how much that impacted the efficacy,” said Elizabeth Joniak-Grant, a patient representative and sociologist at the University of North Carolina, Chapel Hill.

Serious concerns also arose about potential risks to patients from providers, following allegations of sexual misconduct during an earlier trial. Lykos recommended that two therapists be present during therapy sessions, but panel members insisted both therapists be licensed and that patient concerns be addressed with a clear reporting pathway.

“We need a clear pathway for reporting,” said Kim Witczak, a consumer representative and the executive director of Woody Matters, a drug safety organization. “I’ve been around drug safety issues for a long time, and I hear from harmed patients all the time. The reality is patients report, but nothing gets done.”

Next Steps and Broader Impact

The decision now goes to the FDA, which is expected to make a final ruling by August 11. While the committee’s vote is only a recommendation, the FDA typically follows its advice.

Approximately 13 million people in the U.S., including many veterans, suffer from PTSD, which can cause debilitating symptoms such as intrusive memories, nightmares, anxiety, suicidal thoughts, and trouble sleeping. Current treatments include talk therapy and two antidepressants, sertraline (Zoloft) and paroxetine (Paxil), though many patients drop out of therapy and response rates to medication are often low.

Researchers continue to explore how MDMA might aid PTSD patients, with some suggesting the drug may help by reducing fear and anxiety responses in the brain.

Conclusion

The FDA advisory panel's decision to decline recommending MDMA for PTSD treatment underscores the complexities and challenges in approving new treatments for mental health disorders. While the potential benefits of MDMA are recognized, the concerns about data integrity and patient safety have highlighted the need for rigorous standards in clinical research. The final decision by the FDA will be closely watched, as it holds significant implications for the future of psychedelic-assisted therapies in mental health treatment.

The panel's vote reflects a cautious approach to introducing new treatments, emphasizing the importance of robust, reliable data in ensuring patient safety and treatment efficacy. The outcome of this decision will likely influence future research and development in the field of psychedelic medicine, potentially shaping the landscape of mental health treatment for years to come.