FDA panel rejects first MDMA treatment amid deep concerns about flawed trials

A Food and Drug Administration advisory panel on Tuesday declined to recommend the approval of MDMA, commonly known as ecstasy or molly, as a treatment for post-traumatic stress disorder, a major setback for advocates who have long pushed to include psychedelics in treating mental health disorders.

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

The votes reflected panel members’ struggle to balance the need for new PTSD treatments against serious concerns about the data submitted by drugmaker Lykos Pharmaceuticals, which they say was marred by 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 had concerns about the drug, he noted that “we are in dire need of treatments for PTSD.”

“There’s no free lunch in medicine,” Dunn said. “What has the potential for benefit has the potential for harm.”

The panel’s decision was based on the results of two Phase 3 clinical trials that included nearly 200 patients with moderate to severe PTSD. In both trials, researchers found that a treatment approach that consisted of MDMA given in three eight-hour therapy sessions, four weeks apart, worked better than a placebo in reducing the severity of their symptoms. People also had a number of shorter talk therapy sessions before and after getting the drug or the placebo.

In the most recent trial, published last September, about 86% of participants who got the MDMA treatment along with talk therapy saw a reduction in the severity of their symptoms after 18 weeks. About 71% of participants who got the treatment met the diagnostic criteria for PTSD, compared to about 48% who also got therapy but took a placebo instead.

The vote came after an analysis from FDA scientists, published last week, raised concerns about how the trials were carried out.

A double-blinded, randomized clinical trial is considered the gold standard for determining whether a drug works better than a placebo. “Double-blinded” means that neither the patient nor the researcher administering the drug knows whether it is a placebo or the real thing.

In the MDMA trials, however, due to the “profound alterations in mood, sensation, suggestibility and cognition,” the vast majority of the participants were able to accurately guess which treatment they had received after the study ended, the FDA scientists wrote. “As a result, studies are nearly impossible to blind.”

This could “artificially inflate” the results, Dr. David Millis, an FDA official who oversaw Lykos' approval application, said during Tuesday’s meeting, because participants may feel the treatment is working if they know they are on the drug, or conversely not working if they are on a placebo.

“We expressed continued concern about the adequacy of blinding,” he said.

Last week, the Institute for Clinical and Economic Review, a nonprofit group that evaluates the cost of drugs, said patients and providers in the trial treated psychedelics “more like a religious movement than like pharmaceutical products.”

Indeed, panel members had reservations about the trials, including that many patients had used MDMA before and that some therapists may 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.

Panel members also expressed serious concerns about potential risks to patients at the hands of providers, following allegations of sexual misconduct during an earlier trial.

Lykos recommended that two therapists be present for the therapy sessions. Panel members wanted to ensure that both therapists were licensed, and that patient concerns would be addressed.

“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 and the reality is patients report, nothing gets done.”??

The decision will now go to the FDA, which is expected to make a final ruling by Aug. 11. The committee’s vote is only a recommendation and the agency doesn’t have to follow its advice, although it usually does.

About 13 million people in the U.S., many of whom are veterans, have PTSD, according to the FDA. The condition, which develops in some people exposed to serious injury or violence, can be debilitating: People often experience intrusive memories and nightmares that can cause high levels of anxiety, suicidal thoughts, self-destructive behavior and trouble sleeping.

Talk therapy is the first line of treatment for the condition, either alone or in combination with one of two antidepressants, sertraline (Zoloft) or paroxetine (Paxil). However, data presented by the agency at Tuesday’s meeting found patients often drop out with talk therapy alone. What’s more, response rates to the medications rarely exceed 60% and less than 20% to 30% of patients with PTSD achieve full remission of their symptoms.

Researchers are still trying to understand exactly how MDMA helps people with PTSD, but the drug is thought to work in part by quieting the fear and anxiety response in the brain, said David Olson, director of the U.C. Davis Institute for Psychedelics and Neurotherapeutics.

This article was originally published on NBCNews.com