A Food and Drug Administration advisory committee declined Tuesday to recommend 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 the treatment of mental health. troubles.
The two votes — one for the treatment’s effectiveness and one for its safety, by the agency’s Psychopharmacologic Drugs Advisory Committee — marked the first time FDA advisers considered a Schedule I psychedelic for use medical. If approved, it would have been the first new treatment for PTSD in more than two decades.
The votes reflect panel members’ struggle to balance the need for new treatments for PTSD and serious concerns about data submitted by drugmaker Lykos Pharmaceuticals, which they said was marred by inconsistencies, poor design studies and allegations of misconduct.
“It appears that MDMA has had a positive impact on a number of people, but it appears that there are many problems with the data,” said Melissa Decker Barone, an adjunct assistant professor in the department of psychiatry at the school at the University of Maryland. of Medicine.
Dr. Walter Dunn, an assistant clinical professor in the department of psychiatry at the University of California, Los Angeles, was the only “yes” vote on safety and one of two “yes” votes on effectiveness. Although he had concerns about the drug, he emphasized that “we desperately need treatments for PTSD.”
“There is no free lunch in medicine,” Dunn said. “What has the potential for good has the potential for harm. »
The committee’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, researchers found that a treatment approach of administering MDMA in three eight-hour therapy sessions, four weeks apart, was more effective than a placebo in reducing the severity of their symptoms. . People also underwent a number of shorter talk therapy sessions before and after receiving the drug or placebo.
In the most recent trial, published last September, about 86% of participants who received MDMA treatment combined with talk therapy saw a reduction in the severity of their symptoms after 18 weeks. About 71% of participants who received the treatment met diagnostic criteria for PTSD, compared to about 48% who also received treatment but took a placebo instead.
The vote came after an analysis by FDA scientists, released last week, raised concerns about how the trials were conducted.
A double-blind, randomized clinical trial is considered the gold standard for determining whether a drug works better than a placebo. “Double-blind” means that neither the patient nor the researcher administering the drug knows whether it is a placebo or the actual drug.
However, in the MDMA trials, due to the “profound alterations in mood, sensations, suggestibility, and cognition”, the vast majority of participants were able to accurately guess what treatment they received after the end of the study, the FDA scientists wrote. “As a result, studies are almost impossible to blind.”
This could “artificially inflate” the results, Dr. David Millis, an FDA official who oversaw Lykos’s approval bid, said at Tuesday’s meeting, because participants may be left with the impression that the treatment works if they know they are taking the medicine, or conversely, it does not work. if they take a placebo.
“We have expressed our continued concern about the adequacy of blinding,” he said.
Last week, the Institute for Clinical and Economic Review, a nonprofit group that estimates drug costs, said patients and providers in the trial treated psychedelics “more like a religious movement than pharmaceutical products “.
Indeed, panel members had reservations about the trials, including that many patients had already used MDMA and that some therapists might have encouraged favorable reports from patients.
“The data was promising, but given that 40% of people had previously used MDMA and there was limited information on recruitment and recruitment from referrals, I really wonder how much of an impact this had on the “effectiveness,” said patient representative Elizabeth Joniak-Grant. and sociologist at the University of North Carolina, Chapel Hill.
Panel members also expressed serious concerns about potential risks to patients from providers, following allegations of sexual misconduct in an earlier trial.
Lykos recommended that two therapists be present for therapy sessions. Committee members wanted to ensure that both therapists were licensed and that patients’ concerns would be addressed.
“We need a clear path to reporting,” said Kim Witczak, a consumer representative and executive director of Woody Matters, a drug safety organization. “I have been interested in medication safety issues for a long time and I constantly hear from patients who have experienced harm and the reality is that patients report that nothing is being done.”
The decision will now be submitted to the FDA, which is expected to make its final decision by August 11. The committee’s vote is only a recommendation, and the agency is not obligated to follow its advice, although it usually does.
According to the FDA, approximately 13 million people in the United States, many of whom are veterans, suffer from PTSD. This condition, which develops in some people exposed to serious injury or violence, can be debilitating: people often have intrusive memories and nightmares that can cause high levels of anxiety, suicidal thoughts, self-harm behavior and sleep disorders.
Talking therapy is the first line of treatment for the disease, 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 that patients often drop out of talk therapy alone. Additionally, response rates to medications rarely exceed 60%, and fewer than 20 to 30% of PTSD patients achieve complete 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 dampening the fear and anxiety response in the brain, said David Olson, director of the Institute. UC Davis for psychedelics and neurotherapeutics.