FDA panel rejects use of MDMA for PTSD treatment

An independent Food and Drug Administration advisory panel on Tuesday rejected the use of MDMA-assisted therapy for post-traumatic stress disorder, highlighting the unprecedented regulatory challenges of a new therapy using the drug commonly known as Ecstasy .

Before the vote, panel members expressed concerns about the design of the two studies submitted by the drug’s sponsor, Lykos Therapeutics. Many questions focused on whether study participants were generally able to correctly guess whether they had been given MDMA, also known as ecstasy or molly.

The panel voted 9 to 2 on the effectiveness of MDMA-assisted treatment, and 10 to 1 on whether the benefits of the proposed treatment outweighed its risks.

Other panelists expressed concerns about the drug’s potential cardiovascular effects and possible bias among therapists and facilitators who guided the sessions and who may have positively influenced patient outcomes. A case of misconduct involving a patient and therapist in the study also weighed on the minds of some panelists.

Many committee members expressed particular concern about Lykos’ failure to collect detailed data from participants about the abuse potential of a drug that generates feelings of happiness and well-being.

“I completely agree that we need new and better treatments for PTSD,” said Paul Holtzheimer, deputy director of research at the National Center for PTSD, a panelist who voted no on the question of whether the benefits of MDMA therapy outweighed the risks.

“However, I also note that the premature introduction of a treatment can actually stifle development, stifle implementation and lead to the premature adoption of treatments that are not completely known to be safe, that do not are not fully effective or not used optimally,” he said. added.

Although the vote is not binding on the FDA, the agency often follows the recommendations of its advisory committees. A final decision from the agency is expected by mid-August.

MDMA, or methylenedioxymethamphetamine, also sometimes called midomafetamine, is a synthetic psychoactive drug that promotes self-awareness, feelings of empathy, and social connections.

The illegal drug is listed as a Schedule I substance, defined as having no accepted medical use and a high potential for abuse. If it gains FDA approval, federal health authorities and Justice Department officials would have to follow certain steps to delist the drug, much like the process is currently underway for cannabis.

The DEA could also set production quotas for drug ingredients, as it does for stimulant medications used to treat ADHD.

With a focus on topics such as “euphoria,” “suicidal ideation” and “expectation bias,” Tuesday’s all-day session demonstrated the nuances and complexities facing regulators as they grapple with the terra incognita of a therapy that has only recently entered mainstream psychiatry. after decades of the country’s war on drugs.

An additional problem: The FDA is a drug regulator. It does not regulate psychotherapy and has not evaluated medications whose effectiveness is linked to talk therapy.

If approved, MDMA-assisted therapy would be the first new treatment for PTSD in nearly 25 years. The disease, which affects some 13 million Americans, has been implicated in skyrocketing suicide rates among veterans, whose suffering has galvanized lawmakers of both parties and sparked a sea change in public attitudes toward with regard to therapies based on psychedelic compounds.

According to studies presented by Lykos, patients who received MDMA and psychotherapy reported significant improvements in their mental health. The most recent drug trial found that more than 86 percent of those who took MDMA achieved a measurable reduction in the severity of their PTSD symptoms.

About 71 percent of participants improved enough to no longer meet the criteria for a diagnosis. Among those who took the placebo, 69 percent improved and nearly 48 percent no longer qualified for a PTSD diagnosis, according to the data submitted.

The questions, concerns and obvious skepticism expressed by the 10-member panel echoed those raised by agency staffers, who last week released a backgrounder aimed at helping the panel evaluate the The effectiveness and potential adverse health effects of MDMA therapy.

In her opening remarks, Dr. Tiffany Farchione, director of the FDA’s Division of Psychiatry, highlighted the regulatory challenges posed by MDMA, saying that “we’ve been learning as we go.” But in her testimony and in staff documents, she and other agency officials repeatedly emphasized that the study’s overall results were significant and lasting.

“While the application presents a number of complex review issues, it includes two positive studies in which participants in the midomafetamine group experienced statistically significant and clinically meaningful improvement in their PTSD symptoms,” she said. . “And this improvement appears to be durable for at least several months after the end of the acute treatment period. »

Much of the criticism of Lykos’ study designs focused on so-called functional unblinding, a problem that affects many studies involving psychoactive compounds. Although the approximately 400 patients who participated in the studies were not informed whether they had received MDMA or a placebo, to reduce the risk of bias in the results, the vast majority of them were fully aware of any altered state of mind, which led them to correctly guess which study group they were enrolled in.

The FDA, which worked with Lykos to design the trials, recognized the flaws in the study designs and recently issued new guidelines to address the issues facing psychedelic researchers.

A number of other critical voices have emerged in recent months. Among them, the Institute for Clinical and Economic Review, a nonprofit organization that examines the costs and effectiveness of drugs, issued a report calling the treatment’s effects “inconclusive” and questioning the results of the study of Lykos.

Other organizations, such as the American Psychiatric Association, have not opposed approval outright, but have called on the FDA to mitigate any potential negative consequences by developing rigorous regulations, strict prescribing and dispensing controls, and close monitoring of patients.

The FDA staff analysis recommended that approval be contingent on restricted health care parameters, patient monitoring, and diligent reporting of adverse events.

Just before Tuesday’s vote, the advisory committee heard from more than 30 speakers who expressed widely divergent views on the request.

Several critiques have focused on Rick Doblin, a veteran psychedelic advocate who in 1986 founded the Multidisciplinary Association for Psychedelic Studies, the nonprofit organization that filed the initial application for MDMA-assisted therapy to the F .DA. The for-profit company Lykos Therapeutics, formerly MAPS PBC, would market the drug if approved.

Brian Pace, a professor at Ohio State University, described the company seeking his approval as a “therapeutic cult” and criticized Mr. Doblin’s public comments emphasizing his zeal for psychedelics, including his belief that legalizing them and regulating them would bring world peace.

But the majority of those who spoke in favor of the app gave deeply personal testimonies about how MDMA therapy had largely alleviated their PTSD symptoms.

Among them was Cristina Pearse, who said she suffered PTSD after being sexually assaulted when she was 9 years old. Over the years, she said she was prescribed a litany of psychiatric medications and at one point attempted suicide.

MDMA therapy, she said, changed her life. “What once felt like a tsunami of overwhelming panic was now just a puddle at my feet,” said Ms. Pearse, who started an organization that helps women recover from trauma.

She ended her testimony by urging the FDA to approve the application.

“How many more people will have to die before we can approve an effective therapy? ” she asked. “When assessing risk, keep in mind that this therapy can save many lives. I lost most of my life to this disease. I’m grateful to have it back now. But I wish this was a drug approved decades ago.