An independent Food and Drug Administration advisory panel on Tuesday rejected the use of MDMA-assisted therapy for post-traumatic stress disorder, highlighting the unparalleled regulatory challenges of a new therapy that uses an illegal drug commonly known as ecstasy.
Before the vote, panel members expressed concerns about the designs of the two studies presented by the drug’s sponsor, Lykos Therapeutics. Many questions focused on the fact that study participants were generally able to correctly guess whether they had been administered MDMA, also known as ecstasy or molly.
The panel voted 9-2 on whether MDMA-assisted therapy was effective and voted 10-1 on whether the benefits of the proposed treatment outweighed its risks.
Other panelists expressed concern about the potential cardiovascular effects of the drug and possible bias among therapists and facilitators who guided the sessions and may have positively influenced patient outcomes. A case of misconduct involving a patient and a therapist in the study also weighed on the minds of some panelists.
Many of the committee members said they were especially concerned that Lykos had not collected detailed data from participants about the potential for abuse of a drug that generates feelings of happiness and well-being.
“I absolutely 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 against the question of whether the benefits of MDMA therapy outweigh the risks.
“However, I also note that premature introduction of a treatment can actually stifle development, stifle implementation, and lead to premature adoption of treatments that are not fully known to be safe, are not fully effective, or are not used for their intended purpose.” optimal efficiency”. he added.
While the vote is not binding on the FDA, the agency typically follows the recommendations of its advisory panels. A final decision from the agency is expected in mid-August.
MDMA, or methylenedioxymethamphetamine, also sometimes called midomafetamine, is a synthetic psychoactive drug that promotes self-awareness, feelings of empathy, and social connection.
The illegal drug is included in Schedule I, defined as a substance that has no accepted medical use and has a high potential for abuse. If it were to win FDA approval, federal health authorities and Justice Department officials would have to take certain steps to downgrade the drug, much like the process currently underway with cannabis.
The DEA could also set production quotas for drug ingredients, as it does for stimulant medications used to treat ADHD.
With the panel’s focus on topics such as “euphoria,” “suicidal ideation” and “expectancy bias,” Tuesday’s daylong session demonstrated the nuances and complexities regulators face as they grapple with the terra incognita of a therapy. who recently entered mainstream psychiatry. after decades of war on drugs in the country.
An added detail: the FDA is a drug regulator. It does not regulate psychotherapy and has not evaluated medications whose effectiveness is linked to psychotherapy.
If approved, MDMA-assisted therapy would be the first new treatment for post-traumatic stress disorder in nearly 25 years. The condition, which affects about 13 million Americans, has been implicated in the huge suicide rates among military veterans, whose suffering has galvanized lawmakers of both parties and caused a sea change in public attitudes about therapies. that depend on psychedelic compounds.
According to studies presented by Lykos, patients who received MDMA plus 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. Of those who took the placebo, 69 percent improved and nearly 48 percent no longer qualified for a diagnosis of post-traumatic stress disorder, according to the data presented.
The questions, concerns and obvious skepticism expressed by the 10-member panel echoed those raised by agency staff members, who last week released a briefing document intended to help the panel evaluate 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 and said, “We’ve been learning as we go.” But in her testimony and in her staff documents, she and other agency officials repeatedly noted that the overall results of the study were significant and lasting.
“Although the application presents a number of complex review issues, it includes two positive studies in which participants in the midomafetamine group experienced a statistically and clinically significant improvement in their PTSD symptoms,” he said. “And that 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 plagues many studies involving psychoactive compounds. Although the approximately 400 patients who participated in the studies were not told whether they had received MDMA or a placebo, to reduce the chance of bias in the results, the vast majority were very aware of any altered mental states, leading them to make correct decisions. Guess which arm of the study they were enrolled in.
The FDA, which worked with Lykos to design the trials, recognized deficiencies in the study designs and recently issued new guidelines to address the problems facing psychedelic researchers.
In recent months, other critical voices have emerged. They include the Institute for Clinical and Economic Review, a nonprofit that examines the costs and effectiveness of medications, which issued a report calling the treatment’s effects “inconclusive” and questioning the results of Lykos’ study.
Other organizations, such as the American Psychiatric Association, have not outright opposed approval, 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 the drugs. patients.
The FDA staff analysis recommended that approval should depend on restricted health care settings, patient monitoring, and diligent reporting of adverse events.
Just before voting Tuesday, the advisory panel heard from more than 30 speakers who offered sharply divergent views on the request.
Several critics focused on Rick Doblin, a longtime psychedelic advocate who in 1986 founded the Multidisciplinary Association for Psychedelic Studies, the nonprofit that submitted the original application for MDMA-assisted therapy to the FDA. The organization later created a for-profit entity that became Lykos earlier this year.
Brian Pace, a professor at Ohio State University, described the company seeking approval as a “therapeutic cult” and criticized Mr. Doblin’s public comments highlighting his enthusiasm for psychedelics, including the belief that legalizing and regulating them would bring the world peace.
But most of those who spoke in favor of the app offered deeply personal accounts of how MDMA therapy had greatly calmed the symptoms of their post-traumatic stress disorder.
Among them was Cristina Pearse, who said she suffered from post-traumatic stress disorder after being sexually assaulted when she was 9 years old. Over the years, she said she had been prescribed a litany of psychiatric medications and at one point she attempted suicide.
MDMA therapy, he said, changed his life. “What used to seem like a tsunami of overwhelming panic was now simply a puddle at my feet,” said Pearse, who founded an organization that helps women recover from trauma.
He ended his testimony by urging the FDA to approve the application.
“How many more people need to die before we approve an effective therapy?” she asked. “When weighing the risk, keep in mind that this therapy can save many lives. I lost most of my life to this disease. I’m grateful to be able to claim it now. But I wish this was a drug approved decades ago.”