An independent Food and Drug Administration advisory panel rejected the use of MDMA-assisted treatment for post-traumatic stress disorder on Tuesday, highlighting the unparalleled regulatory challenges of a new treatment using the drug commonly known as Ecstasy.
Before the vote, panel members raised concerns about the two study designs submitted 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 given 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 proposed treatment’s benefits outweighed its risks.
Other participants expressed concerns about potential cardiovascular effects of the drug and potential bias among therapists and facilitators who led 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 participants.
Many of the panel members said they were particularly concerned about Lykos’ failure to collect detailed data from participants about the potential for abuse of a drug that produces feelings of euphoria and well-being.
“I absolutely agree that we need new and better treatments for PTSD,” said Paul Holtzheimer, associate director of research at the National PTSD Center, who voted no on the question of whether the benefits of MDMA treatment outweigh the risks.
“However, I also note that premature introduction of a treatment can actually stifle development, stifle implementation, and lead to early adoption of treatments that are either not fully known to be safe, not fully effective, or not used with their optimal effectiveness. added.
Although the vote is not binding on the FDA, the agency often follows the recommendations of its advisory committees. The agency’s final decision is expected in mid-August.
MDMA, or methylenedioxymethamphetamine, sometimes also referred to as mintoamphetamine is a synthetic psychoactive drug that promotes self-awareness, feelings of empathy, and social connection.
The illegal drug is listed as a Schedule I substance, defined as having an unacceptable medical use and a high potential for abuse. Should it win FDA approval, federal health authorities and Justice Department officials would have to take steps to downgrade the drug’s registration, much like the process now underway with cannabis.
The DEA can also set production quotas for drug ingredients, as it does with stimulant drugs used to treat ADHD.
With the panel’s focus on topics such as “euphoria,” “suicidal ideation” and “expectation bias,” Tuesday’s daylong session showed the nuances and complexities facing regulators as they navigate the terra incognita of a treatment that has only recently entered the market. mainstream psychiatry after the nation’s decades-long war on drugs.
An added wrinkle: the FDA is a drug regulator. It does not regulate psychotherapy and has not evaluated drugs whose effectiveness is linked to talking therapy.
If approved, the MDMA-assisted treatment would be the first new treatment for PTSD in nearly 25 years. The condition, which affects an estimated 13 million Americans, has been implicated in high suicide rates among military veterans, whose suffering has galvanized lawmakers from both parties and prompted a shift in public attitudes about treatment-based in psychedelic compounds.
According to the 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 received a placebo, 69 percent improved, and nearly 48 percent did not meet the criteria for a PTSD diagnosis, according to the submitted data.
The questions, concerns and apparent skepticism expressed by the 10-member panel echoed those raised by agency staff members, who last week issued a briefing paper aimed at helping the panel assess its effectiveness and potential negative impacts. in the health of MDMA treatment.
In her opening speech, Dr. Tiffany Farchione, director of the FDA’s division of psychiatry, noted the regulatory challenges posed by MDMA, saying “we’re learning as we go.” But in her testimony and in staff documents, she and other agency officials repeatedly noted that the study’s overall results were significant and lasting.
“Although the application presents a number of complex review issues, it includes two positive studies in which participants in the methamphetamine arm showed statistically significant and clinically meaningful improvement in PTSD symptoms,” he 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 has focused on so-called functional blinding, a problem that affects many studies involving psychoactive compounds. Although the roughly 400 patients in the studies were not told whether they had received MDMA or a placebo, to reduce the chance of biasing the results, the vast majority were fully aware of any altered state of mind that led them to the correct guess which arm of study were registered.
The FDA, which worked with Lykos to design the trials, has acknowledged flaws in the study designs and recently issued new guidelines to address the problems faced by psychedelic researchers.
A number of other critical voices have emerged in recent months. They include the Institute for Clinical and Economic Review, a nonprofit that reviews drug costs and effectiveness, which issued a report calling the treatment’s results “unclear” and questioning the results of Lykos’ study.
Other organizations, such as the American Psychiatric Association, did not oppose the approval, but asked the FDA to mitigate any negative consequences by establishing strict regulations, strict prescribing and administration controls, and close monitoring of patients.
The FDA staff analysis recommended that approval should be contingent on limited health care settings, patient monitoring, and diligent reporting of adverse events.
Just before they voted on Tuesday, the advisory panel heard from more than 30 speakers who offered wildly different views on the application.
Several critics have focused on Rick Doblin, a veteran psychedelic advocate who in 1986 founded the Multidisciplinary Association for Psychedelic Studies, the nonprofit organization that submitted the original application for MDMA-assisted therapy to the F.D.A. For-profit Lykos Therapeutics, formerly MAPS PBC, would market the drug if approved.
Brian Pace, a lecturer at Ohio State University, described the company applying for approval as a “treatment cult” and criticized Mr Doblin’s public comments underlining his zeal for psychedelics, including his belief that legalization and their regulation will bring world peace.
But the majority of those who spoke in favor of the app offered deeply personal accounts of how MDMA treatment had greatly alleviated their PTSD symptoms.
Among them was Cristina Pearse, who said she suffered from 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 felt like a tsunami of overwhelming panic was now just a puddle at my feet,” said Ms Pearse, who started an organization helping women recovering from trauma.
She ended her testimony by urging the FDA to approve the application.
“How many more people have to die before we approve an effective treatment?” asked. “As you weigh the risk, keep in mind that this treatment could save many lives. I lost most of my life to this disease. I am grateful to have it back now. But I wish this was an approved drug decades ago.”
