Administration of MDMA. This drug is being studied as a treatment for PTSD, and the FDA is currently considering whether to approve it.
Travis Dove for The Washington Post via Getty Images/The Washington Post
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Travis Dove for The Washington Post via Getty Images/The Washington Post
A panel of experts advising the Food and Drug Administration on the use of the hallucinogen MDMA for post-traumatic stress disorder concluded Tuesday that available evidence does not show the drug is effective or that its benefits outweigh the risks.
This is a major setback for the drug’s supporters and for Lycos Therapeutics, the company that sponsored the drug’s clinical trials, and could jeopardize FDA approval of the treatment, which would have helped bring the drug into mainstream psychiatric care.
After receiving public comment and discussion, the committee decided by a 9-2 vote that MDMA is not effective in treating PTSD, even when combined with talk therapy, and by a 10-1 vote that the benefits of MDMA treatment do not outweigh the risks.
The FDA relies on the committee’s advice but is not required to follow its recommendations.
But it’s especially surprising given the many concerns raised during the day-long meeting.
Remarks from FDA officials and advisory committee members during the meeting highlighted several major obstacles, including deficiencies in clinical studies that could jeopardize potential approval.
Agency officials highlighted uncertainties and gaps in the data, unanswered questions about potential abuse and a lack of evidence supporting the psychological approaches used in the therapy sessions.
Some members of the committee explicitly raised allegations that had emerged about possible fraud and bias in the exams that could have skewed the results.
FDA scientists did not provide details but acknowledged that the agency is investigating some of the claims that have surfaced in petitions to the FDA and outside reports on clinical trials.
The importance of the moment was understood by those in attendance.
There are only two FDA-approved treatments for the disease, and MDMA would be the first to hit the market in decades — and a landmark for broader efforts to expand access to psychedelics.
“We’re breaking new ground,” said Kim Witczak, a consumer representative on the FDA advisory committee. “We want to get it right.”
Lykos representatives highlighted positive results in clinical data collected in two nearly identical randomized controlled trials.
For example, one study showed that 67% of participants in an MDMA treatment group no longer met diagnostic criteria for PTSD after three MDMA sessions, compared with approximately 32% in a placebo group, who received treatment sessions but no active medication.
“Overall, these results [that] “Combining MDMA with psychological interventions significantly reduces PTSD symptoms and functional impairment in people with PTSD,” said Béla Yazar-Krosinski, chief scientific officer at Lycos.
But FDA officials and outside advisers were not dwelling on these encouraging results.
Although steps were taken to “blind” subjects in this study, there has been considerable controversy surrounding the fact that many of the subjects knew they were receiving the experimental drug, which could lead to a condition known as “functional unblinding” and ultimately affect the results.
“There are certainly two positive studies, but those results come in the context of dramatic advances in functional blinding,” said Dr. David Millis, a clinical reviewer for the FDA.
Another potential problem is the lack of data on how patients experience the drug’s acute effects, including feelings such as “euphoria” or “high,” which could help the FDA evaluate the drug’s abuse potential.
“We noticed a remarkably low number of abuse-related adverse events,” Millis said, noting that the FDA has advised study sponsors to collect this type of data.
Although MDMA is currently listed as a Schedule III drug, agency studies have found that it has the same abuse potential as Schedule II stimulants, including cocaine.
“We’re actually seeing more and more severe cases of MDMA overdose, so we’re not so much concerned about the acute safety, but rather the chronic safety as patients continue to abuse MDMA,” said Maryann Amirshahi, a professor of emergency medicine at Georgetown University and a committee member.
Approximately 40% of participants in MDMA studies had a history of use prior to the study.
In addition to the positive findings on the short-term effects of MDMA, Lycos also released data from a follow-up observational study aimed at exploring the durability of treatment.
The data, which has not yet been published in a peer-reviewed journal, “suggests evidence that MDMA lasts for at least six months,” said Yazar Krosinski of Lycos.
But FDA staff noted there were problems with the long-term data, including a 25% dropout rate and the fact that some participants sought treatment and, in some cases, used illicit drugs such as MDMA.
Data shared by Lykos showed a range of adverse events.
Most of the study participants had experienced suicidal thoughts in their lifetime, but “the frequency of these symptoms was similar between the two groups” over the course of the study, said Dr. Alia Lilienstein, senior medical director at Lycos Therapeutics.
“Notably, no suicidal behaviour or suicide attempts were reported in the MDMA group,” she said.
This issue has become particularly hotly contested in light of recent allegations that certain adverse events are not being reported. A petition calling for the advisory meeting submitted to the FDA cites anonymous former drug company employees outlining these and other concerns:
Already there is a well-documented case in which two therapists involved in a Phase 2 trial allegedly engaged in inappropriate contact with subjects under the influence of MDMA: a video of the two therapists in bed with the subjects was eventually released on a podcast.
“Let’s not minimize this misconduct. This is sexual misconduct. This is particularly important,” said sociologist and committee member Elizabeth Joniak Grant.
Several other panelists asked similar questions.
Last month, a report from the Institute for Clinical and Economic Review, a group that evaluates clinical data and drug prices, concluded after a lengthy review of trial data that there was insufficient evidence to assess the overall net benefits of MDMA-assisted therapy.
The report said trial participants, including therapists and researchers, may have encouraged reporting of positive events and downplayed adverse events.
The drug company denied the allegations and said it was responsible for the data.
According to a public comment submitted to the FDA by one study participant, therapists encouraged participants to view “worsening symptoms as evidence of cure and a ‘spiritual awakening,'” and that she and other participants suffered from suicidal thoughts after the study.
Panelist Dr. Walter Dunn, a psychiatrist at UCLA, asked about the ICER report’s assertion that some participants may have been discouraged from taking part in long-term durability studies.
“We asked about those, too,” says Lycos’ Lilienstein. “All participants who were interested in participating were given the opportunity to confirm their consent, and although some chose not to participate after confirming their consent, everyone else was given the opportunity.”
