Here is another very exciting guest post. More of these feel good, dear readers, in that the plural in The Frontier Psychiatrists' name? It always took other perspectives into account and imagined a variety of authors. Today, we welcome my friend Alison McInnes, M.D., a psychiatrist and pioneer in ketamine research. She works with
, my wife, at Osmind. This column is a think—or maybe feel?— piece on the (soon-to-be decided) MDMA-AT FDA submission, with previous coverage on the topic available here:Should MDMA-AT Be Saved, Part III
Saving MDMA (and other psychedelic therapies), Part VI
Saving MDMA VII: This Isn't The First Drug to Have Problems Getting Approved
Today’s article is from a doctor who’s thought about it more than most…
I am a psychiatrist and a researcher. These roles have allowed me to study various psychiatric disorders throughout my career. I can’t fail to notice that research studies often take on the qualities of the disorders under investigation. An early example I noted when studying the biological basis of bipolar disorder. This involved working with study staff and helping to recruit patients. I began to notice that the study was moving at high speed and that there was an elated and sometimes volatile mood among staff members. There was more sociability and conviviality than would usually be the case. There were even some “risky behaviors,” nothing alarming, but it was more than I expected. I then switched gears and joined a study of autism. It was striking how differently this study evolved. Rules were followed to the tee, there was no risk of anything, and the pace was methodical. The staff did their work with a rigid attention to detail. Socializing, readers may already guess, was not prominent among the team. Now, these observations are not so surprising. There is a phenomenon in psychiatry known as assortative mating. In essence, this means that mated pairs tend to be more alike regarding psychiatric disorders and symptoms. It isn’t such a stretch to think that individuals might be drawn to study psychiatric disorders with which they share symptoms or experiences (like trauma). With this in mind, let’s take an imagined helicopter upward and examine how the ecosystem encompassing the MAPS/Lykos FDA application behaves.
First of all, a subject in the MDMA-AT trials was sexually abused during their treatment session. How could this happen to a patient coming to be healed from sexual trauma - even though sessions were videotaped? There were allegations that this event was not reported in a timely fashion. Then, there were other unrelated allegations. Some trial therapists suggested that adverse events like the emergence of suicidal ideation were not methodically reported. Some suggested that participants were encouraged to enhance their reporting of response to the drug. Clinical data measuring ‘drug-liking’ was not gathered, though the FDA had suggested it. But then the FDA stopped suggesting that EKG and liver function data be gathered (their words, not mine). ICER, Institute for Clinical and Economic Review, and FDA AdComm considered all this information and expressed concerns about functional unblinding, even though it was always clear that the sponsors were using an inactive placebo. They delivered an overwhelming no vote on the safety and effectiveness of the MDMA-AT combination.
The response from the community was very emotional. One group of patient advocates suggested that this decision resulted from pressure from big pharma. Most treatments fail to obtain FDA approval, but in this case, public belief in the efficacy of this medication is so strong that it makes it hard for some to consider the concerns raised. In the meantime, I wonder what effect the deluge of shock and outrage about the ICER and AdComm critiques has had on patients with PTSD. Irritability, distrust, fear, re-experiencing?
Mixing the perceptual and emotional distortions/attributions that can be induced by psychedelics with those inherent in PTSD may not be the best for every patient. I hope from the heart and the head that we can be calm and collected while allowing the regulatory process to unfold and that MDMA-AT ends up being approved with an appropriate risk evaluation and mitigation safety program. I also think there is a subset of PTSD patients who may not want to “Feel Love” (title of the excellent book by Rachel Nuwer on the journey of PTSD from party drug to therapeutic). I am glad that there is at least one novel psychoplastogen without psychoactive effects being developed for PTSD, and I hope that other drug developers will be encouraged to enter the space. We need more options for PTSD.
This is well written, but there have been many more flaws pointed out in the ICER's logic. I recently co-authored an article pointing out a lot of these issues (https://www.journalofpsychedelicpsychiatry.org/current-issue). I worry blocking this treatment is going to lead to more harm than any possible risk mitigation from delaying the approval. The goal posts will just keep getting pushed further and further back while patients continue to struggle, only having a few "FDA approved" options to choose from.
could you clarify what are those novel psychoplastogens for PTSD without psychoactive effects?