Bessel van der Kolk, MD: What MDMA-Assisted Therapy Taught us About PTSD

The US Food and Drug Administration (FDA) Psychopharmacologic Drugs Advisory Committee (PDAC) will convene on Tuesday, June 4, to discuss the evidence of clinical effectiveness supporting the use of midomafetamine (MDMA) for the treatment of patients with PTSD.¹

The advisory committee’s vote of support or dissent to the benefits of MDMA in the treatment of patients with PTSD—as well as their vote on a proposed risk evaluation and mitigation strategy (REMS) proposed by the FDA—will likely influence the eventual FDA decision on the New Drug Application (NDA) for MDMA-assisted therapy as a treatment for PTSD, from Lykos Therapeutics, later this summer.²

The data supporting the FDA application, which will be reviewed by the PDAC next week, include pivotal phase 3 trial results from the MAPP1 and MAPP2 studies that showed MDMA-assisted therapy provided statistically significantly improved outcomes on measures of alexithymia, self-compassion and some items of self-capacities relevant to the resolution of PTSD symptoms in affected patients.³

Leading into the historic advisory committee discussion and eventual FDA decision on the Lykos application, HCPLive spoke with Bessel van der Kolk, MD, co-founder and chair of the Trauma Research Foundation, and globally-recognized author and researcher of trauma. In the first segment of his interview, van der Kolk discussed how clinical research into MDMA has actually helped his field better understand the manifestation and effect of PTSD in patients.

As he explained, it’s been well-established in prior research that patients with lifelong trauma beginning primarily at childhood abuse and neglect generally do not respond well to any available psychiatric treatment—enough to the extent that van der Kolk advised such patients be excluded from their clinical trials. However, approximately 88% of the patients included in his team's research had such histories of trauma.

“And the startling thing about the study was that those people did particularly well, and they've never done well before,” van der Kolk said. “Adult-onset PTSD, where something terrible happens, tends to respond quite well to any number of interventions. But chronic childhood trauma responds very poorly. And so, to my mind, the greatest finding of the study was that MDMA really helped people to get in touch more with much more complex issues than the trauma—having led a traumatized existence where they never felt safe, even with our own family.”

Van der Kolk explained the original DSM diagnosis for PTSD describes patients who have suffered “from extraordinary events out of the usual realm of human experience.” To him, this limits the true scope of patients with PTSD, including this cohort that had experienced unprecedented treatment success with MDMA-assisted therapy.

Regarding the specific role of MDMA in patients with PTSD, van der Kolk discussed the nature of the drug to improve patient self-capacities that have been significantly impacted by trauma and therefore may hinder the effectiveness of standard-care psychotherapy. He explained that early childhood trauma significantly impacts mental capacities that help to control emotions, establish a sense of identity, and regulate emotions and focus.

“So, you have a much more complex set of mental problems besides the particular memory of the trauma,” van der Kolk said. “And those set of mental functions really prevents people from getting better, because if you cannot control your emotions, you become extremely fearful when you start recalling the traumatic incidents. And you may actually freak out, shut down become very agitated—you cannot go there.”

An outstanding observation from their trials, van der Kolk said, is the trend of patients who are finally able to adequately and measuredly recall their traumatic experiences, to “find the words” to describe their symptoms of PTSD that may foster more effective psychotherapeutic care.

Lastly, van der Kolk discussed the observed role of baseline alexithymia in treatment outcomes among patients receiving MDMA-assisted therapy, as well as how the acute effects of this therapy positive impacts the psychiatrist’s delivery of psychotherapy.

References

1. ^{Kunzmann K. FDA Advisory Committee Meeting to Review MDMA-Assisted Therapy for PTSD. HCPLive. Published May 6, 2024. https://www.hcplive.com/view/fda-advisory-committee-meeting-review-mdma-assisted-therapy-ptsd}
2. ^{Derman C. MDMA-Assisted Therapy for PTSD Awaits FDA Decision. HCPLive. Published December 21, 2023. https://www.hcplive.com/view/mdma-assisted-therapy-for-ptsd-awaits-fda-decision}
3. ^{van der Kolk BA, Wang JB, Yehuda R, et al. Effects of MDMA-assisted therapy for PTSD on self-experience. PLoS One. 2024;19(1):e0295926. Published 2024 Jan 10. doi:10.1371/journal.pone.0295926}