Study Shows MDMA-Assisted Therapy Less Effective for Patients Who Use Antidepressants

In December 2020, the Multidisciplinary Association for Psychedelic Studies (MAPS) announced positive results from the first of its two Phase 3 trials of MDMA-assisted therapy for the treatment of posttraumatic stress disorder (PTSD), strengthening the outlook for U.S. Food and Drug Administration (FDA) approval by 2023. Now, a new peer-reviewed analysis published in Psychopharmacology shows that MDMA-assisted therapy was less effective for patients who had recently used selective serotonin reuptake inhibitors (SSRIs) to treat their PTSD symptoms.

The study found that 63.6% of participants who received MDMA-assisted therapy no longer met PTSD diagnostic criteria after treatment—unless they had been using antidepressants. Of those participants who tapered off their antidepressants to receive the therapy, only 25% no longer had PTSD. The finding has significant implications for PTSD patients seeking MDMA-assisted therapy in the future, given that at least 13.6% of US adults are prescribed antidepressants, according to the CDC.

“Given the encouraging results of early trials of MDMA-assisted therapy for PTSD, and the estimated 8 million adults in the U.S. alone who suffer from the condition, there’s likely to be extraordinary demand for the treatment once it’s approved,” says Allison Feduccia, Ph.D., study co-author and co-founder of the education platform Psychedelic.Support. “Since it is a time- and cost-intensive treatment, patients may have a limited number of chances to utilize MDMA-assisted therapy. Our goal in sharing this new data is to give PTSD patients the best possible chance at successful treatment with this promising new breakthrough therapy.”

With MDMA still in Phase 3 trials, the SSRIs sertraline (Zoloft) and paroxetine (Paxil) are currently the only FDA-approved medications for PTSD. However, because they are known to reduce the effects of MDMA, patients must taper off these medications prior to receiving MDMA-assisted therapy.

The findings could have significant implications for PTSD patient care once MDMA-assisted therapy is approved for use, according to the study authors. These could include asking patients to go through a longer antidepressant tapering period prior to receiving MDMA-assisted therapy, and further educating patients still considering antidepressants on the impact on their potential eligibility for MDMA-assisted therapy, should they wish to consider it.

“These results will allow me and other clinicians to provide our PTSD patients with better information and realistic expectations for treatment with MDMA-assisted therapy,” says Veronika Gold, MFT, co-therapist on the MDMA clinical trial and co-founder of Polaris Insight Center. “In addition to awaiting the final results of Phase 3 clinical trials, we’ll need further research to learn more about how differences in tapering schedules or length of time on antidepressants might impact the effectiveness of this treatment.”

The study authors suggest several mechanisms for the negative impact of recent SSRI use on MDMA-assisted therapy for PTSD, including: (1) the downregulation of binding sites (serotonin, dopamine, and/or norepinephrine) related to SSRI use; (2) reduced MDMA treatment-relevant increases in blood pressure in patients with recent SSRI use; and/or (3) the possibility of withdrawal symptoms from SSRIs reducing the effectiveness of MDMA-assisted therapy.

“By determining specific factors, such as antidepressant tapering, that impact the treatment response rate of MDMA-assisted therapy, clinicians can choose approaches that maximize symptom improvements and reduce the chance that patients will require follow-up treatments,” says Feduccia.

The new analysis was based on the previously published cumulative results of six Phase 2 clinical trials of MDMA-assisted therapy for PTSD, and published by Allison Feduccia, Ph.D. (Psychedelic.Support), Lisa Jerome, Ph.D. (MAPS Public Benefit Corporation), Michael Mithoefer, M.D. (Medical University of South Carolina and MAPS Public Benefit Corporation), and Julie Holland, M.D. (Private Practice).

Due to the study’s small sample size, varying taper lengths, and the possibility that the taper group had more severe PTSD, the study’s results are preliminary. Nevertheless, the analysis showed a clear reduction in the effectiveness of MDMA-assisted therapy for patients who had used SSRIs and makes a strong case for further research based on the upcoming results of Phase 3 clinical trials.

For those interested in participating in an MDMA-assisted therapy clinical trial, Psychedelic.Support recommends not tapering SSRIs until they are screened and enrolled in the studies. Any medication tapering should be done only in consultation with a clinician, so they can monitor for side effects or discontinuation symptoms.

Psychedelic.Support offers a directory of licensed health professionals and community groups that provide mental health services (online and in-person) related to psychedelic medicine and integration. Psychedelic.Support advances psychedelic knowledge and practical skills through its education platform, featuring courses, workshops, and trainings taught by leading psychedelic researchers and practitioners.

· Article: View online (open access)

· Citation: Feduccia, A.A., Jerome, L., Mithoefer, M.C. et al. Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy. Psychopharmacology (2020). https://doi.org/10.1007/s00213-020-05710-w