Research Suggests Past Antidepressant Usage Reduces Efficacy of MDMA-Assisted Psychotherapy for PTSD

Research Suggests Past Antidepressant Usage Reduces Efficacy of MDMA-Assisted Psychotherapy for PTSD

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New research published in Psychopharmacology suggests antidepressant use may reduce the efficacy of MDMA therapy for PTSD.

The study (Feduccia et al., 2020) showed that recent exposure to serotonin reuptake inhibitor (SSRI) antidepressants may reduce response to MDMA-assisted psychotherapy.

MDMA’s primary mechanism acts on the same reuptake transporters targeted by the two FDA-approved medications for PTSD: sertraline and paroxetine, both of which are SSRIs.

The researchers pooled data from four separate phase 2 trials of MDMA-assisted psychotherapy for PTSD. Participant data was then separated into two distinct groups: one group had tapered off antidepressant medications, the other had not. Researchers then conducted between-group analyses to evaluate how participants’ responses to the MDMA therapy differed.

While demographics and baseline PTSD and depression severity were similar across both groups, the non-taper group’s response to MDMA-assisted psychotherapy was much more prominent. 63.6% of participants in the non-taper group no longer met PTSD criteria at 1-2 months after treatment, while only 25% of the taper group experienced the same success. Depression scores were also lower in the non-taper group. Table 3 demonstrates these results:

Feduccia et al., 2020

As such, this important piece of research suggests that exposure to SSRI antidepressants may reduce the efficacy of MDMA-assisted psychotherapy. The researchers explain:

“Recent prior use and tapering of medications that target monoamine reuptake transporters resulted in blunted therapeutic and physiological responses to MDMA in phase 2 trials.”

Interestingly, the study found no significant correlation between the time at which participants ceased SSRI intake and the observed dampening of MDMA-assisted psychotherapy’s efficacy. This may suggest that SSRIs have long-term effects on the brain.


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