Effects of Selective Serotonin Reuptake Inhibitor Use on 3,4-Methylenedioxymethamphetamine-Assisted Therapy for Posttraumatic Stress Disorder
This brief review synthesises basic and clinical neuroscience evidence on interactions between SSRIs and MDMA‑assisted therapy for PTSD and finds strong neurobiological plausibility that chronic SSRI use may dampen responses to MDMA‑assisted treatment. The authors note current evidence is limited and largely about acute pharmacodynamic interactions and call for urgent research to inform clinical counselling and treatment planning.
Authors
- Anna Feduccia
Published
Abstract
Background
Among the renewed applications of psychedelic medicines in psychiatry, 3,4-methylenedioxymethamphetamine (MDMA)–assisted therapy for posttraumatic stress disorder (PTSD) has demonstrated the most promise in early small-scale studies. Recent exploratory analyses from prior clinical trials of MDMA-assisted therapy for PTSD have suggested that recent use of selective serotonin reuptake inhibitors (SSRIs)—the only medication class with United States Food and Drug Administration (FDA) approval to treat PTSD—can significantly dampen the efficacy of this novel therapy. Although psychedelic medicines are not yet FDA approved, MDMA is very likely to be the first to achieve FDA approval—perhaps within the next 2 years. Given this timeline, the field would benefit from more knowledge about potential interactions between this novel therapy and our current treatments.
Methods
This brief report reviews selected literature in the basic and clinical neurosciences relevant to the interaction of SSRIs and MDMA.
Findings
The possibility that SSRI use could dampen future responses to MDMA-assisted therapy for PTSD raises many important questions about the biological mechanisms as well as ethical implications around the most appropriate way to counsel patients. In this brief report, we compare the evidence for SSRIs and MDMA-assisted therapy in the treatment of PTSD and discuss what is known about the neurobiological interactions between these 2 medicines.
Conclusions
There is strong neurobiological plausibility for the hypothesis that chronic SSRI use dampens response to MDMA-assisted therapy, although current knowledge in the field is limited and primarily relates to acute pharmacodynamic interactions. Our commentary highlights the urgent need for future work dedicated to addressing this important clinical topic.
Research Summary of 'Effects of Selective Serotonin Reuptake Inhibitor Use on 3,4-Methylenedioxymethamphetamine-Assisted Therapy for Posttraumatic Stress Disorder'
Introduction
The treatment of posttraumatic stress disorder (PTSD) remains a major unmet need in psychiatry: trauma-focused psychotherapies can reduce symptoms but have high dropout and nonresponse rates, and pharmacological options are limited. Two selective serotonin reuptake inhibitors (SSRIs), sertraline and paroxetine, are the only medications approved by the United States Food and Drug Administration for PTSD; fluoxetine and the serotonin–noradrenaline reuptake inhibitor venlafaxine have also been studied and are recommended first-line in guidelines. Overall, these medications produce modest symptom reductions and low remission rates, leaving many people with persistent disability and prompting interest in novel treatments. Price and colleagues situate MDMA-assisted therapy as one of the most promising emerging interventions for chronic, treatment‑resistant PTSD. Early phase trials and a Phase II/III programme have reported large effect sizes and comparatively high remission rates after a small number of MDMA‑assisted psychotherapy sessions. This brief report reviews selected basic and clinical neuroscience and clinical-trial data to assess a specific clinical question: whether current or recent SSRI use can attenuate the therapeutic and subjective effects of MDMA, and what the clinical and ethical implications of such an interaction would be if MDMA-assisted therapy becomes widely accessible.
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Study Details
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- APA Citation
Price, C. M., Feduccia, A. A., & DeBonis, K. (2022). Effects of Selective Serotonin Reuptake Inhibitor Use on 3,4-Methylenedioxymethamphetamine-Assisted Therapy for Posttraumatic Stress Disorder. Journal of Clinical Psychopharmacology, 42(5), 464-469. https://doi.org/10.1097/JCP.0000000000001595
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Feduccia, A. A., Jerome, L., Mithoefer, M. C. et al. · Psychopharmacology (2020)
Sarparast, A., Thomas, K., Malcolm, B. et al. · Psychopharmacology (2022)
Cited By (1)
Papers in Blossom that reference this study
Warner-Schmidt, J., Pittenger, C., Stogniew, M. et al. · Frontiers in Psychiatry (2023)
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