Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder
In four randomised, double‑blind Phase 2 trials (n=63), 2–3 sessions of MDMA‑assisted psychotherapy significantly improved self‑reported sleep quality and produced larger reductions in PTSD symptoms than low‑dose/control MDMA, with sleep gains maintained at 12 months. At the primary endpoint CAPS‑IV scores fell by −34.0 versus −12.4 and PSQI total score changed by −3.5 versus +0.6 for active versus control (p = .003 for both).
Authors
- Berra Yazar-Klosinski
- Michael Mithoefer
- Lisa Jerome
Published
Abstract
Sleep disturbances (SDs) are among the most distressing and commonly reported symptoms in posttraumatic stress disorder (PTSD). Despite increased attention on sleep in clinical PTSD research, SDs remain difficult to treat. In Phase 2 trials, 3,4‐methylenedioxymethamphetamine (MDMA)–assisted psychotherapy has been shown to greatly improve PTSD symptoms. We hypothesized that MDMA‐assisted psychotherapy would improve self‐reported sleep quality (SQ) in individuals with PTSD and be associated with declining PTSD symptoms. Participants in four studies ( n = 63) were randomized to receive 2–3 sessions of active MDMA (75–125 mg; n = 47) or placebo/control MDMA (0–40 mg, n = 16) during all‐day psychotherapy sessions. The PSQI was used to assess change in SQ from baseline to the primary endpoint, 1–2 months after the blinded sessions. Additionally, PSQI scores were measured at treatment exit (TE) and 12‐month follow‐up. Symptoms of PTSD were measured using the CAPS‐IV. At the primary endpoint, CAPS‐IV total severity scores dropped more after active MDMA than after placebo/control (−34.0 vs. −12.4), p = .003. Participants in the active dose group showed more improvement in SQ compared to those in the control group (PSQI total score Δ M = −3.5 vs. 0.6), p = .003. Compared to baseline, SQ had improved at TE, p < .001, with further significant gains reported at 12‐month follow‐up (TE to 12‐months Δ M = −1.0), p = .030. Data from these randomized controlled double‐blind studies provide evidence for the beneficial effects of MDMA‐assisted psychotherapy in treating SDs in individuals with PTSD.
Research Summary of 'Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder'
Introduction
Sleep disturbance is highly prevalent among people with posttraumatic stress disorder (PTSD) and is implicated in the onset, maintenance, and poorer treatment outcomes of the disorder. Earlier research shows that PTSD is associated with a range of sleep problems—insomnia, nightmares, fragmented sleep, atypical sleep behaviours and daytime dysfunction—and that these problems can impede fear extinction and recovery. Standard PTSD treatments often reduce core PTSD symptoms without fully resolving sleep disturbance, and many patients either drop out of or fail to respond to available sleep-specific interventions, indicating an unmet need for therapies that address both PTSD and sleep problems. Ponte and colleagues used pooled data from four Phase II, randomised, double-blind trials of MDMA-assisted psychotherapy to examine whether active MDMA (75–125 mg) given in conjunction with manualised psychotherapy would improve self-reported sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), and whether changes in sleep quality would be associated with reductions in PTSD symptom severity (measured by the CAPS-IV). The investigators hypothesised that PSQI decreases at the primary endpoint would correlate with reductions in CAPS-IV total scores and explored whether a clinically meaningful PSQI improvement (a decrease of 3 points or more) predicted greater PTSD symptom change at treatment exit and 12 months.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topic
- Authors
- APA Citation
Ponte, L., Jerome, L., Hamilton, S., Mithoefer, M. C., Yazar‐Klosinski, B. B., Vermetten, E., & Feduccia, A. A. (2021). Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder. Journal of Traumatic Stress, 34(4), 851-863. https://doi.org/10.1002/jts.22696
References (10)
Papers cited by this study that are also in Blossom
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Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T. et al. · Journal of Psychopharmacology (2012)
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Kangaslampi, S., Zijlmans, J. · European Child and Adolescent Psychiatry (2023)
Sottile, R. J., Vida, T. · Frontiers in Psychiatry (2022)
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