Treating posttraumatic stress disorder with MDMA-assisted psychotherapy: A preliminary meta-analysis and comparison to prolonged exposure therapy

Abstract

Since the wars in Iraq and Afghanistan, posttraumatic stress disorder (PTSD) has become a major area of research and development. The most widely accepted treatment for PTSD is prolonged exposure (PE) therapy, but for many patients it is intolerable or ineffective. ±3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AP) has recently re-emerged as a new treatment option, with two clinical trials having been published and both producing promising results. However, these results have yet to be compared to existing treatments. The present paper seeks to bridge this gap in the literature. Often the statistical significance of clinical trials is overemphasized, while the magnitude of the treatment effects is overlooked. The current meta-analysis aims to provide a comparison of the cumulative effect size of the MDMA-AP studies with those of PE. Effect sizes were calculated for primary and secondary outcome measures in the MDMA-AP clinical trials and compared to those of a meta-analysis including several PE clinical trials. It was found that MDMA-AP had larger effect sizes in both clinician-observed outcomes than PE did (Hedges' g=1.17 vs. g=1.08, respectively) and patient self-report outcomes (Hedges' g=0.87 vs. g=0.77, respectively). The dropout rates of PE and MDMA-AP were also compared, revealing that MDMA-AP had a considerably lower percentage of patients dropping out than PE did. These results suggest that MDMA-AP offers a promising treatment for PTSD.

Altered Insula Connectivity under MDMA

“…In light of recent hypotheses suggesting an 'insular view of anxiety' (Paulus and Stein, 2006), further understanding of how MDMA affects the insula might be crucial to elucidating the neurobiological underpinnings of re-emerging interest in MDMA as a therapeutic adjunct to psychotherapy in the treatment of anxiety disorders including PTSD (Mithoefer et al, 2011;Oehen et al, 2013, see Amoroso andWorkman, 2016 for a preliminary meta-analysis).…”

“…The first randomized controlled trials (RCTs) of MDMAassisted psychotherapy for treatment-resistant PTSD demonstrated decreases in both clinician-and participant-rated symptom severity (Mithoefer et al, 2011;Oehen et al, 2013). The efficacy of these interventions persisted at follow-up (Mithoefer et al, 2012), and effect sizes surpassed even those demonstrated by prolonged exposure therapy, the most widely accepted treatment for PTSD (Amoroso and Workman, 2016). Nonetheless, limitations pertaining to modest sample sizes and potential implicit biases warrant cautious interpretation of these preliminary, yet promising results.…”

Trace Amines and Their Receptors

“…Such development activities may also include environmental stress disorders such as post-traumatic stress disorder, in which an increased susceptibility to drug abuse is prevalent. In this regard, it is interesting to note that the possible beneficial effects of the psychotropic TAAR1 ligand MDMA in post-traumatic stress disorder are being actively investigated (Amoroso and Workman, 2016;Sessa, 2017).…”

Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

“…225 A recent meta-analysis determined that MDMA-assisted psychotherapy produced larger effect sizes in both clinician-observed outcomes and patient self-reports when compared to prolonged exposure therapy. 226 Furthermore, fewer patients in the MDMA-assisted psychotherapy group dropped out of the study. 226 These studies and others have indicated that MDMA was well tolerated when administered in a clinical setting as a single dose in the range of 75–125 mg. 19 Recently, MDMA was granted “breakthrough therapy” status by the FDA for the treatment of PTSD.…”