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A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis

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Abstract

Rationale: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.

Objective: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD.

Methods: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck’s Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention.

Results: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -58.78, -35.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days.

Conclusion: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck’s Depression Inventory. Better powered RCTs are required to investigate further.

Illingworth, B. J., Lewis, D. J., Lambarth, A. T., Stocking, K., Duffy, J. M., Jelen, L. A., & Rucker, J. J. (2021). A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. Journal of psychopharmacology (Oxford, England), 35(5), 501–511. https://doi.org/10.1177/0269881120965915

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