MDMA-assisted psychotherapy for the treatment of PTSD: A systematic review and meta-analysis of randomized controlled trials (RCTs).

MDMA-assisted psychotherapy (MDMA-AT) significantly reduces PTSD symptoms and improves response and remission rates in people with chronic, treatment-resistant PTSD, according to a meta-analysis of nine randomized controlled trials involving 297 participants. The treatment led to a large reduction in clinician-rated PTSD severity scores compared to control conditions (inactive MDMA doses or placebo). Patients receiving MDMA-AT were about 1.6 times more likely to show a meaningful response and over twice as likely to achieve remission. No significant differences were found between groups in rates of treatment-emergent adverse events, severe adverse events, or suicidal ideation, indicating a favorable safety profile.

Study at a glance

Abstract

Post-traumatic stress disorder (PTSD) is a mental health disorder resulting from exposure to traumatic events, manifesting in various debilitating symptoms. Despite available treatments, many individuals experience inadequate response or significant side effects. Previous reviews suggest promising outcomes with MDMA-assisted psychotherapy (MDMA-AT), but limitations prompt the need for a comprehensive evaluation. We searched various online databases and registries such as MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to retrieve RCTs that fit our inclusion criteria. We performed meta-analyses using Review Manager by applying a random-effects model. Dichotomous and continuous outcomes were pooled as risk ratios (RR) and standard mean difference (SMD), respectively. Nine studies with a total of 297 participants with PTSD were included in our meta-analysis. The control group consisted of inactive doses of MDMA (25-40 mg) or placebo. Our meta-analysis showed that MDMA-AT led to a significant reduction in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) severity scores as compared to the control group (SMD -1.10, 95% CI: -1.62 to -0.59). More patients in the MDMA-AT group exhibited significant response (RR 1.59, 95% CI: 1.22, 2.08) and remission (RR 2.32, 95% CI: 1.47 to 3.66) as compared to patients in the control group. There was no significant difference regarding the incidence of ≥1 treatment-emergent adverse events (TEAE), ≥1 severe TEAE, and suicidal ideation between the two groups. MDMA-AT demonstrates significant efficacy in improving PTSD symptoms, enhancing both response and remission rates in individuals with chronic, treatment-resistant PTSD, while maintaining a favorable safety profile.