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

This meta-analysis (2016) examines the effect sizes of interventions aimed at treating posttraumatic stress disorder with MDMA-assisted psychotherapy and comparing it to the efficacy of prolonged exposure therapy. Results indicated that both therapy options exhibit large effect sizes in outcome measures related to both clinician-observed PTSD symptoms and self-reported symptoms. While both of these therapies are efficient means to treat PTSD, exposure therapy induces a considerably higher state of arousal within a much shorter therapy session, and MDMA-assisted therapy offers a more patient-centered approach that leaves more time to explore different aspects of trauma, in contrast.

Abstract

“Introduction: 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.

Methods: 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.

Results: 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.

Discussion: These results suggest that MDMA-AP offers a promising treatment for PTSD.”

Authors: Timothy Amoroso & Michael Workman

Summary

Introduction

Posttraumatic stress disorder (PTSD) is a chronic and debilitating disorder characterized by four symptom clusters, and has a high lifetime prevalence rate of 6.8% in the general population. The Department of Veteran Affairs estimates that only 9.5% of veterans diagnosed with PTSD are actually receiving treatment. This may be due to the stigma associated with seeking treatment, as well as institutional barriers such as lack of skill and sensitivity by VA staff.

Prolonged exposure therapy (PE) is one of the most widely accepted treatments for PTSD. However, only a small minority of veteran patients are treated with PE because it is emotionally demanding and often aggravates the patient’s symptoms before they improve.

A meta-analysis of two clinical trials comparing MDMA-assisted psychotherapy to prolonged exposure therapy for posttraumatic stress disorder (PTSD) found that MDMA-AP had larger effect sizes in both clinician-observed outcomes and patient self-report outcomes than PE did.

MDMA is a ring-substituted amphetamine that was originally used as a psychotherapeutic adjunct by psychiatrists and psychologists, but was categorized as a Schedule I drug and banned from medical use in 1985. It is hypothesized that MDMA increases a sense of trust and bonding between the therapist and patient.

MDMA is believed to have psychopharmacological properties that make it well suited for treating PTSD. It attenuates activation in brain regions involved with PTSD, while activating executive regions of the hippocampus.

MDMA-assisted psychotherapy (MDMA-AP) is a treatment course that typically consists of one to three drug sessions lasting eight hours and several follow-up non-drug sessions.

To determine if a new treatment is worth pursuing, it is important to compare it to existing treatments. MDMA-AP has yet to be compared to an existing “best-available” treatment.

Often, statistically significant results are overemphasized, while the magnitude of the results is overlooked. Therefore, effect size is often a more useful metric when comparing treatment studies with large differences in sample size.

This analysis compares the effect sizes of PE in treating PTSD to those of the published MDMA-AP trials.

Procedure

A preliminary meta-analysis of MDMA-AP was conducted, and results were compared to a reliable meta-analysis of PE, the most widely accepted treatment of PTSD.

Three databases were used to find the only meta-analysis on prolonged exposure to MDMA and the two published articles on MDMA-AP. The studies had to be randomized, double blind, and placebo controlled, and have enough participants to provide inferential statistics.

Effect size calculations were performed on MDMA studies and compared to PE. The effect sizes were corrected according to Hedges and Olkin (1985) using the formula: outcomes.

Powers et al. (2010) did not calculate an average dropout rate, so the percentages of participants dropping out were calculated for each study within the PE meta-analysis.

Hypothesis 2: MDMA-AP will have a larger cumulative effect size than PE will for secondary outcome measures

The overall effect size for PE was large, as was the effect size for secondary outcome measures. The effect size for MDMA-AP was also large, as was the effect size for cumulative outcome measures.

Validity of meta-analysis

Heterogeneity was calculated using the I2 statistic instead of Cochran’s Q, because it is known to be a better reporter of heterogeneity. The I2 value for the MDMA-AP studies was 0%.

Publication bias may cause effect sizes reported in meta-analyses to be overestimated. A fail-safe N should be reported in meta-analyses to account for the possible null effects of unpublished work.

Powers et al. (2010) calculated that 446 current or future unpublished studies with an effect size of 0 would be required to bring the overall effect size of the meta-analysis within the non-significant range.

Discussion

MDMA-AP has comparable treatment outcomes to PE, with large effect sizes on primary outcome measures.

PE is a treatment that puts the patient into a heightened state of arousal, with little time to process the experience before leaving the therapy session. MDMA-AP offers a patient-centered approach that allows the patient to explore aspects of the trauma.

PE has been shown to have high dropout rates, but MDMA-AP had lower percentages of participants dropping out of treatment. This may be due to the long eight-hour therapy sessions, which make the patient feel as though the therapist is more committed to their recovery.

The PE studies used psychological placebos or waitlist controls, whereas the MDMA-AP studies used active placebos. The PE studies reported effect sizes based on those who received treatment and those who received nothing.

A meta-analysis of MDMA-psychotherapy studies found that participants on various psychotropic medications had inflated effect sizes.

The meta-analysis on PE included 13 studies with much larger sample sizes, whereas the two MDMA-AP trials had much smaller sample sizes. Additionally, the inclusion criteria for the two MDMA-AP studies were different, and the average duration of PTSD symptoms was different.

People with PTSD have limited treatment options, such as exposure therapies, and the response rate to pharmacotherapy is low. New innovations, such as MDMA-AP, are imperative to help the many suffering from PTSD.