Dataset Information

Effects of MDMA-assisted therapy for PTSD on self-experience.

ABSTRACT:

Introduction

There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills and altered self-capacities constitute major obstacles to successful completion of available treatments. The current analysis evaluated the differential effects of MDMA-assisted therapy and Therapy with placebo on 3 transdiagnostic outcome measures and explored the contribution of changes in self-experience to improvement in PTSD scores.

Methods

Participants were randomized to receive manualized therapy with either MDMA or placebo during 3 experimental sessions in combination with 3 preparation and 9 integration therapy visits. Symptoms were measured at baseline and 2 months after the last experimental session using the 20-item Toronto Alexithymia Scale (TAS-20), the 26-item Self Compassion Scale (SCS), and the 63-item Inventory of Altered Self-Capacities (IASC).

Results

90 participants were randomized and dosed (MDMA-assisted therapy, n = 46; Therapy with placebo, n = 44); 84.4% (76/90) had histories of developmental trauma, and 87.8% (79/90) had suffered multiple traumas. MDMA-assisted therapy facilitated statistically significant greater improvement on the TAS-20, the SCS, and most IASC factors of interpersonal conflicts; idealization disillusionment; abandonment concerns; identity impairment; self-awareness; susceptibility to influence; affect dysregulation; affect instability; affect skill deficit; tension reduction activities; the only exception was identity diffusion.

Conclusion

Compared with Therapy with placebo, MDMA-assisted therapy had significant positive effects on transdiagnostic mental processes of self-experience which are often associated with poor treatment outcome. This provides a possible window into understanding the psychological capacities facilitated by psychedelic agents that may result in significant improvements in PTSD symptomatology.

SUBMITTER: van der Kolk BA

PROVIDER: S-EPMC10781106 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Effects of MDMA-assisted therapy for PTSD on self-experience.

van der Kolk Bessel A BA Wang Julie B JB Yehuda Rachel R Bedrosian Leah L Coker Allison R AR Harrison Charlotte C Mithoefer Michael M Yazar-Klosinki Berra B Emerson Amy A Doblin Rick R

PloS one 20240110 1

<h4>Introduction</h4>There is a resurgence of interest in the therapeutic potential of psychedelic substances such as 3,4-methylenedioxymethamphetamine (MDMA). Primary findings from our randomized, double-blind, placebo-controlled, multi-site Phase 3 clinical trial of participants with severe PTSD (NCT03537014) showed that MDMA-assisted therapy induced significant attenuation in the Clinician-Administered PTSD Scale for DSM-5 compared to Therapy with placebo. Deficits in emotional coping skills ...[more]

PMID: 38198456

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Project description:BackgroundChronic posttraumatic stress disorder (PTSD) is a disabling condition that generates considerable morbidity, mortality, and both medical and indirect social costs. Treatment options are limited. A novel therapy using 3,4-methylenedioxymethamphetamine (MDMA) has shown efficacy in six phase 2 trials. Its cost-effectiveness is unknown.Methods and findingsTo assess the cost-effectiveness of MDMA-assisted psychotherapy (MAP) from the health care payer's perspective, we constructed a decision-analytic Markov model to portray the costs and health benefits of treating patients with chronic, severe, or extreme, treatment-resistant PTSD with MAP. In six double-blind phase 2 trials, MAP consisted of a mean of 2.5 90-minute trauma-focused psychotherapy sessions before two 8-hour sessions with MDMA (mean dose of 125 mg), followed by a mean of 3.5 integration sessions for each active session. The control group received an inactive placebo or 25-40 mg. of MDMA, and otherwise followed the same regimen. Our model calculates net medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Efficacy was based on the pooled results of six randomized controlled phase 2 trials with 105 subjects; and a four-year follow-up of 19 subjects. Other inputs were based on published literature and on assumptions when data were unavailable. We modeled results over a 30-year analytic horizon and conducted extensive sensitivity analyses. Our model calculates expected medical costs, mortality, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Future costs and QALYs were discounted at 3% per year. For 1,000 individuals, MAP generates discounted net savings of $103.2 million over 30 years while accruing 5,553 discounted QALYs, compared to continued standard of care. MAP breaks even on cost at 3.1 years while delivering 918 QALYs. Making the conservative assumption that benefits cease after one year, MAP would accrue net costs of $7.6 million while generating 288 QALYS, or $26,427 per QALY gained.ConclusionMAP provided to patients with severe or extreme, chronic PTSD appears to be cost-saving while delivering substantial clinical benefit. Third-party payers are likely to save money within three years by covering this form of therapy.

Project description:BackgroundSocial anxiety disorder (SAD) is a serious and prevalent psychiatric condition that heavily impacts social functioning and quality of life. Though efficacious treatments exist for SAD, remission rates remain elevated and a significant portion of those affected do not access effective treatment, suggesting the need for additional evidence-based treatment options. This paper presents a protocol for an open-label pilot study of MDMA-assisted therapy (MDMA-AT) for social anxiety disorder. The study aims to assess preliminary treatment outcomes, feasibility and safety, and psychological and physiological processes of change in the treatment of SAD with MDMA-AT. A secondary aim includes the development of a treatment manual for MDMA-AT for SAD.MethodThe outlined protocol is a randomized, open-label delayed treatment study. We will recruit 20 participants who meet criteria with moderate-to-severe social anxiety disorder (SAD) of the generalized subtype. Participants will be randomly assigned to an immediate treatment (n = 10) or delayed treatment condition (n = 10). Those in the immediate treatment condition will proceed immediately to active MDMA-AT consisting of three preparation sessions, two medicine sessions in which they receive oral doses of MDMA, and six integration sessions over approximately a 16-week period. The delayed treatment condition will receive the same intervention after a 16-week delay. Our primary outcome is SAD symptom reduction as measured by the Liebowitz Social Anxiety Scale administered by blinded raters at post-treatment and 6 month follow up. Secondary outcomes include changes in functional impairment, feasibility and safety measures, and novel therapeutic processes of change including shame and shame-related coping, belongingness, self-concealment, and self-compassion at post-treatment. Exploratory outcomes are also discussed.DiscussionThe results of this pilot trial advance the field's understanding of the acceptability and potential effectiveness of MDMA-AT for social anxiety disorder and provide an overview of relevant therapeutic mechanisms unique to SAD. We hope findings from this protocol will inform the design of subsequent larger-scale randomized controlled trials (RCT) examining the efficacy of MDMA-AT for SAD.Clinical trial registrationhttps://clinicaltrials.gov/, NCT05138068.

Project description:RATIONALE:Posttraumatic stress disorder (PTSD) is a chronic condition that has wide-ranging negative effects on an individual's health and interpersonal relationships. Treatments with long-term benefits are needed to promote the safety and well-being of those suffering from PTSD. OBJECTIVES:To examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD. METHODS:Participants received two to three active doses of MDMA (75-125 mg) during blinded or open-label psychotherapy sessions with additional non-drug therapy sessions. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale for DSM IV (CAPS-IV) at baseline, 1 to 2 months after the last active MDMA session (treatment exit), and at least 12 months post final MDMA session (LTFU). A mixed-effect repeated-measures (MMRM) analysis assessed changes in CAPS-IV total severity scores. The number of participants who met PTSD diagnostic criteria was summarized at each time point. Participants completed a long-term follow-up questionnaire. RESULTS:There was a significant reduction in CAPS-IV total severity scores from baseline to treatment exit (LS mean (SE) = - 44.8 (2.82), p < .0001), with a Cohen's d effect size of 1.58 (95% CI = 1.24, 1.91). CAPS-IV scores continued to decrease from treatment exit to LTFU (LS mean (SE) = - 5.2 (2.29), p < .05), with a Cohen's d effect size of 0.23 (95% CI = 0.04, 0.43). The number of participants who no longer met PTSD criteria increased from treatment exit (56.0%) to LTFU (67.0%). The majority of participants reported benefits, including improved relationships and well-being, and a minority reported harms from study participation. CONCLUSIONS:PTSD symptoms were reduced 1 to 2 months after MDMA-assisted psychotherapy, and symptom improvement continued at least 12 months post-treatment. Phase 3 trials are investigating this novel treatment approach in a larger sample of participants with chronic PTSD. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.

Dataset Information

Effects of MDMA-assisted therapy for PTSD on self-experience.

Introduction

Methods

Results

Conclusion

Publications

Effects of MDMA-assisted therapy for PTSD on self-experience.

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