Trial PaperPTSDSubstance Use Disorders (SUD)Neurocognitive DisordersSafety & Risk ManagementPersonality & Trait FactorsInterpersonal Functioning & Social ConnectednessMDMA

Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study

In a prospective long-term follow‑up (mean 45.4 months) of the first MDMA‑assisted psychotherapy trial for chronic, treatment‑resistant PTSD (n=19; 16 CAPS completers), symptom reductions observed at study exit were largely maintained (mean CAPS 24.6 vs 23.7; p=0.91) though two participants relapsed. No participants reported harm or evidence of drug dependency, suggesting durable clinical benefit and a favourable safety profile.

Authors

  • Rick Doblin
  • Berra Yazar-Klosinski
  • Michael Mithoefer

Published

Journal of Psychopharmacology
individual Study

Abstract

We report follow-up data evaluating the long-term outcomes for the first completed trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for chronic, treatment-resistant post-traumatic stress disorder (PTSD) (Mithoefer et al., 2011). All of the 19 subjects who received MDMA-assisted treatment in the original trial participated in the long-term follow-up (LTFU), with 16 out of 19 completing all of the long-term outcome measures, which were administered from 17 to 74 months after the original study’s final MDMA session (mean = 45.4; SD = 17.3). Our primary outcome measure used was the Clinician-Administered PTSD Scale (CAPS). Secondary outcome measures were the Impact of Events Scale-Revised (IES-R) and the Neuroticism Extroversion Oppenness Personality Inventory-Revised (NEO PI-R) Personality Inventory. We also collected a long-term follow-up questionnaire. Results for the 16 CAPS completers showed there were no statistical differences between mean CAPS score at LTFU (mean = 23.7; SD = 22.8) ( tmatched = 0.1; df = 15, p = 0.91) and the mean CAPS score previously obtained at Study Exit (mean = 24.6, SD = 18.6). On average, subjects maintained statistically and clinically-significant gains in symptom relief, although two of these subjects did relapse. It was promising that we found the majority of these subjects with previously severe PTSD who were unresponsive to existing treatments had symptomatic relief provided by MDMA-assisted psychotherapy that persisted over time, with no subjects reporting harm from participation in the study.

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Research Summary of 'Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study'

Introduction

Post-traumatic stress disorder (PTSD) is often chronic and disabling, with many patients remaining symptomatic despite available pharmacological and psychotherapeutic treatments. Prior reports suggested that 3,4-methylenedioxymethamphetamine (MDMA), given in conjunction with psychotherapy, could produce substantial clinical benefits. MDMA is pharmacologically a monoamine releaser with prominent serotonergic action, and it also elevates oxytocin and alters neural responses related to threat and social cognition (for example, reduced amygdala activation and altered recognition of emotional facial expressions). These pharmacological and behavioural effects have been hypothesised to enhance psychotherapy by improving access to painful material, modulating arousal, and strengthening therapeutic alliance. Mithoefer and colleagues report a long-term follow-up (LTFU) of participants from their earlier randomised trial of MDMA-assisted psychotherapy. This study aimed to evaluate durability of PTSD symptom improvement, the presence of any long-term harms (including neurocognitive decline or substance abuse), and participants’ subjective appraisals of benefit, by reassessing participants many months to years after their final MDMA session.

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Study Details

References (9)

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