Evidence map›Paper›PMID 31065731›Full record

ArticlePsychopharmacology2019

MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials.

Michael C Mithoefer, Allison A Feduccia, Lisa Jerome, Anne Mithoefer, Mark Wagner, Zach Walsh, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin

Retracted 7 registry-linked trialsOpen access · hybridAbstract readRetracted PublicationClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. It is linked to 7 registered trials, which are not on this map. Cited by 138 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed, 10 pooled it
49.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00090064 phase2completednot on this map

Phase II Clinical Trial Testing the Safety and Efficacy of 3,4-Methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy in Subjects With Chronic Posttraumatic Stress Disorder

TypeinterventionalSponsorResilient PharmaceuticalsRan2004 to 2010Enrolled23ConditionsPosttraumatic Stress DisorderArmsMidomafetamine HCl, Lactose placebo pill, Therapy
NCT00353938 phase2completednot on this map

Phase II Pilot Randomized Double-Blind Placebo-Controlled Study of 3,4-methylenedioxymethamphetamine (MDMA)Assisted Psychotherapy in Posttraumatic Stress Disorder (PTSD)- Switzerland

TypeinterventionalSponsorResilient PharmaceuticalsRan2006 to 2011Enrolled14ConditionsPosttraumatic Stress DisorderArms3,4-methylenedioxymethamphetamine (125 mg), 3,4-methyelendioxymethamphetamine (25 mg), Therapy
NCT01211405 phase2completednot on this map

Randomized, Triple-Blind, Phase 2 Pilot Study Comparing 3 Different Doses of MDMA in Conjunction With Manualized Therapy in 24 Veterans, Firefighters and Police Officers With Chronic Posttraumatic Stress Disorder (PTSD)

TypeinterventionalSponsorResilient PharmaceuticalsRan2010 to 2016Enrolled26ConditionsPosttraumatic Stress DisorderArmsLow dose MDMA-assisted therapy, Medium dose MDMA-assisted therapy, Full dose MDMA-assisted therapy, Therapy
NCT01689740 phase2completednot on this map

A Randomized, Double-Blind, Active Placebo-Controlled Phase 2 Pilot Study of MDMA-assisted Psychotherapy in People With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)

TypeinterventionalSponsorResilient PharmaceuticalsRan2013 to 2017Enrolled10ConditionsPosttraumatic Stress Disorder (PTSD)ArmsActive Placebo Dose MDMA-assisted therapy (25 mg), Full Dose MDMA-assisted therapy (125 mg), Open-Label Full Dose MDMA-assisted therapy (125 mg), Psychotherapy
NCT01793610 phase2completednot on this map

A Randomized, Double-Blind, Dose Response Phase 2 Pilot Study of Manualized MDMA-Assisted Psychotherapy in Subjects With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)

TypeinterventionalSponsorResilient PharmaceuticalsRan2013 to 2017Enrolled29ConditionsPosttraumatic Stress DisorderArmsComparator Dose (40mg) MDMA HCl, Active Dose 2 (100 mg) MDMA HCl, Active Dose 1 (125 mg) MDMA HCl, Psychotherapy
NCT01958593 phase2terminatednot on this map

A Randomized, Double-Blind, Controlled Phase 2 Pilot Study of Manualized 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy in 12 Subjects With Treatment-Resistant Posttraumatic Stress Disorder (PTSD) - Canada

TypeinterventionalSponsorResilient PharmaceuticalsRan2014 to 2016Enrolled6ConditionsPosttraumatic Stress DisorderArmsPlacebo, Midomafetamine HCl, Psychotherapy
NCT05219175 phase2recruitingnot on this mapstarted 2024, after this paper: background citation

MDMA-Assisted Therapy 6 to 12 Months After Childbirth for People With Co-occurring Opioid Use and Post Traumatic Stress Disorders

TypeinterventionalSponsorUniversity of New MexicoRan2024 to 2027Enrolled15ConditionsStress Disorders, Post-Traumatic, Opioid Use DisorderArmsMDMA Assisted Therapy
3 · Its place in the literature

Who cites it

138 citing papers in PubMed, 10 syntheses or guidelines pooled it, 359 citations in OpenAlex.

  1. Pooled it
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  4. Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
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78 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 2 countries.

Michael C MithoeferMedical University of South Carolina, Charleston, SC, USA.
Allison A FeducciaMAPS Public Benefit Corporation, 1115 Mission St, Santa Cruz, CA, USA. alli@mapsbcorp.com.ORCID http://orcid.org/0000-0002-6918-0738
Lisa JeromeMAPS Public Benefit Corporation, 1115 Mission St, Santa Cruz, CA, USA.
Anne MithoeferPrivate Practice, Charleston, SC, USA.
Mark WagnerMedical University of South Carolina, Charleston, SC, USA.
Zach WalshUniversity of British Columbia-Okanagan, Kelowna, BC, Canada.
Scott HamiltonStanford School of Medicine, Stanford University, Stanford, CA, USA.
Berra Yazar-KlosinskiMultidisciplinary Association for Psychedelic Studies, Santa Cruz, CA, USA.
Amy EmersonMAPS Public Benefit Corporation, 1115 Mission St, Santa Cruz, CA, USA.
Rick DoblinMultidisciplinary Association for Psychedelic Studies, Santa Cruz, CA, USA.
Public Service Electric and Gas (United States) · USMedical University of South Carolina · USMultidisciplinary Association for Psychedelic Studies · USCollege of Charleston · USStanford University · USUniversity of British Columbia · CA

Funding

Multidisciplinary Association for Psychedelic Studies X
6 · The paper itself

Abstract

backgroundPosttraumatic stress disorder is a prevalent mental health condition with substantial impact on daily functioning that lacks sufficient treatment options. Here we evaluate six phase 2 trials in a pooled analysis to determine the study design for phase 3 trials of MDMA-assisted psychotherapy for PTSD.

methodsSix randomized, double-blind, controlled clinical trials at five study sites were conducted from April 2004 to February 2017. Active doses of MDMA (75-125 mg, n = 72) or placebo/control doses (0-40 mg, n = 31) were administered to individuals with PTSD during manualized psychotherapy sessions in two or three 8-h sessions spaced a month apart. Three non-drug 90-min therapy sessions preceded the first MDMA exposure, and three to four followed each experimental session.

resultsAfter two blinded experimental sessions, the active group had significantly greater reductions in CAPS-IV total scores from baseline than the control group [MMRM estimated mean difference (SE) between groups - 22.0 (5.17), P < 0.001]. The between-group Cohen's d effect size was 0.8, indicating a large treatment effect. After two experimental sessions, more participants in the active group (54.2%) did not meet CAPS-IV PTSD diagnostic criteria than the control group (22.6%). Depression symptom improvement on the BDI-II was greatest for the active group compared to the control group, although only trended towards significant group differences [MMRM, estimated mean difference (SE) between groups - 6.0 (3.03), P = 0.053]. All doses of MDMA were well tolerated, with some expected reactions occurring at greater frequency for the active MDMA group during experimental sessions and the 7 days following.

conclusionsMDMA-assisted psychotherapy was efficacious and well tolerated in a large sample of adults with PTSD. These studies supported expansion into phase 3 trials and led to FDA granting Breakthrough Therapy designation for this promising treatment.

trial registrationClinicalTrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.

Indexed as

AdultClinical Trials, Phase III as TopicCombined Modality TherapyDouble-Blind MethodFemaleFollow-Up StudiesHumansMaleMiddle AgedMulticenter Studies as TopicN-Methyl-3,4-methylenedioxyamphetaminePsychotherapyRandomized Controlled Trials as TopicSerotonin AgentsStress Disorders, Post-TraumaticN-Methyl-3,4-methylenedioxyamphetamineSerotonin AgentsAnxietyMDMAMDMA-assisted psychotherapyPosttraumatic stress disorderPsychedelic

Identifiers

PMID31065731
PMCPMC6695343
OpenAlexW2944263526

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

and 1 more above

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.