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      Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline

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          Abstract

          Unsuccessfully treated posttraumatic stress disorder (PTSD) is a serious and life-threatening disorder. Two medications, paroxetine hydrochloride and sertraline hydrochloride, are approved treatments for PTSD by the Food and Drug Administration (FDA). Analyses of pharmacotherapies for PTSD found only small to moderate effects when compared with placebo. The Multidisciplinary Association for Psychedelic Studies (MAPS) obtained Breakthrough Therapy Designation (BTD) from the FDA for 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD on the basis of pooled analyses showing a large effect size for this treatment. This review covers data supporting BTD. In this treatment, MDMA is administered with psychotherapy in up to three monthly 8-h sessions. Participants are prepared for these sessions beforehand, and process material arising from the sessions in follow-up integrative psychotherapy sessions. Comparing data used for the approval of paroxetine and sertraline and pooled data from Phase 2 studies, MAPS demonstrated that MDMA-assisted psychotherapy constitutes a substantial improvement over available pharmacotherapies in terms of safety and efficacy. Studies of MDMA-assisted psychotherapy had lower dropout rates compared to sertraline and paroxetine trials. As MDMA is only administered under direct observation during a limited number of sessions, there is little chance of diversion, accidental or intentional overdose, or withdrawal symptoms upon discontinuation. BTD status has expedited the development of MAPS phase 3 trials occurring worldwide, leading up to a planned submission seeking FDA approval in 2021.

          Clinical Trial Registration: www.ClinicalTrials.gov, identifiers NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610.

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          Most cited references48

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          Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care.

          The current combat operations in Iraq and Afghanistan have involved U.S. military personnel in major ground combat and hazardous security duty. Studies are needed to systematically assess the mental health of members of the armed services who have participated in these operations and to inform policy with regard to the optimal delivery of mental health care to returning veterans. We studied members of four U.S. combat infantry units (three Army units and one Marine Corps unit) using an anonymous survey that was administered to the subjects either before their deployment to Iraq (n=2530) or three to four months after their return from combat duty in Iraq or Afghanistan (n=3671). The outcomes included major depression, generalized anxiety, and post-traumatic stress disorder (PTSD), which were evaluated on the basis of standardized, self-administered screening instruments. Exposure to combat was significantly greater among those who were deployed to Iraq than among those deployed to Afghanistan. The percentage of study subjects whose responses met the screening criteria for major depression, generalized anxiety, or PTSD was significantly higher after duty in Iraq (15.6 to 17.1 percent) than after duty in Afghanistan (11.2 percent) or before deployment to Iraq (9.3 percent); the largest difference was in the rate of PTSD. Of those whose responses were positive for a mental disorder, only 23 to 40 percent sought mental health care. Those whose responses were positive for a mental disorder were twice as likely as those whose responses were negative to report concern about possible stigmatization and other barriers to seeking mental health care. This study provides an initial look at the mental health of members of the Army and the Marine Corps who were involved in combat operations in Iraq and Afghanistan. Our findings indicate that among the study groups there was a significant risk of mental health problems and that the subjects reported important barriers to receiving mental health services, particularly the perception of stigma among those most in need of such care. Copyright 2004 Massachusetts Medical Society
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            Patient preference for psychological vs pharmacologic treatment of psychiatric disorders: a meta-analytic review.

            Evidence-based practice involves the consideration of efficacy and effectiveness, clinical expertise, and patient preference in treatment selection. However, patient preference for psychiatric treatment has been understudied. The aim of this meta-analytic review was to provide an estimate of the proportion of patients preferring psychological treatment relative to medication for psychiatric disorders. A literature search was conducted using PubMed, PsycINFO, and the Cochrane Collaboration library through August 2011 for studies written in English that assessed adult patient preferences for the treatment of psychiatric disorders. The following search terms and subject headings were used in combination: patient preference, consumer preference, therapeutics, psychotherapy, drug therapy, mental disorders, depression, anxiety, insomnia, bipolar disorder, schizophrenia, substance-related disorder, eating disorder, and personality disorder. In addition, the reference sections of identified articles were examined to locate any additional articles not captured by this search. Studies that assessed preferred type of treatment and included at least 1 psychological treatment and 1 pharmacologic treatment were included. Of the 644 articles identified, 34 met criteria for inclusion. Authors extracted relevant data including the proportion of participants reporting preference for psychological or pharmacologic treatment. The proportion of adult patients preferring psychological treatment was 0.75 (95% CI, 0.69-0.80), which was significantly higher than equivalent preference (ie, higher than 0.50; P < .001). Sensitivity analyses suggested that younger patients (P = .05) and women (P < .01) were significantly more likely to choose psychological treatment. A preference for psychological treatment was consistently evident in both treatment-seeking and unselected (ie, non-treatment-seeking) samples (P < .001 for both) but was somewhat stronger for unselected samples. Aggregation of patient preferences across diverse settings yielded a significant 3-fold preference for psychological treatment. Given evidence for enhanced outcomes among those receiving their preferred psychiatric treatment and the trends for decreasing utilization of psychotherapy, strategies to maximize the linkage of patients to preferred care are needed. © Copyright 2013 Physicians Postgraduate Press, Inc.
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              Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions.

              The present study used data from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,653) to examine lifetime Axis I psychiatric comorbidity of posttraumatic stress disorder (PTSD) in a nationally representative sample of U.S. adults. Lifetime prevalences ± standard errors of PTSD and partial PTSD were 6.4% ± 0.18 and 6.6% ± 0.18, respectively. Rates of PTSD and partial PTSD were higher among women (8.6% ± 0.26 and 8.6% ± 0.26) than men (4.1% ± 0.19 and 4.5% ± 0.21). Respondents with both PTSD and partial PTSD most commonly reported unexpected death of someone close, serious illness or injury to someone close, and sexual assault as their worst stressful experiences. PTSD and partial PTSD were associated with elevated lifetime rates of mood, anxiety, and substance use disorders, and suicide attempts. Respondents with partial PTSD generally had intermediate odds of comorbid Axis I disorders and psychosocial impairment relative to trauma controls and full PTSD. Published by Elsevier Ltd.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                12 September 2019
                2019
                : 10
                : 650
                Affiliations
                [1] 1Department of Research Development and Regulatory Affairs, MAPS Public Benefit Corporation , Santa Cruz, CA, United States
                [2] 2Multidisciplinary Association for Psychedelic Studies , Santa Cruz, CA, United States
                [3] 3MAPS Public Benefit Corporation , Santa Cruz, CA, United States
                [4] 4Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina , Charleston, SC, United States
                Author notes

                Edited by: Felix Müller, University Psychiatric Clinic Basel, Switzerland

                Reviewed by: Tomislav Majic, Charité–Universitätsmedizin Berlin, Germany; Katrin H. Preller, University of Zurich, Switzerland

                *Correspondence: Lisa Jerome, ilsa@ 123456mapsbcorp.com

                This article was submitted to Psychopharmacology, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2019.00650
                6751381
                30723425
                8fd113e3-460c-40d2-a2f1-4df183cd9eae
                Copyright © 2019 Feduccia, Jerome, Yazar-Klosinski, Emerson, Mithoefer and Doblin

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 June 2019
                : 13 August 2019
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 70, Pages: 9, Words: 5391
                Categories
                Psychiatry
                Review

                Clinical Psychology & Psychiatry
                methylenedioxymethamphetamine,posttraumatic stress disorder,breakthrough therapy,sertraline,paroxetine,anxiety

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