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MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
by
Amiaz, Revital
,
van der Kolk, Bessel
,
Kleiman, Sarah
in
692/308/153
,
692/308/2779/109/1942
,
Adult
2021
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (
n
= 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (
P
< 0.0001,
d
= 0.91) and to significantly decrease the SDS total score (
P
= 0.0116,
d
= 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.
Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.
Journal Article
Treating the trauma survivor : an essential guide to trauma-informed care
\"Treating the Trauma Survivor is a practical guide to assist mental health, health care, and social service providers in providing trauma-informed care. This resource provides essential information in order to understand the impacts of trauma by summarizing key literature in an easily accessible and user-friendly format. Providers will be able to identify common pitfalls and avoid re- traumatizing survivors during interactions. Based on the authors extensive experience and interactions with trauma survivors, the book provides a trauma-informed framework and offers practical tools to enhance collaboration with survivors and promote a safer helping environment. Mental health providers in health care, community, and addictions settings as well as health care providers and community workers will find the framework and the practical suggestions in this book informative and useful\"- Provided by publisher.
Associations between adverse childhood experiences and health outcomes in adults aged 18–59 years
2019
Adverse childhood experiences (ACEs) have been associated with poor health status later in life. The objective of the present study was to examine the relationship between ACEs and health-related behaviors, chronic diseases, and mental health in adults.
A cross-sectional study was performed with 1501 residents of Macheng, China. The ACE International Questionnaire (ACE-IQ) was used to assess ACEs, including psychological, physical, and sexual forms of abuse, as well as household dysfunction. The main outcome variables were lifetime drinking status, lifetime smoking status, chronic diseases, depression, and posttraumatic stress disorder. Multiple logistic regression models were used to examine the associations between overall ACE score and individual ACE component scores and risk behaviors/comorbidities in adulthood after controlling for potential confounders.
A total of 66.2% of participants reported at least one ACE, and 5.93% reported four or more ACEs. Increased ACE scores were associated with increased risks of drinking (adjusted odds ratio [AOR] = 1.09, 95% confidence intervals [CI]: 1.00-1.09), chronic disease (AOR = 1.17, 95% CI: 1.06-1.28), depression (AOR = 1.37, 95% CI: 1.27-1.48), and posttraumatic stress disorder (AOR = 1.32, 95% CI: 1.23-1.42) in adulthood. After adjusting for confounding factors, the individual ACE components had different impacts on risk behavior and health, particularly on poor mental health outcomes in adulthood.
ACEs during childhood were significantly associated with risk behaviors and poor health outcomes in adulthood, and different ACE components had different long-term effects on health outcomes in adulthood.
Journal Article
Effectiveness of Group Problem Management Plus, a brief psychological intervention for adults affected by humanitarian disasters in Nepal: A cluster randomized controlled trial
by
Wang, Xueqi
,
Dawson, Katie S.
,
Jordans, Mark J. D.
in
Adaptation, Psychological
,
Adolescent
,
Adult
2021
Globally, 235 million people are impacted by humanitarian emergencies worldwide, presenting increased risk of experiencing a mental disorder. Our objective was to test the effectiveness of a brief group psychological treatment delivered by trained facilitators without prior professional mental health training in a disaster-prone setting.
We conducted a cluster randomized controlled trial (cRCT) from November 25, 2018 through September 30, 2019. Participants in both arms were assessed at baseline, midline (7 weeks post-baseline, which was approximately 1 week after treatment in the experimental arm), and endline (20 weeks post-baseline, which was approximately 3 months posttreatment). The intervention was Group Problem Management Plus (PM+), a psychological treatment of 5 weekly sessions, which was compared with enhanced usual care (EUC) consisting of a family psychoeducation meeting with a referral option to primary care providers trained in mental healthcare. The setting was 72 wards (geographic unit of clustering) in eastern Nepal, with 1 PM+ group per ward in the treatment arm. Wards were eligible if they were in disaster-prone regions and residents spoke Nepali. Wards were assigned to study arms based on covariate constrained randomization. Eligible participants were adult women and men 18 years of age and older who met screening criteria for psychological distress and functional impairment. Outcomes were measured at the participant level, with assessors blinded to group assignment. The primary outcome was psychological distress assessed with the General Health Questionnaire (GHQ-12). Secondary outcomes included depression symptoms, posttraumatic stress disorder (PTSD) symptoms, \"heart-mind\" problems, social support, somatic symptoms, and functional impairment. The hypothesized mediator was skill use aligned with the treatment's mechanisms of action. A total of 324 participants were enrolled in the control arm (36 wards) and 319 in the Group PM+ arm (36 wards). The overall sample (N = 611) had a median age of 45 years (range 18-91 years), 82% of participants were female, 50% had recently experienced a natural disaster, and 31% had a chronic physical illness. Endline assessments were completed by 302 participants in the control arm (36 wards) and 303 participants in the Group PM+ arm (36 wards). At the midline assessment (immediately after Group PM+ in the experimental arm), mean GHQ-12 total score was 2.7 units lower in Group PM+ compared to control (95% CI: 1.7, 3.7, p < 0.001), with standardized mean difference (SMD) of -0.4 (95% CI: -0.5, -0.2). At 3 months posttreatment (primary endpoint), mean GHQ-12 total score was 1.4 units lower in Group PM+ compared to control (95% CI: 0.3, 2.5, p = 0.014), with SMD of -0.2 (95% CI: -0.4, 0.0). Among the secondary outcomes, Group PM+ was associated with endline with a larger proportion attaining more than 50% reduction in depression symptoms (29.9% of Group PM+ arm versus 17.3% of control arm, risk ratio = 1.7, 95% CI: 1.2, 2.4, p = 0.002). Fewer participants in the Group PM+ arm continued to have \"heart-mind\" problems at endline (58.8%) compared to the control arm (69.4%), risk ratio = 0.8 (95% CI, 0.7, 1.0, p = 0.042). Group PM+ was not associated with lower PTSD symptoms or functional impairment. Use of psychosocial skills at midline was estimated to explain 31% of the PM+ effect on endline GHQ-12 scores. Adverse events in the control arm included 1 suicide death and 1 reportable incidence of domestic violence; in the Group PM+ arm, there was 1 death due to physical illness. Study limitations include lack of power to evaluate gender-specific effects, lack of long-term outcomes (e.g., 12 months posttreatment), and lack of cost-effectiveness information.
In this study, we found that a 5-session group psychological treatment delivered by nonspecialists modestly reduced psychological distress and depression symptoms in a setting prone to humanitarian emergencies. Benefits were partly explained by the degree of psychosocial skill use in daily life. To improve the treatment benefit, future implementation should focus on approaches to enhance skill use by PM+ participants.
ClinicalTrials.gov NCT03747055.
Journal Article
Moving past PTSD : consciousness, understanding, and appreciation for military veterans and their families
From World War I until today, the United States has failed to provide adequate transition support to millions of veterans leaving military service. Instead of providing meaningful jobs, access to quality health care and education, and fair and equitable housing, veterans learn that when their military service is done, they are now fighting a new battle--a failed bureaucracy that has let them and other veterans down for the past 100 years. It's not as if we as a nation haven't tried. The Veterans Health Administration (VHA) has seen the largest increase in funding in its history and has been given several free passes when the budget axe arrives. Federal funding and grants for education have also enjoyed similar financial favor; and housing opportunities have been increased. Yet on a rudimentary level, we as a nation cannot stop believing that GI Joe and Jane can't wait to come back home and pick up right where they left off before their military services began. The truth is, that person is gone and is not coming back. Many veterans, particularly those with PTSD are lost when returning home. [This book] hopes to break this cycle. In their own words, veterans, caregivers, and the family members that love them are given the opportunity to tell us what is truly broken in the military to civilian transition. Advances in clinical treatment, the presentation of a new, fast-track job training program, and new awareness for the challenges facing all military veterans changes our way of understanding of who the twenty-first century veteran is. Through this understanding, we can change their lives and they can change ours. -- Back cover.
Posttraumatic stress disorder in the World Mental Health Surveys
2017
Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.
Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.
The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.
PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.
Journal Article
Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials
2020
RationalePosttraumatic 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.ObjectivesTo examine long-term change in PTSD symptoms and additional benefits/harms after 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treatment of PTSD.MethodsParticipants 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.ResultsThere 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.ConclusionsPTSD 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 registrationclinicaltrials.gov Identifier: NCT00090064, NCT00353938, NCT01958593, NCT01211405, NCT01689740, NCT01793610
Journal Article