Oxytocin to Enhance Integrated Exposure-Based Treatment of Co-occurring Alcohol Use Disorder and PTSD

催产素可增强对同时发生的酒精使用障碍和创伤后应激障碍的综合暴露治疗

• 批准号: 10262945
• 负责人: SUDIE E BACK
• 金额: $ 68.17万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10262945
• 关键词: Address; Aftercare; Alcohol consumption; Alcohols; Animals; Area; Back; Behavior; Behavioral; Biological Markers; Chronic Post Traumatic Stress Disorder; Clinic; Clinical Research; Cognitive; Cognitive Therapy; Collaborations; Cues; Data; Disease; Double-Blind Method; Economic Burden; Ethanol; Exposure to; Extinction (Psychology); Fright; Functional Magnetic Resonance Imaging; General Population; Health Expenditures; Human; Individual; Intervention; Investigation; Knowledge; Measures; Mental Health; Mission; Morbidity - disease rate; Motivation; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neuropeptides; Oxytocin; Participant; Patient Care; Patient Self-Report; Pharmacological Treatment; Pharmacotherapy; Pilot Projects; Placebos; Post-Traumatic Stress Disorders; Prevalence; Psychotherapy; Public Health; Randomized; Randomized Controlled Trials; Research; Research Design; Risk; Science; Self Administration; Standardization; Strategic Planning; Substance Use Disorder; Symptoms; Techniques; Testing; Therapeutic Intervention; Time; TimeLine; Translating; Trauma; Treatment outcome; Trust; Veterans; Withdrawal Symptom; alcohol behavior; alcohol response; alcohol use disorder; associated symptom; base; blood oxygen level dependent; care outcomes; clinical outcome measures; clinical practice; comorbidity; craving; disability; effective therapy; efficacy evaluation; evidence base; health care service utilization; improved; improved outcome; innovation; insight; military veteran; mortality; multidisciplinary; neurobiological mechanism; neuroimaging; novel; physical conditioning; placebo controlled study; preclinical study; psychosocial; reduce symptoms; reduced alcohol use; response; social cognition; treatment effect; treatment optimization

PROJECT SUMMARY/ABSTRACT Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur and are associated with significant morbidity, mortality, and health care expenditures. Military Veterans are at increased risk for co- occurring AUD and PTSD, with prevalence rates 2-4 times higher than the general population. Our group developed an integrated intervention entitled Concurrent Treatment of PTSD and Substance Use Disorders using Prolonged Exposure (COPE). COPE incorporates empirically validated cognitive-behavioral techniques for AUD with Prolonged Exposure (PE) therapy for PTSD. Several randomized controlled trials among Veterans and civilians demonstrate efficacy of COPE in significantly reducing AUD and PTSD symptoms. Despite the positive findings, there remains substantial room for improving treatment outcomes and enhancing retention. Accumulating data suggest that the neuropeptide oxytocin (OT) is a promising candidate to enhance psychosocial interventions for co-occurring AUD and PTSD, as OT targets neurobiological and behavioral dysregulation common to both disorders. Preclinical and clinical studies demonstrate the ability of OT to ameliorate a variety of alcohol-related behaviors (e.g., craving, withdrawal symptoms, tolerance, ethanol self- administration), enhance fear extinction, and promote prosocial behaviors associated with successful psychosocial treatment outcomes (e.g., trust, social cognition). In a randomized controlled pilot study, our group found that OT administration prior to weekly PE therapy sessions was safe, well-tolerated, and resulted in accelerated reduction in PTSD symptoms as compared to placebo. Although the empirical and theoretical support for augmenting psychosocial interventions such as COPE with OT is robust, no studies to date have examined this combined approach. The primary objective of the proposed Stage II study is to examine the efficacy of OT as compared to placebo in reducing (1) alcohol use, and (2) PTSD symptoms among Veterans receiving COPE therapy. To accomplish this, we will employ a manualized, evidence-based, cognitive-behavioral intervention (COPE); a randomized, double-blind, placebo-controlled study design; standardized, repeated dependent measures of clinical outcomes at multiple time points; and we will leverage close collaboration with well-established VA clinics prepared to efficiently translate positive findings into practice. In addition, to evaluate purported neurobiological mechanisms of change, we will employ functional magnetic resonance imaging (fMRI) at pre- and post-treatment and examine AUD biomarkers. The proposed study directly addresses the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in that it aims to identify pharmacologic treatments to address co-occurring AUD and PTSD simultaneously. The findings from this study will provide new information and mechanistic insights to directly inform clinical practice and accelerate the research in this highly understudied area.

项目总结/文摘