Enhancing Prolonged Exposure Therapy for PTSD with Oxytocin

使用催产素增强 PTSD 的长期暴露疗法

• 批准号: 9890048
• 负责人: JULIANNE Christina Flanagan
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9890048
• 关键词: Address; Adherence; Affect; Aggressive behavior; Animals; Anti-Anxiety Agents; Anxiety; Area; Attenuated; Behavior; Chronic; Chronic Disease; Clinical; Clinical Research; Cognitive Therapy; Country; Data; Depression and Suicide; Diagnostic; Disease remission; Dose; Double-Blind Method; Dropout; Drops; Economic Burden; Evidence based treatment; Exposure to; Family; Feeling suicidal; Fright; Functional disorder; Goals; Gold; Health; Health Care Costs; Health Expenditures; Healthcare; Human; Impairment; Individual; Interpersonal Violence; Intervention; Investigation; Investments; Knowledge; Maintenance; Measurement; Measures; Mental Depression; Mental Health; Mental Health Services; Mental disorders; Military Personnel; Mission; Modeling; Morbidity - disease rate; Neurobiology; Neuropeptides; Occupational; Outcome; Oxytocin; Participant; Patient Care; Patient Dropouts; Patient Self-Report; Patients; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Pilot Projects; Placebos; Post-Traumatic Stress Disorders; Prognostic Marker; Public Health; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Research; Risk; Safety; Science; Severities; Site; Sleep; Standardization; Stress; Substance abuse problem; Symptoms; Time; Training; Treatment outcome; Trust; Veterans; adherence rate; brain circuitry; comorbid depression; depressive symptoms; design; disability; double-blind placebo controlled trial; effective therapy; efficacy testing; evidence base; experience; follow-up; health administration; health care service utilization; improved; improved outcome; learning extinction; mortality; multidisciplinary; neurobiological mechanism; neuroimaging; neuropsychiatry; phase 2 study; physical conditioning; pre-clinical research; premature; psychosocial; reduce symptoms; research and development; retention rate; social; social cognition; standard care; symptomatic improvement; symptomatology; treatment response; treatment services

Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. PTSD is a chronic disorder that is associated with significant morbidity, mortality, disability, and costly health care expenditures. The clinical impairment associated with PTSD among Veterans is severe and associated with comorbid depression, suicidality, substance abuse, physical health problems, interpersonal violence, and neuropsychiatric impairment. Despite these pervasive health consequences, the current treatment services offered to Veterans do not adequately address PTSD. Several promising psychosocial interventions, including Prolonged Exposure (PE) therapy, have been developed for the treatment of PTSD. Although PE is one of the most widely used evidence-based treatments for PTSD, there is substantial room for improvement in outcomes and retention rates. For example, approximately one-third of patients dropout of PE treatment prematurely, and the highest dropout rates occur among Veterans. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, identifying pharmacotherapies to enhance PTSD treatment retention and outcomes is critical. Accumulating data from our group and others suggests that oxytocin is a promising candidate to achieve this goal. Oxytocin is known to promote prosocial behaviors associated with successful psychosocial treatment outcomes (e.g., trust, safety, social cognition) and has demonstrated positive effects on extinction learning in animal and human stress models. Furthermore, recent neuroimaging studies show that oxytocin has the ability to ameliorate dysregulation of the corticolimbic brain circuitry, which is a central component of the pathophysiology and maintenance of PTSD. In the only study to date examining the feasibility, acceptability, and preliminary efficacy of augmenting PE with oxytocin, our group found that participants randomized to the oxytocin condition demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores compared to participants randomized to the placebo condition. Therefore, the primary objective of the proposed two-site Phase II study is to examine the ability of oxytocin (vs. placebo) combined with PE therapy to (1) reduce PTSD symptom severity, (2) improve rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, we will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6 month follow-up). The proposed study directly addresses the mission of the Veterans Health Administration Blueprint for Excellence in that it seeks to advance personalized and proactive mental health care opportunities for Veterans. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the neurobiological mechanisms underlying PTSD and positive treatment response.

创伤后应激障碍（PTSD）是美国最普遍的心理健康障碍 退伍军人。 PTSD是一种慢性疾病，与明显的发病率，死亡率， 残疾和昂贵的医疗支出。退伍军人中与PTSD相关的临床障碍 严重，与合并抑郁，自杀，药物滥用，身体健康有关 问题，人际暴力和神经精神障碍。尽管有这些普遍的健康 后果，提供给退伍军人的当前治疗服务不能充分解决PTSD。 几种有希望的社会心理干预措施，包括长时间暴露（PE）治疗，已经是 开发用于治疗PTSD。尽管PE是使用最广泛的证据之一 PTSD的治疗方法，有很大的改善结果和保留率的空间。例如， 大约有三分之一的患者过早地辍学，并且辍学率最高 在退伍军人中。与VA研发办公室一致，以发展有效 PTSD治疗，鉴定药物疗法以增强PTSD治疗保留和结果是 批判的。从我们小组和其他人中积累数据表明催产素是有前途的候选人 实现这一目标。催产素已知可以促进与成功相关的亲社会行为 社会心理治疗结果（例如信任，安全，社会认知），并表现出积极的影响 关于动物和人类压力模型的灭绝学习。此外，最近的神经影像学研究表明 催产素的能力可以改善皮质唇脑电路的失调，这是一个中央 PTSD的病理生理学和维持的成分。在迄今唯一的研究中 使用催产素增强PE的可行性，可接受性和初步功效，我们的小组发现 随机分配到催产素状况的参与者表现出较低的PTSD和抑郁症状 在PE期间，与随机分配到安慰剂的参与者相比，工作联盟分数更高 健康）状况。因此，提出的两点II期研究的主要目标是检查 催产素（vs.安慰剂）与PE疗法结合到（1）减轻PTSD症状严重程度，（2）改善 PTSD症状的改善率，以及（3）提高PE依从性和保留率。到 实现这些目标，我们将采用随机，双盲，安慰剂对照试验并使用 标准化的，重复的依赖性量度在五个时间点（基线，中间处理，末端） 治疗以及3个月的随访）。拟议的研究直接解决了退伍军人的任务 健康管理局蓝图卓越的蓝图，它试图推动个性化和积极主动的精神 退伍军人的医疗保健机会。这项研究的发现将提供有关有关的关键新信息 催产素对PTSD的社会心理治疗的功效，以及有关 PTSD和阳性治疗反应的神经生物学机制。