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: 10417039
• 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/10417039
• 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; Human; Impairment; Individual; Interpersonal Violence; Intervention; Investigation; Investments; Knowledge; Maintenance; Measurement; Measures; Mental Depression; Mental Health; Mental Health Services; Mental disorders; 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; Placebo Control; Placebos; Post-Traumatic Stress Disorders; 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; Veterans Health Administration; adherence rate; brain circuitry; comorbid depression; depressive symptoms; design; disability; double-blind placebo controlled trial; effective therapy; efficacy evaluation; efficacy testing; evidence base; experience; follow-up; health care service utilization; improved; improved outcome; learning extinction; military veteran; mortality; multidisciplinary; neurobiological mechanism; neuroimaging; neuropsychiatry; phase 2 study; physical conditioning; pre-clinical research; premature; prognostic indicator; 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）是美国最普遍的精神健康障碍。 退伍军人。 PTSD 是一种慢性疾病，与显着的发病率、死亡率、 残疾和昂贵的医疗保健支出。退伍军人中与 PTSD 相关的临床损害 病情严重，并与共病抑郁症、自杀倾向、药物滥用、身体健康有关 问题、人际暴力和神经精神障碍。尽管这些普遍的健康 后果是，目前向退伍军人提供的治疗服务并不能充分解决创伤后应激障碍。 一些有前景的心理社会干预措施，包括长期暴露（PE）疗法，已被 开发用于治疗 PTSD。尽管 PE 是使用最广泛的循证方法之一 PTSD 的治疗，在结果和保留率方面还有很大的改善空间。例如， 大约三分之一的患者过早退出体育治疗，并且退出率最高 在退伍军人中。与 VA 研究与开发办公室的倡议一致，以开发有效的 PTSD 的治疗方法，确定药物疗法以增强 PTSD 治疗的保留和结果是 批判的。我们小组和其他人积累的数据表明，催产素是一种有希望的候选药物。 实现这一目标。众所周知，催产素可以促进与成功相关的亲社会行为。 心理社会治疗结果（例如信任、安全、社会认知）并已显示出积极效果 关于动物和人类压力模型中的灭绝学习。此外，最近的神经影像学研究表明 催产素能够改善皮质边缘大脑回路的失调，该回路是大脑的中枢。 PTSD 的病理生理学和维持的组成部分。迄今为止唯一一项研究 通过催产素增强 PE 的可行性、可接受性和初步疗效，我们小组发现： 随机接受催产素条件的参与者表现出较低的创伤后应激障碍和抑郁症状 在体育运动期间，与随机接受安慰剂的参与者相比，工作联盟得分更高 健康）状况。因此，拟议的两地二期研究的主要目标是检验 催产素（相对于安慰剂）联合 PE 治疗可 (1) 减轻 PTSD 症状的严重程度，(2) 改善 PTSD 症状改善率，(3) 提高体育锻炼依从性和保留率。到 为了实现这些目标，我们将采用随机、双盲、安慰剂对照试验并使用 五个时间点（基线、治疗中期、治疗结束）的标准化、重复依赖性变化测量 治疗以及 3 个月和 6 个月的随访）。拟议的研究直接涉及退伍军人的使命 健康管理卓越蓝图，旨在促进个性化和主动的心理 退伍军人的医疗保健机会。这项研究的结果将提供有关以下方面的重要新信息： 催产素增强 PTSD 心理社会治疗的功效，以及有关 PTSD 和积极治疗反应背后的神经生物学机制。