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)是美国最常见的心理健康疾病。 退伍军人。创伤后应激障碍是一种慢性疾病，与显著的发病率、死亡率、 残疾，以及昂贵的医疗保健支出。退伍军人创伤后应激障碍相关的临床损害 病情严重，并与抑郁症、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。尽管健康无处不在 尽管如此，目前为退伍军人提供的治疗服务不足以解决创伤后应激障碍。 一些有希望的心理社会干预措施，包括长期暴露(PE)疗法，已经被 为治疗创伤后应激障碍而开发。虽然PE是目前应用最广泛的循证医学 对于创伤后应激障碍的治疗，在结果和保留率方面有很大的改善空间。例如, 大约三分之一的患者过早退出了PE治疗，而且辍学率最高 在退伍军人中。与退伍军人事务部研究和开发办公室的倡议保持一致，以开发有效的 创伤后应激障碍的治疗，确定药物疗法以增强创伤后应激障碍的治疗保留和结果 危急时刻。来自我们小组和其他人的积累数据表明，催产素是一种有希望的候选药物 实现这一目标。已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 关于动物和人类应激模型中的灭绝学习。此外，最近的神经成像研究表明 催产素有能力改善大脑皮质边缘回路的失调，这是一种中枢 创伤后应激障碍的病理生理学和维持的组成部分。在迄今为止唯一一项研究中， 在使用催产素增强PE的可行性、可接受性和初步疗效方面，我们小组发现 随机接受催产素治疗的参与者显示出较低的创伤后应激障碍和抑郁症状 在PE期间，与随机服用安慰剂的参与者相比，他们的工作联盟得分更高 条件。因此，拟议的两个地点第二阶段研究的主要目标是审查 催产素(与安慰剂相比)联合PE治疗(1)降低PTSD症状严重程度，(2)改善 创伤后应激障碍症状改善率；(3)提高PE依从率和存留率。至 为了实现这些目标，我们将采用随机、双盲、安慰剂对照的试验和使用 在五个时间点(基线、治疗中期、治疗结束)的标准化、重复依赖的变化测量 治疗、3个月和6个月随访)。拟议的研究直接涉及退伍军人的使命 健康管理的卓越蓝图，因为它寻求促进个性化和主动性心理 退伍军人的医疗保健机会。这项研究的发现将为以下方面提供关键的新信息 催产素加强创伤后应激障碍的心理社会治疗的有效性，以及关于 创伤后应激障碍和积极治疗反应的神经生物学机制。