Feasibility Study To Prevent Post-ICU Depression

描述(申请人提供)：28%的需要机械通气超过2天的患者在两个月内发展为新的抑郁障碍。预防抑郁症可能会改善大约50万美国人的健康、康复和生活质量，这些人每年在呼吸衰竭和长时间的机械通气中幸存下来。在人类研究和类似的动物模型中，如果在炎症或环境应激期间给予抗抑郁药物，抑郁症可以得到实质性预防。这导致了我们的假设，即抑郁症可以通过对急性呼吸衰竭患者早期使用SSRI药物来预防，从而加速他们恢复可能的最佳功能。然而，在危重病人身上进行大型、多中心抑郁症预防试验的障碍是显著的。进行一项规模较小的可行性研究是合乎逻辑的第一步。因此，由一位在危重护理医学和精神病学方面有研究经验的新研究人员修订R34应用的目的是建立一项大规模随机试验的可行性，以便在急性呼吸衰竭病程的非常早期给患者使用艾司西普兰。建议进行一项随机、双盲、安慰剂对照、单部位一级预防试验，并计划剂量递增，以确定是否可行：快速确定符合条件的受试者；从代理人那里获得高比例的同意(60%)；招募100名受试者；在2年内接受至少80%的计划剂量；进行90%的8周随访并成功掩盖有效用药分配。这项试验还将确定拒绝重新同意、使用非协议抗抑郁药或出现抗抑郁药停药症状的受试者的比例。医疗不良事件和自杀意念率将被记录下来。虽然适度的样本量排除了对试验组之间抑郁评分或不良事件发生率差异的确定性假设检验，但这些数据将被用于估计设计参数，并为随后的有效性试验选择主要的抑郁测量。这项申请响应了NIMH PAR-06-248《从干预发展到服务：探索性研究拨款》，并解决了NIMH情绪障碍研究战略计划中的两个优先领域。跨学科研究团队包括一名重症监护临床医生和研究员、精神病学家、生物伦理学家、研究主题倡导者和一名临床试验人员。

DESCRIPTION (provided by applicant): Twenty-eight percent of patients that require mechanical ventilation for more than 2 days develop a new depressive disorder within two months. Preventing depression would likely improve the health, rehabilitation and quality of life for the approximately half-million Americans that annually survive respiratory failure and prolonged mechanical ventilation. In human studies and analogous animal models, depression can be substantially prevented if antidepressant medications are given during the period of inflammatory or environmental stress. This leads to our hypothesis that depression can be prevented by early administration of SSRI medications to patients with acute respiratory failure thereby accelerating their return to best possible function. However, the barriers to conducting a large, multi-center depression prevention trial in critically ill humans are significant. Conducting a smaller feasibility study is a logical first step. Therefore, the objective of this revised R34 application by a new investigator with research experience in critical care medicine and psychiatry is to establish the feasibility of conducting a large-scale randomized trial to administer escitalopram to patients very early in the course of acute respiratory failure. A randomized, double-blind, placebo-controlled, single-site primary prevention trial with a scheduled dose escalation is proposed to determine if it is feasible to rapidly identify eligible subjects; obtain a high proportion of consent (> 60%) from proxies; enroll 100 subjects over 2 years; administer at least 80% of planned doses; have > 90% 8 week follow-up and successfully mask active medication assignment. The trial will also determine the proportion of subjects that decline re-consent, use off-protocol antidepressants or develop antidepressant withdrawal symptoms. Medical adverse event and suicidal ideation rates will be recorded. While the modest sample size precludes definitive hypothesis testing of differences in depression scores or adverse event rates between the experimental arms, these data will be used to estimate design parameters and to select a primary depression measure for a subsequent effectiveness trial. This application is responsive to NIMH PAR-06-248 From Intervention Development to Services: Exploratory Research Grants and addresses two priority areas in the NIMH Strategic Plan on Mood Disorders Research. The interdisciplinary research team includes a critical care clinician and researcher, psychiatrist, bioethicist, research subject advocate and a clinical trialist.