1/3-Reducing Suicial Ideation Through Insomnia Treatment (REST-IT)

描述（由申请人提供）：数十份流行病学报告将失眠与重度抑郁症患者自杀意念、自杀行为和自杀死亡的风险增加联系起来。失眠增加自杀意念强度的机制可能是通过对睡眠的功能失调的信念和态度来介导的，有点类似于绝望。我们有未发表的初步数据显示，与安慰剂加氟西汀相比，在开放标签氟西汀治疗抑郁性失眠症患者时，催眠药右佐匹克隆加氟西汀与自杀意念减少相关。我们现在建议在一项多中心临床试验中证实失眠治疗减少自杀意念的前提。维克森林大学（WFU）将作为协调网站和招聘网站，而杜克大学（DU）和威斯康星州大学（UW）也将作为招聘网站。患有重度抑郁症、失眠症和轻度-中度自杀意念的门诊患者（N=138）将接受开放标签氟西汀治疗8周，并将在同一时期进一步随机分配至睡前接受右佐匹克隆或安慰剂。患者将在治疗开始后第1、2、4、6和8周进行回访。评估将包括自杀意念强度、总体抑郁严重程度、失眠严重程度、对睡眠的功能障碍性认知、噩梦强度、绝望和活动记录。所有数据都将输入WF创建的基于网络的界面，并通过研究中心之间的定期电话会议确保研究中心之间方法的一致性。样本量将足以使80%的把握度检测到治疗组之间Beck自杀意念量表的2.0分差异。 将通过以下方式确保受试者的安全性：（1）排除基线时有严重以上自杀意念的患者，（2）频繁随访，（3）限制催眠药的使用，（4）在精神病紧急情况下进入大学精神病住院部，（5）通过研究中心各自的精神病住院计划提供每天24小时的紧急服务，（6）家庭和亲人的参与，如果可以的话，在同意过程中，（7）和创建一个数据安全监测委员会，将包括抑郁症，失眠，临床试验，统计学，自杀学，生物统计学， 伦理道德和病人的辩护律师主要目的是评估催眠药物治疗失眠对自杀意念强度的影响。第二个目的是测试抑郁失眠症患者自杀意念的减少是否是通过减少对睡眠的功能失调信念、减少绝望感或减少噩梦来介导的。这项研究的结果将为轻度-中度自杀意念、失眠和抑郁患者的适当管理提供信息-这是一种非常常见的临床情况。 公共卫生相关性：失眠是抑郁症的常见症状，失眠与自杀意念、自杀行为和自杀死亡有着令人信服的联系。这项研究将探讨是否谨慎，明智地使用催眠药将减少自杀意念的抑郁失眠症患者谁已经接受抗抑郁治疗。

DESCRIPTION (provided by applicant): Dozens of epidemiologic reports have linked insomnia to increased risk for suicidal ideation, suicidal behavior and suicide death in patients with major depression. The mechanism whereby insomnia increases the intensity of suicidal ideation may be mediated through dysfunctional beliefs and attitudes about sleep, somewhat similar to hopelessness. We have unpublished, preliminary data showing that the addition of the hypnotic eszopiclone to open-label fluoxetine in the treatment of depressed insomniacs is associated with a reduction in suicidal ideation, as compared with placebo added to fluoxetine. We now propose to confirm the premise that treatment of insomnia reduces suicidal ideation in a multi-site clinical trial. Wake Forest University (WFU) will be the coordinating site and a recruitment site, while Duke University (DU) and University of Wisconsin (UW) will also serve as recruiting sites. Outpatients (N=138) with major depression, insomnia, and mild- moderate suicidal ideation will be treated with open label fluoxetine for 8 weeks and will be further randomized to receive either eszopiclone or placebo at bedtime for the same period. Patients will have return office visits at 1, 2, 4, 6, and 8 weeks after treatment initiation. Assessments wll include measures of suicidal ideation intensity, overall depression severity, insomnia severity, dysfunctional cognitions about sleep, nightmare intensity, hopelessness, and actigraphy. All data will be entered in a WF-created web-based interface, and consistency of methodology across sites will be assured with regular teleconferences between sites. The sample size will be sufficient to allow 80% power to detect a 2.0 point difference in the Beck Scale for Suicide Ideation between treatment arms. Safety of participants will be assured by (1) exclusion of patients with more than severe suicidal ideation at baseline, (2) frequent follow up, (3) limited access to hypnotics, (4) access to university psychiatric inpatients units for psychiatric emergencies, (5) 24-hour per day emergency services available through the sites respective psychiatric residency programs, (6) involvement of families and loved ones, when available, in the consent process, (7) and the creation of a Data Safety Monitoring Committee that will include expertise in depression, insomnia, clinical trials, statistics, suicidology, biostatistics, ethics, and a patient advocate. The primary aim will be to assess the effect of treating insomnia with hypnotic medication on the intensity of suicidal ideation. The secondary aim will be to test whether reductions in suicidal ideation in depressed insomniacs is mediated through either reduced dysfunctional beliefs about sleep, reduced hopelessness, or through reduction in nightmares. The results of this study will inform the appropriate management of patients with mild-moderate suicidal ideation, insomnia and depression - representing an extremely common clinical scenario. PUBLIC HEALTH RELEVANCE: Insomnia is a common symptom of depression, and insomnia has been convincingly linked to suicidal ideation, suicidal behavior, and suicide death. This study will address whether cautious, judicious use of hypnotics will reduce suicidal ideation in depressed insomniacs who are already receiving antidepressant treatment.