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调节的，有点类似于绝望。我们有未发表的初步数据显示，在开放标签氟西汀治疗抑郁症失眠症时，与在氟西汀中添加安慰剂相比，在氟西汀中添加催眠药物艾索匹克隆与减少自杀意念有关。我们现在建议在多地点临床试验中确认治疗失眠减少自杀意念的前提。维克森林大学（WFU）将作为协调地点和招聘地点，杜克大学（DU）和威斯康星大学（UW）也将作为招聘地点。有重度抑郁、失眠和轻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，并在同一时间段内随机接受艾司佐匹克隆或安慰剂。患者将在治疗开始后1、2、4、6和8周回访。评估包括自杀意念强度、整体抑郁严重程度、失眠严重程度、睡眠功能失调认知、噩梦强度、绝望感和活动记录仪。所有数据将输入世界自然基金会创建的基于网络的界面，并通过各站点之间的定期电话会议确保各站点方法的一致性。样本量将足以允许80%的功率来检测治疗组之间贝克自杀意念量表2.0点的差异。参与者的安全将通过以下方式得到保证：(1)在基线时排除有严重自杀意念的患者，(2)频繁随访，(3)限制使用催眠药，(4)大学精神科住院病房的精神紧急情况，(5)每天24小时的紧急服务，通过网站各自的精神科住院医师计划，(6)在同意过程中，如果有的话，让家人和亲人参与。(7)成立数据安全监测委员会，该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、

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 We have unpublished, preliminary data showing that the addition of the hypnotic eszopiclone to open-label fluoxetine in the treatment of depressed insomniacs is associated with a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.