Hypnotics and the Treatment of Psychiatric Disorders

描述（由申请人提供）：慢性失眠是重度抑郁发作（MDE）期间最常见的症状之一，失眠症状独立预测生活质量（QOL）差、自杀风险增加和MDE复发风险增加。相比之下，初步证据表明，治疗MDE期间的失眠减少了白天的症状负担，提高了生活质量。催眠药物（安眠药）比其他任何疾病都更常用于精神疾病，这并不奇怪，因为许多最新的抗抑郁药几乎没有或根本没有内在的睡眠诱导作用，可能需要沿着抗抑郁药一起开催眠药。然而，人们对最常用的抗抑郁药和催眠药联合使用的疗效和安全性知之甚少。该探索性/开发补助金（R34机制）将实施与MDE相关的失眠治疗，将支持拟定关注结局的数据收集方法的开发，并将测试招募和保留参与者的可行性，并将提供在失眠抑郁患者中添加催眠药物和抗抑郁药的效应量估计。具体而言，对开放式氟西汀单药治疗2周确有应答的MDE和失眠患者随机分配至安慰剂组或催眠药唑吡坦组4周，同时继续开放式氟西汀治疗。在催眠/安慰剂治疗后，应对受试者进行额外4个月的自然随访。重要的结局指标应包括报告和PSG睡眠、情绪、自杀想法和QOL。我们假设唑吡坦和氟西汀联合治疗的QOL优于氟西汀和安慰剂治疗。预测的效应量表明，在探索性/开发补助期间招募的组之间可能存在统计学显著差异。该申请应产生一种经过验证的方法，用于检查催眠药物在失眠抑郁症患者中的效用，并应产生后续R 01申请的实际样本量预测，其中可能包括安慰剂与催眠药和镇静抗抑郁药作为失眠抑郁症添加治疗的三组比较。

DESCRIPTION (provided by applicant): Chronic insomnia is among the most common symptoms during a major depressive episode (MDE), and the symptom of insomnia independently predicts poor quality of life (QOL), increased risk of suicide, and increased risk for recurrence of MDE. In contrast, preliminary evidence suggests that treatment of insomnia during MDE reduces the daytime symptom burden and improves QOL. Hypnotic medications (sleeping pills) are prescribed more commonly for psychiatric problems than for any other disorder, and this is not surprising since many of the newest antidepressants have little or no intrinsic sleep-inducing effect and may require that a hypnotic be prescribed along with the antidepressant. However, little is known about the efficacy and safety of combining the most commonly used antidepressant and hypnotic medications. This exploratory/development grant (R34 mechanism) will operationalize treatment of insomnia associated with MDE, will support the development of data-gathering methods for the proposed outcomes of interest, and shall test the feasibility of recruiting and retaining participants, and shall provide estimates of effect sizes for adding a hypnotic medication to an antidepressant in depressed patients with insomnia. Specifically, patients with MDE and insomnia who do respond to open fluoxetine monotherapy for 2 weeks are randomized to either placebo or the hypnotic zolpidem for 4 weeks, while continuing open fluoxetine. Participants shall be followed for an additional 4 months of naturalistic follow up after hypnotic/placebo therapy. Important outcome measures shall include reported and PSG sleep, mood, suicidal thinking, and QOL. We hypothesize that combined zolpidem and fluoxetine shall be associated with better QOL than receipt of fluoxetine and placebo. The projected effect sizes suggest that it is likely that statistically significant differences shall be found between groups that can be recruited during this exploratory/development grant. The application shall result in a proven methodology for examining the utility of hypnotic medications in depressed person with insomnia, and shall result in realistic sample size projections for a subsequent R01application that may include a three-armed comparison of placebo, versus hypnotic, versus sedating anti-depressant as add-on therapy for depression with insomnia.