Hypnotics and the Treatment of Psychiatric Disorders

描述(申请人提供)：慢性失眠是严重抑郁发作(MDE)期间最常见的症状之一，失眠症状独立地预示着生活质量(QOL)差、自杀风险增加以及MDE复发风险增加。相比之下，初步证据表明，在MDE期间治疗失眠可以减少白天的症状负担，提高生活质量。催眠药(安眠药)比其他任何疾病更常用于治疗精神问题，这并不令人惊讶，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，可能需要在服用抗抑郁药的同时开催眠药。然而，人们对联合使用最常用的抗抑郁药和催眠药的有效性和安全性知之甚少。这一探索性/发展性赠款(R34机制)将用于MDE相关失眠的治疗，将支持为感兴趣的拟议结果开发数据收集方法，并将测试招募和留住参与者的可行性，并应提供对失眠抑郁患者在抗抑郁药中添加催眠药的效果大小的估计。具体地说，对开放氟西汀单一治疗2周有反应的MDE和失眠患者被随机分为安慰剂或催眠药唑吡坦4周，同时继续开放氟西汀。参与者将在催眠/安慰剂治疗后再接受4个月的自然主义随访。重要的结果测量应包括报告和PSG睡眠、情绪、自杀念头和生活质量。我们假设，与接受氟西汀和安慰剂治疗相比，联合使用唑吡坦和氟西汀会带来更好的生活质量。预测的效果大小表明，在这一探索性/发展赠款期间可以招募的群体之间很可能在统计上存在显著差异。该应用程序将导致检验催眠药物在抑郁症失眠症患者中的有效性的有效方法，并应为随后的R01应用程序产生现实的样本量预测，其中可能包括安慰剂、安眠药和镇静抗抑郁剂作为抑郁症合并失眠的附加疗法的三臂比较。

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.