Targeting sleep homeostasis to improve alcohol use disorder treatment outcomes

摘要 在美国，酒精使用障碍(AUD)是导致发病率和死亡率的主要可预防原因。 循证治疗是存在的，但成人AUD的复发率仍然高得令人无法接受。小说 因此，迫切需要针对已知的复发预测因素的方法。禁欲期间的失眠 在成人AUD患者中高度流行、持续，并且独立地预测复发。飞行员随机化 由我们小组和其他人进行的对照试验表明，CBT治疗失眠(CBTi)可以改善睡眠和白天 AUD和失眠患者的症状有所改善，但其对饮酒的影响尚未得到充分测试。 此外，尽管失眠和复发之间存在联系，但潜在的睡眠机制 人们对这种关系知之甚少。先前的工作发现了一名候选人的显著异常 成人AUD的发病机制，睡眠动态平衡是反映睡眠调节系统的关键 “睡眠驱动力。”因此，该项目的目标是评估(A)CBTi对睡眠的益处， 饮酒和相关的日间症状以及(B)CBTi对体内平衡睡眠系统和 它与成人AUD伴失眠治疗的临床结果相关。150个成年人 在密歇根大学成瘾治疗服务中心接受AUD治疗的失眠症患者将被 招募并随机接受远程医疗提供的CBTi(CBTi-TM，n=75)或睡眠卫生6周 教育(SHE-TM，n=75)。饮酒、睡眠和白天症状结果将在治疗前和治疗后进行评估 治疗后3个月、6个月、12个月随访。客观多导睡眠监测将在前后进行。 评估体内平衡睡眠驱动力的治疗。这项研究的具体目的是：(1)确定 CBTI-TM在AUD治疗中对成人失眠和日间症状的改善作用优于SHE-TM (2)比较CBTi-TM和SHE-TM对酒精复吸的疗效；(3)比较 CBTi-TM与SHE-TM对稳态睡眠驱动力的影响次级目标将评估在多大程度上 酒精使用的变化是通过CBTi-TM(vs SHE-TM)对体内平衡的影响来调节的 睡眠系统。这项试验的发现对未来的治疗具有重要的意义。 以支持持续的禁欲。

ABSTRACT Alcohol use disorder (AUD) is a leading preventable cause of morbidity and mortality in the United States. Evidence-based treatments exist, but relapse rates among adults with AUD remain unacceptably high. Novel approaches that target known predictors of relapse are therefore urgently needed. Insomnia during abstinence is highly prevalent, persistent, and independently predicts relapse in adults with AUD. Pilot randomized controlled trials by our group and others have shown that CBT for insomnia (CBTi) improves sleep and daytime symptoms among patients with AUD and insomnia, but its impact on drinking has not been adequately tested. Moreover, despite the identified associations between insomnia and relapse, the sleep mechanisms underlying this relationship are poorly understood. Prior work has identified significant abnormalities in a candidate mechanism among adults with AUD, sleep homeostasis, which is a key sleep regulatory system reflecting “sleep drive.” The objectives of this project, therefore, are to evaluate (a) the benefits of CBTi for sleep, drinking, and associated daytime symptoms and (b) the effects of CBTi on the homeostatic sleep system and its association with clinical outcomes in adults in AUD treatment with insomnia. One hundred and fifty adults entering AUD treatment at the University of Michigan Addiction Treatment Services with insomnia will be recruited and randomized to 6 weeks of either telemedicine-delivered CBTi (CBTi-TM, n=75) or Sleep Hygiene Education (SHE-TM, n=75). Drinking, sleep, and daytime symptom outcomes will be assessed pre- and post- treatment and at 3-, 6- and 12-month follow-up. Objective polysomnography will be conducted before and after treatment to assess homeostatic sleep drive. The specific aims of the study are: (1) to determine whether CBTi-TM improves insomnia and daytime symptoms more than SHE-TM in adults in AUD treatment with insomnia; (2) to compare the efficacy of CBTi-TM to SHE-TM on alcohol relapse; and (3) to compare the effects of CBTi-TM to SHE-TM on homeostatic sleep drive. Secondary aims will assess the extent to which changes in alcohol use are mediated by changes in the CBTi-TM (vs. SHE-TM) effects on the homeostatic sleep system. The findings from this trial have important implications for the future treatment of patients with AUD to support continued abstinence.