Targeting sleep homeostasis to improve alcohol use disorder treatment outcomes

摘要 酒精使用障碍（AUD）是美国发病率和死亡率的主要可预防原因。 循证治疗是存在的，但成年AUD患者的复发率仍然高得令人无法接受。小说 因此，迫切需要以复发的已知预测因子为目标的方法。禁欲期间的冲动 在成人AUD患者中是高度流行的、持续的，并且是复发的独立预测因素。初步随机化 我们小组和其他人的对照试验表明，失眠症的CBT（CBTi）改善了睡眠和白天 它在AUD和失眠患者中的症状，但它对饮酒的影响尚未得到充分的测试。 此外，尽管失眠和复发之间的联系已经确定，但潜在的睡眠机制， 人们对这种关系知之甚少。先前的工作已经确定了候选人的显着异常 在成年AUD患者中，睡眠稳态是一种关键的睡眠调节系统， “睡眠驾驶”因此，本项目的目标是评估（a）CBTi对睡眠的益处， 饮酒和相关的日间症状，以及（B）CBTi对稳态睡眠系统的影响， 其与成人AUD治疗失眠的临床结局的相关性。一百五十个成人 在密歇根大学成瘾治疗服务中心接受AUD治疗， 招募并随机分配至6周的远程医疗CBTi（CBTi-TM，n=75）或睡眠卫生 教育（SHE-TM，n=75）。饮酒、睡眠和日间症状的结果将在治疗前和治疗后进行评估。 治疗以及3个月、6个月和12个月随访时。客观多导睡眠图将在术前和术后进行 治疗以评估稳态睡眠驱动。研究的具体目的是：（1）确定是否 在AUD治疗中，CBTi-TM比SHE-TM更能改善成人的失眠和日间症状， 失眠;（2）比较CBTi-TM与SHE-TM对酒精复发的疗效;（3）比较 CBTi-TM到SHE-TM对稳态睡眠驱动的影响。次要目标将评估 酒精使用的变化是由CBTi-TM（与SHE-TM）对体内平衡的影响的变化介导的。 睡眠系统这项试验的结果对未来治疗患有 澳元支持继续禁欲。

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.