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一个可预防的主要原因。 存在基于证据的治疗方法，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。禁欲期间失眠 在成人 AUD 患者中，该疾病非常普遍、持续且独立预测复发。试点随机化 我们小组和其他人的对照试验表明，失眠认知行为治疗 (CBTi) 可以改善睡眠和白天 AUD 患者出现失眠症状，但其对饮酒的影响尚未得到充分测试。 此外，尽管已确定失眠与复发之间存在关联，但潜在的睡眠机制 人们对这种关系知之甚少。先前的工作已发现候选人存在显着异常 成人 AUD 患者的机制是睡眠稳态，这是一个关键的睡眠调节系统，反映了 “睡眠驾驶。”因此，该项目的目标是评估 (a) CBTi 对睡眠的益处， 饮酒和相关的白天症状以及 (b) CBTi 对稳态睡眠系统的影响和 它与成人 AUD 治疗失眠的临床结果相关。一百五十个成年人 因失眠而进入密歇根大学成瘾治疗服务的 AUD 治疗将 招募并随机接受为期 6 周的远程医疗 CBTi (CBTi-TM，n=75) 或睡眠卫生治疗 教育程度（SHE-TM，n=75）。将在治疗前和治疗后评估饮酒、睡眠和日间症状结果 治疗以及 3、6 和 12 个月的随访。客观多导睡眠图将在之前和之后进行 评估稳态睡眠驱动力的治疗。研究的具体目的是：（1）确定是否 在接受 AUD 治疗的成人中，CBTi-TM 比 SHE-TM 更能改善失眠和白天症状 失眠； (2)比较CBTi-TM与SHE-TM对酒精复吸的疗效；和（3）比较 CBTi-TM 到 SHE-TM 对稳态睡眠驱动的影响。次要目标将评估在多大程度上 酒精使用的变化是由 CBTi-TM（相对于 SHE-TM）对体内平衡的影响的变化介导的 睡眠系统。该试验的结果对患有此病的患者的未来治疗具有重要意义 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.