Targeting sleep homeostasis to improve alcohol use disorder treatment outcomes

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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.