Yale Stress Center (Sinha, Wemm, Fogelman, Milivojevic, Hermes), Department of Psychiatry (Sinha, Wemm, Fogelman, Milivojevic, Morgan, Angarita, Hermes), and Department of Neuroscience (Sinha), Yale University School of Medicine, New Haven, Conn.; Department of Psychiatry, Stony Brook University School of Medicine, Stony Brook, N.Y. (Fox).
Am J Psychiatry. 2021 May 1;178(5):447-458. doi: 10.1176/appi.ajp.2020.20050609. Epub 2020 Nov 19.
Alcohol use disorder (AUD) is a leading cause of global disease burden. Chronic, heavy use increases the likelihood of alcohol withdrawal symptoms and associated secondary outcomes of alcohol craving and mood, anxiety, and sleep disturbances, which are predictive of poor treatment outcomes. The authors examined whether alcohol withdrawal symptoms moderate the efficacy of prazosin in reducing alcohol intake and associated secondary outcomes.
A 12-week, double-blind, randomized, controlled proof-of-concept trial of prazosin (16 mg/day, with a 2-week titration) was conducted in community-recruited adults with current alcohol dependence (N=100) with varying levels of alcohol withdrawal symptoms assessed at treatment entry. Primary outcomes were daily self-reported drinking days and heavy drinking days, and secondary outcomes were average drinks/day and mood, anxiety, craving, and sleep quality ratings.
Modified intent-to-treat analyses indicated a significant interaction of alcohol withdrawal symptom score by treatment by full-dose treatment period (weeks 3-12) for drinking days, heavy drinking days, and average drinks/day. By week 12, participants with high alcohol withdrawal symptoms on prazosin reported 7.07% heavy drinking days and 27.46% drinking days, while those on placebo had 35.58% heavy drinking days and 58.47% drinking days (heavy drinking days: odds ratio=0.14, 95% CI=0.058, 0.333; drinking days: odds ratio=0.265, 95% CI=0.146, 0.481). No such benefit of prazosin was observed in those reporting low or no alcohol withdrawal symptoms. Individuals with high alcohol withdrawal symptoms on prazosin compared with placebo also showed significantly improved anxiety, depression, and alcohol craving over the course of the trial.
The findings indicate that alcohol withdrawal symptoms are a significant moderator of prazosin treatment response for alcohol use outcomes and for associated symptoms of alcohol craving, anxiety, and mood symptoms. These data support further evaluation of alcohol withdrawal symptoms as a prognostic indicator of prazosin's efficacy in the treatment of AUD.
酒精使用障碍（AUD）是全球疾病负担的主要原因。慢性、大量饮酒会增加出现酒精戒断症状的可能性，并伴有酒精渴求以及情绪、焦虑和睡眠障碍等相关的次要后果，这些后果预示着治疗效果不佳。作者研究了酒精戒断症状是否会影响普萘洛尔降低酒精摄入量和相关次要结果的疗效。
一项为期 12 周、双盲、随机、对照的普萘洛尔（16mg/天，为期 2 周滴定）概念验证试验，在社区招募的有当前酒精依赖的成年人中进行，他们的酒精戒断症状水平在治疗开始时进行评估。主要结果是每天自我报告的饮酒天数和重度饮酒天数，次要结果是平均每天饮酒量以及情绪、焦虑、渴求感和睡眠质量评分。
意向治疗分析表明，在治疗期间（第 3-12 周），酒精戒断症状评分与全剂量治疗期之间存在显著的交互作用，包括饮酒天数、重度饮酒天数和平均饮酒量。到第 12 周时，接受普萘洛尔治疗且酒精戒断症状评分较高的参与者报告重度饮酒天数为 7.07%，饮酒天数为 27.46%，而接受安慰剂治疗的参与者重度饮酒天数为 35.58%，饮酒天数为 58.47%（重度饮酒天数：优势比=0.14，95%CI=0.058，0.333；饮酒天数：优势比=0.265，95%CI=0.146，0.481）。在报告低水平或无酒精戒断症状的参与者中，未观察到普萘洛尔的这种益处。与安慰剂相比，接受普萘洛尔治疗且酒精戒断症状评分较高的个体在试验过程中焦虑、抑郁和酒精渴求感也显著改善。
这些发现表明，酒精戒断症状是普萘洛尔治疗酒精使用结果和相关酒精渴求、焦虑和情绪症状的重要调节因素。这些数据支持进一步评估酒精戒断症状作为普萘洛尔治疗 AUD 疗效的预后指标。
