Ray Lara A, Baskerville Wave-Ananda, Nieto Steven J, Grodin Erica, Enders Craig, Kady Annabel, Meredith Lindsay, Gillis Artha, Leventhal Adam, Ho Diana, Miotto Karen
Department of Psychology, University of California at Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA.
Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA, USA.
Psychopharmacology (Berl). 2024 Mar;241(3):543-553. doi: 10.1007/s00213-023-06504-6. Epub 2023 Nov 28.
Screening novel medications for alcohol use disorder (AUD) requires models that are both efficient and ecologically-valid. Ideally, such models would be associated with the outcomes of a given medication in clinical trials.
To test a novel human laboratory model in which individuals with intrinsic motivation to change their drinking engage in a "practice quit" attempt consisting of 6 days of complete abstinence from alcohol.
Individuals with current AUD completed a randomized, double-blind, placebo-controlled study of naltrexone (50 mg), varenicline (2 mg bid), or matched placebo. Participants were titrated onto the study medication for 1 week prior to starting the 6-day practice quit attempt. During the practice quit attempt, participants completed daily interviews with research staff. All participants completed an alcohol cue-exposure paradigm before starting the study medication and after 2 weeks of study medication.
There were no significant medication effect on drinks per drinking day (F(2,49) = 0.66, p = 0.52) or percent days abstinent (F(2,49) = 0.14, p = 0.87) during the 6-day practice quit period. There were no medication effects on alcohol cue-reactivity (F(2,44) = 0.80, p = 0.46). Notably, participants sharply reduced their drinking during the entire 13-day medication treatment period, as compared to reducing only during the 6-day practice quit period. During the total medication period, higher levels of motivation to change was associated with higher percent days abstinent (F(1,49) = 8.12, p < 0.01).
This study reports mostly null findings, which challenges us to decompose its nuanced design to consider model refinements. Possible changes to the model include considering the requirement for intrinsic motivation for change, including a longer practice quit period, encompassing the medication administration timeframe in the practice quit period, increasing the required sample size for signal detection, and examining a post COVID-19 pandemic cohort.
筛选用于酒精使用障碍（AUD）的新型药物需要高效且具有生态效度的模型。理想情况下，此类模型应与给定药物在临床试验中的结果相关联。
测试一种新型人体实验室模型，即有内在动机改变饮酒习惯的个体进行为期6天完全戒酒的“尝试戒酒”。
当前患有酒精使用障碍的个体完成了一项关于纳曲酮（50毫克）、伐尼克兰（2毫克，每日两次）或匹配安慰剂的随机、双盲、安慰剂对照研究。在开始为期6天的尝试戒酒之前，参与者先服用研究药物1周进行滴定。在尝试戒酒期间，参与者每天与研究人员进行访谈。所有参与者在开始研究药物治疗前和治疗2周后均完成了酒精线索暴露范式。
在为期6天的尝试戒酒期间，药物对每日饮酒量（F(2,49) = 0.66，p = 0.52）或戒酒天数百分比（F(2,49) = 0.14，p = 0.87）无显著影响。药物对酒精线索反应性也无影响（F(2,44) = 0.80，p = 0.46）。值得注意的是，与仅在6天尝试戒酒期间减少饮酒相比，参与者在整个13天的药物治疗期间饮酒量大幅减少。在整个药物治疗期间，更高的改变动机水平与更高的戒酒天数百分比相关（F(1,49) = 8.12，p < 0.01）。
本研究大多报告了无显著结果，这促使我们剖析其细微的设计，以考虑模型的改进。模型可能的改变包括考虑改变的内在动机要求，包括更长的尝试戒酒期，将药物给药时间范围纳入尝试戒酒期，增加信号检测所需的样本量，以及研究新冠疫情后的队列。
