Department of Psychology, University of California at Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA, 90095-1563, USA.
Center for Alcohol and Addiction Studies, Brown University School of Public Health, Providence, Rhode Island, USA.
Psychopharmacology (Berl). 2024 Aug;241(8):1679-1689. doi: 10.1007/s00213-024-06589-7. Epub 2024 Apr 13.
The alcohol cue exposure paradigm is a common method for evaluating new treatments for alcohol use disorder (AUD); however, it is unclear if medication-related reductions in cue-induced craving in the human laboratory can predict the clinical success of those medications in reducing alcohol consumption during clinical trials.
To use a novel meta-analytic approach to test whether medication effect sizes on cue-induced alcohol craving are associated with clinical efficacy in clinical trials.
We searched the literature for medications tested for AUD treatment using both the alcohol cue-reactivity paradigm and randomized clinical trials (RCTs). For alcohol cue-reactivity studies, we computed medication effect sizes for cue-induced alcohol craving (k = 36 studies, 15 medications). For RCTs, we calculated medication effect sizes for heavy drinking and abstinence (k = 139 studies, 19 medications). Using medication as the unit of analysis, we applied the Williamson-York bivariate weighted least squares estimation to account for errors in both independent and dependent variables. We also conducted leave-one-out cross validation simulations to examine the predictive utility of cue-craving medication effect sizes on RCT heavy drinking and abstinence endpoints.
There was no significant relationship between medication effects on cue-induced alcohol craving in the human laboratory and medication effects on heavy drinking ( = 0.253, SE = 0.189, p = 0.090) and abstinence ( = 0.829, SE = 0.747, p = 0.133) in RCTs.
The preliminary results of the current study challenge the assumption that alcohol cue-reactivity alone can be used as an early efficacy indicator for AUD pharmacotherapy development. These findings suggest that a wider range of early efficacy indicators and experimental paradigms be considered for Phase II testing of novel compounds.
酒精线索暴露范式是评估酒精使用障碍（AUD）新治疗方法的常用方法；然而，尚不清楚药物治疗是否能减少人类实验室中线索引起的渴望，是否能预测这些药物在临床试验中减少饮酒量的临床成功。
使用一种新的荟萃分析方法来检验药物对线索诱导的酒精渴望的影响是否与临床试验中的临床疗效相关。
我们搜索了使用酒精线索反应范式和随机临床试验（RCT）治疗 AUD 的药物的文献。对于酒精线索反应研究，我们计算了药物对线索诱导的酒精渴望的药物效应大小（k=36 项研究，15 种药物）。对于 RCT，我们计算了药物对重度饮酒和戒酒的药物效应大小（k=139 项研究，19 种药物）。使用药物作为分析单位，我们应用威廉姆森-约克双变量加权最小二乘法估计来解释自变量和因变量的误差。我们还进行了逐一排除的交叉验证模拟，以检验线索渴望药物效应大小对 RCT 重度饮酒和戒酒终点的预测能力。
在人类实验室中，药物对线索诱导的酒精渴望的影响与药物对重度饮酒（r=0.253，SE=0.189，p=0.090）和戒酒（r=0.829，SE=0.747，p=0.133）的影响之间没有显著关系。
目前研究的初步结果对仅使用酒精线索反应作为 AUD 药物治疗开发的早期疗效指标的假设提出了挑战。这些发现表明，应考虑更广泛的早期疗效指标和实验范式，用于新型化合物的 II 期测试。
