Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Psychology, Center on Alcoholism, Substance Abuse, and Addictions, University of New Mexico, Albuquerque NM, USA.
Neuropsychopharmacology. 2018 Mar;43(4):891-899. doi: 10.1038/npp.2017.282. Epub 2017 Nov 20.
Randomized trials of medications for alcohol dependence (AD) often report no differences between active medications. Few studies in AD have tested hypotheses regarding which medication will work best for which patients (ie, precision medicine). The PREDICT study tested acamprosate and naltrexone vs placebo in 426 randomly assigned AD patients in a 3-month treatment. PREDICT proposed individuals whose drinking was driven by positive reinforcement (ie, reward drinkers) would have a better treatment response to naltrexone, whereas individuals whose drinking was driven by negative reinforcement (ie, relief drinkers) would have a better treatment response to acamprosate. The goal of the current analysis was to test this precision medicine hypothesis of the PREDICT study via analyses of subgroups. Results indicated that four phenotypes could be derived using the Inventory of Drinking Situations, a 30-item self-report questionnaire. These were high reward/high relief, high reward/low relief, low reward/high relief, and low reward/low relief phenotypes. Construct validation analyses provided strong support for the validity of these phenotypes. The subgroup of individuals who were predominantly reward drinkers and received naltrexone vs placebo had an 83% reduction in the likelihood of any heavy drinking (large effect size). Cutoff analyses were done for clinical applicability: individuals are reward drinkers and respond to naltrexone if their reward score was higher than their relief score AND their reward score was between 12 and 31. Using naltrexone with individuals who are predominantly reward drinkers produces significantly higher effect sizes than prescribing the medication to a more heterogeneous sample.
随机对照试验药物治疗酒精依赖（AD）往往报告之间没有积极的药物差异。在 AD 中很少有研究测试假设关于哪种药物将最适合哪些患者（即精准医学）。PREDICT 研究在 3 个月的治疗中对 426 名随机分配的 AD 患者进行了安非他酮和纳曲酮与安慰剂的比较。PREDICT 提出，那些饮酒是由正强化（即奖励饮酒者）驱动的个体对纳曲酮的治疗反应会更好，而那些饮酒是由负强化（即缓解饮酒者）驱动的个体对安非他酮的治疗反应会更好。目前分析的目的是通过对亚组的分析来检验 PREDICT 研究的这种精准医学假设。结果表明，使用 30 项自我报告问卷《饮酒情境量表》可以得出四种表型。这些是高奖励/高缓解、高奖励/低缓解、低奖励/高缓解和低奖励/低缓解表型。结构验证分析为这些表型的有效性提供了强有力的支持。主要是奖励饮酒者并接受纳曲酮与安慰剂治疗的亚组人群中，任何重度饮酒的可能性降低了 83%（大效应量）。为了临床适用性进行了临界值分析：如果个体是奖励饮酒者，并且他们的奖励得分高于缓解得分，并且他们的奖励得分在 12 到 31 之间，那么就使用纳曲酮。在主要是奖励饮酒者的个体中使用纳曲酮会产生比给更异质的样本开处方更高的效果。
