From the, Campbell Family Mental Health Research Institute, (CSH, JDW, JLK), Centre for Addiction and Mental Health, Toronto, ON, Canada.
Institute for Mental Health Policy Research, (CSH, JDW), Centre for Addiction and Mental Health, Toronto, ON, Canada.
Alcohol Clin Exp Res. 2020 Apr;44(4):983-991. doi: 10.1111/acer.14300. Epub 2020 Feb 26.
Initial evidence that OPRM1 genotype moderates the clinical response to naltrexone has not been replicated in prospective clinical trials. However, the use of traditional statistical analyses and clinical endpoints might limit sensitivity for studying pharmacogenetic associations, whereas the use of intensive daily assessments and person-centered analytic methods might increase sensitivity. This study leveraged person-centered analyses and daily measures of alcohol use, craving, and medication adherence to investigate OPRM1 as a moderator of changes in clinical outcomes during naltrexone treatment.
Treatment-seeking participants with alcohol use disorder (n = 58; M = 38 years; 71% male) provided daily cell phone reports of craving and consumption while taking naltrexone as part of a mobile health trial. Daily medication adherence was measured remotely using electronic pill cap recordings. Multilevel modeling and multilevel structural equation modeling analyses evaluated the hypotheses that OPRM1 genotype would moderate prospective reductions in daily alcohol use and craving, and would also moderate within-person associations of daily adherence with same-day craving and consumption.
OPRM1 genotype moderated the association of daily adherence with reduced same-day consumption (p = 0.007) and craving (p = 0.06), with these associations being stronger for participants with the 118G variant. OPRM1 genotype did not moderate changes in craving and consumption over time.
These findings suggest that high-density assessments and person-centered analytic approaches, including modeling within-person variation in medication adherence, could be advantageous for pharmacogenetic studies.
初步证据表明，OPRM1 基因型可调节纳曲酮的临床反应，但在前瞻性临床试验中尚未得到复制。然而，传统的统计分析和临床终点的使用可能会限制研究药物遗传学关联的敏感性，而密集的日常评估和以人为中心的分析方法的使用可能会提高敏感性。本研究利用以人为中心的分析和日常评估酒精使用、渴望和药物依从性，研究 OPRM1 作为纳曲酮治疗期间临床结果变化的调节因素。
寻求治疗的酒精使用障碍参与者（n=58；M=38 岁；71%为男性）在接受纳曲酮治疗期间，通过手机每日报告渴望和消费情况，作为移动健康试验的一部分。使用电子药盒记录远程测量每日药物依从性。多水平建模和多水平结构方程模型分析评估了以下假设：OPRM1 基因型将调节每日酒精使用和渴望的预期减少，并且还将调节每日依从性与当天渴望和消费的个体内关联。
OPRM1 基因型调节了每日依从性与减少当天消费（p=0.007）和渴望（p=0.06）的关联，对于携带 118G 变体的参与者，这些关联更强。OPRM1 基因型并没有调节渴望和消费随时间的变化。
这些发现表明，高密度评估和以人为中心的分析方法，包括建模药物依从性的个体内变异，可能对药物遗传学研究有利。
