Brown University Alpert Medical School, Center for Alcohol and Addiction Studies, 121 South Main Street, Room 404, Providence, Rhode Island 02903, USA.
J Stud Alcohol Drugs. 2011 Nov;72(6):1012-8. doi: 10.15288/jsad.2011.72.1012.
The efficacy of naltrexone (Revia, Vivitrol) for the treatment of alcohol dependence exhibits a high degree of heterogeneity. The aim of the current study was to evaluate the extent to which variability in patient adherence to treatment contributed to the range of clinical responses observed during naltrexone treatment.
A systematic review was conducted of efficacy trials of naltrexone for the treatment of alcohol dependence to evaluate the level of adherence monitoring.
Of 49 identified trials, 22 (49%) met the inclusion criteria of being randomized, double-blind, placebo-controlled trials that reported adherence. The "adherence-assurance score" of these trials was calculated as a function of the frequency with which "low," "moderate," or "high" confidence levels of adherence monitoring were used. Of these 22 randomized, controlled trials, only 3 (14%) met criteria for high levels of adherence assurance, 5 (23%) met medium adherenceassurance criteria, and 14 (64%) met low adherence criteria. Of the three high-assurance studies, one used direct supervision of thrice-weekly oral dosing of naltrexone, and two used extended-release injectable formulations of naltrexone administered once per month. The Spearman correlation between risk ratios for return to heavy drinking (for naltrexone vs. placebo) and the level of adherence assurance (low vs. medium vs. high) was significant (r = -.62, p = .025).
These findings suggest that the modest effect sizes for naltrexone reported in systematic reviews and meta-analyses may be attributable, at least in part, to variability in naltrexone adherence rates. High-assurance adherence strategies should be standard practice in clinical trials of medications being evaluated for the treatment of alcohol dependence.
纳曲酮（Revia，Vivitrol）治疗酒精依赖的疗效存在高度异质性。本研究旨在评估患者对治疗的依从性变化在多大程度上导致了纳曲酮治疗期间观察到的临床反应范围的变化。
对纳曲酮治疗酒精依赖的疗效试验进行系统评价，以评估依从性监测的程度。
在确定的 49 项试验中，有 22 项（49%）符合随机、双盲、安慰剂对照试验的纳入标准，并报告了依从性。这些试验的“依从性保证评分”是根据使用“低、中或高”依从性监测置信度的频率计算的。在这 22 项随机对照试验中，只有 3 项（14%）符合高度依从性保证标准，5 项（23%）符合中度依从性保证标准，14 项（64%）符合低度依从性标准。在这三项高保证研究中，有一项研究采用了每周三次口服纳曲酮的直接监督，两项研究采用了每月一次的纳曲酮延长释放注射制剂。纳曲酮与安慰剂相比，回归重度饮酒的风险比（RR）与依从性保证水平（低、中、高）之间的斯皮尔曼相关系数显著（r=-.62，p=0.025）。
这些发现表明，系统评价和荟萃分析报告的纳曲酮的适度疗效可能部分归因于纳曲酮依从率的变化。在评估用于治疗酒精依赖的药物的临床试验中，高保证依从性策略应成为标准做法。
