HSR&D Center for Health Care Evaluation, VA Palo Alto Health Care System, Stanford University Medical School, Menlo Park, CA 94025, USA.
Alcohol Clin Exp Res. 2013 Jun;37(6):1064-8. doi: 10.1111/acer.12067. Epub 2013 Feb 7.
Oral naltrexone is an FDA-approved medication for treating alcohol use disorders. Although its efficacy has been supported in multiple clinical trials, an earlier review found that its effect sizes (ESs) on relapse to heavy drinking and, to a lesser extent, percent days drinking were smaller in more recent trials and in multicenter than in single-site studies. We examined whether these findings held when studies from 2004 to 2009 were taken into account, and whether single-site versus multicenter trials, the use of placebo run-in periods, and placebo group improvement accounted for variation in naltrexone effects and decreasing effects over time.
A multivariate meta-analysis of naltrexone pharmacotherapy trials for alcohol use disorders was conducted. All analyses simultaneously modeled ESs on outcomes of percent days abstinent and relapse to heavy drinking. Potential moderators of medication effects that were examined included publication year, multicenter design (vs. single site), placebo run-in period, and placebo group improvement.
Statistically significant between-group differences on percent days abstinent (the inverse of percent days drinking) and relapse to heavy drinking favored naltrexone over placebo. Year of publication was a significant moderator for both outcomes, with more recent trials having smaller ESs. Neither multi- versus single-site study, the interaction between multi- versus single-site study and year of publication, nor placebo run-in period was a significant moderator of naltrexone effects. Although placebo group improvement was modestly associated with smaller between-group naltrexone versus placebo ESs, only 21 studies provided usable information on placebo group improvement. Within those studies, there was no relationship between naltrexone ESs and time, so placebo group improvement was not examined as a moderator of that relationship.
Naltrexone ESs have attenuated over time. Moderators that explain why effects have been decreasing remain to be determined.
口服纳曲酮是一种经美国食品药品监督管理局批准用于治疗酒精使用障碍的药物。尽管多项临床试验均支持其疗效，但早期的一项综述发现，在最近的试验中和多中心研究中，与单中心研究相比，纳曲酮对重度饮酒复发的效果量（ES）以及在较小程度上对饮酒天数的影响较小。我们研究了在考虑到 2004 年至 2009 年的研究后，这些发现是否仍然成立，以及单中心与多中心试验、安慰剂导入期的使用以及安慰剂组的改善是否解释了纳曲酮作用的变化以及随时间推移而降低的作用。
对酒精使用障碍的纳曲酮药物治疗试验进行了多变量荟萃分析。所有分析均同时对无饮酒天数的 ES 和重度饮酒复发的结果进行建模。所检查的药物作用的潜在调节因素包括出版年份、多中心设计（与单中心相比）、安慰剂导入期和安慰剂组的改善。
无饮酒天数（即饮酒天数的倒数）和重度饮酒复发的组间差异具有统计学意义，纳曲酮优于安慰剂。出版年份是这两个结果的显著调节因素，最近的试验 ES 较小。多中心与单中心研究之间、多中心与单中心研究与出版年份之间的相互作用以及安慰剂导入期均不是纳曲酮作用的显著调节因素。尽管安慰剂组的改善与纳曲酮与安慰剂相比较小的组间 ES 适度相关，但只有 21 项研究提供了关于安慰剂组改善的可用信息。在这些研究中，纳曲酮 ES 与时间之间没有关系，因此未研究安慰剂组改善是否为这种关系的调节因素。
纳曲酮的 ES 随时间减弱。仍需确定解释作用减弱的调节因素。
