The Declining Efficacy of Naltrexone Pharmacotherapy for Alcohol Use Disorders Over Time: A Multivariate Meta-Analysis
The Declining Efficacy of Naltrexone Pharmacotherapy for Alcohol Use Disorders Over Time: A Multivariate Meta-Analysis
复制标题
DOI：
10.1111/acer.12067
复制
发表时间：
2013-06-01
影响因子：
3.2
通讯作者：
Finney, John
中科院分区：
文献类型：
--
作者：
Del Re, A. C.;Maisel, Natalya;Finney, John
背景口服纳曲酮是FDA批准的治疗酒精使用障碍的药物。尽管它的有效性已经在多个临床试验中得到支持，但早期的一项综述发现，在最近的试验和多中心研究中，它对酗酒复发的影响大小(Ess)以及在较小程度上饮酒的天数百分比比单中心研究要小。我们检查了在考虑2004年至2009年的研究时，这些发现是否成立，以及单地点试验与多中心试验、安慰剂磨合期的使用以及安慰剂组的改善是否解释了纳曲酮效果的变化和随着时间的推移效果降低的原因。方法对纳曲酮治疗酒精使用障碍的临床试验进行多因素Meta分析。所有分析同时以戒酒和酗酒复发的百分比天数作为ESS的模型。研究的药物效应的潜在调节因素包括发表年份、多中心设计(与单一试验相比)、安慰剂试入期和安慰剂组的改善。结果在戒酒天数百分比(与饮酒天数百分比相反)和再次大量饮酒方面，组间差异有统计学意义，纳曲酮优于安慰剂。发表的年份对这两种结果都是一个重要的调节因素，最近的试验有较小的ESS。无论是多站点研究还是单站点研究，多站点研究与单站点研究和发表年份之间的相互作用，以及安慰剂磨合期都不是纳曲酮效应的显著调节因素。尽管安慰剂组的改善与纳曲酮与安慰剂组之间较小的组间改善略有关联，但只有21项研究提供了关于安慰剂组改善的有用信息。在这些研究中，纳曲酮Ess与时间之间没有关系，因此安慰剂组的改善没有被视为这种关系的调节因素。结论随着时间的推移，纳曲酮ESS逐渐减弱。解释为什么影响一直在减少的主持人还有待确定。
Background 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. Methods 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. Results 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. Conclusions Naltrexone ESs have attenuated over time. Moderators that explain why effects have been decreasing remain to be determined.