Objective:

There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms—rs2832407 (in GRIK1) and rs1799971 (in OPRM1)—on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications.

Methods:

In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events.

Results:

For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response.

Conclusions:

Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

中文翻译：

---

托吡酯与纳曲酮治疗酒精使用障碍：基因型分层双盲随机对照试验

 客观的：

目前还没有托吡酯与纳曲酮等其他治疗酒精使用障碍 (AUD) 的药物疗法进行良好对照和有力的比较试验。此外，关于两种多态性（rs2832407（在GRIK1中）和 rs1799971（在OPRM1中））分别对托吡酯和纳曲酮反应的影响的文献也很复杂。作者试图检验托吡酯和纳曲酮在改善 AUD 结局方面的相对有效性，并检验 rs2832407 和 rs1799971 多态性分别对这些药物反应的作用。

 方法：

在一项为期 12 周、双盲、安慰剂对照、随机、多中心、基因型分层（rs2832407 和 rs1799971）临床试验中，比较托吡酯和纳曲酮治疗 AUD，147 名 AUD 患者被随机分配接受托吡酯或纳曲酮治疗，按基因型分层（rs2832407*CC 和 *AC/AA 基因型以及 rs1799971*AA 和 *AG/GG 基因型）。预定的主要结果是每周酗酒的天数。预定的次要结果包括每周每个饮酒日的标准饮酒量、体重指数（BMI）、渴望、肝损伤标志物、情绪和不良事件。

 结果：

对于每周大量饮酒的天数，治疗时间之间存在近乎显着的相互作用。对于每周每个饮酒日的标准饮酒量，治疗时间之间存在显着的相互作用，这有利于托吡酯。治疗时间有显着的效果，托吡酯比纳曲酮对 BMI、渴望和 γ-谷氨酰转移酶水平有更大的降低。托吡酯组和纳曲酮组分别有 8% 和 5% 的人因副作用而停药。两种多态性均未显示出对治疗反应的影响。

 结论：

在减少大量饮酒方面，托吡酯至少与一线药物纳曲酮一样有效和安全，并且在减少某些临床结果方面更胜一筹。 rs2832407 和 rs1799971 分别对托吡酯和纳曲酮治疗没有影响。