A Double-Blind, Placebo-Controlled Trial Assessing the Efficacy of Levetiracetam Extended-Release in Very Heavy Drinking Alcohol-Dependent Patients
A Double-Blind, Placebo-Controlled Trial Assessing the Efficacy of Levetiracetam Extended-Release in Very Heavy Drinking Alcohol-Dependent Patients
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DOI：
10.1111/j.1530-0277.2011.01716.x
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发表时间：
2012-08-01
影响因子：
3.2
通讯作者：
Stout, Robert
中科院分区：
文献类型：
--
作者：
Fertig, Joanne B.;Ryan, Megan L.;Stout, Robert
背景尽管治疗酒精依赖的药物开发取得了进展，但很少有药物被美国食品和药物管理局批准。某些抗惊厥药物的使用已证明在治疗酒精依赖方面具有潜在疗效。先前的研究表明，抗惊厥药物左乙拉西坦可能对重度饮酒者的酒精依赖人群有益。方法在这项双盲、随机、安慰剂对照的临床试验中，在5个临床中心招募了130名报告重度饮酒的酒精依赖患者。患者接受左乙拉西坦缓释剂（XR）或安慰剂和简短的行为依从性增强治疗干预。在前4周内将左乙拉西坦XR滴定至2，000 mg/d。在第5 - 14周期间维持该目标剂量，并在第15和16周期间逐渐减少。结果左乙拉西坦XR组和安慰剂组在主要结果（重度饮酒天数百分比和无重度饮酒天数的受试者百分比）或其他次要饮酒结果方面均无显著差异。治疗组在一些非饮酒结果上没有差异，包括抑郁、焦虑、情绪和生活质量。观察到的唯一差异是与酒精相关的后果。在维持期内，左乙拉西坦XR治疗组的不良后果显著少于安慰剂组（p = 0.02）。左乙拉西坦XR耐受性良好，与安慰剂相比，疲劳是唯一显著升高的不良事件（分别为53%和24%; p = 0.001）。结论：多中心临床试验显示，左乙拉西坦缓释剂与安慰剂相比，在减少重度饮酒酒精依赖患者的饮酒量方面没有疗效。
Background Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers. Methods In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16. Results No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001). Conclusions This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.