A randomized, multicenter, double-blind, placebo-controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence
A randomized, multicenter, double-blind, placebo-controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence
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DOI：
10.1097/jcp.0b013e3181602fd4
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发表时间：
2008-02-01
影响因子：
2.9
通讯作者：
Han, Jian
中科院分区：
文献类型：
--
作者：
Anton, Raymond F.;Kranzler, Henry;Han, Jian
本研究的目的是比较阿立哌唑与安慰剂治疗酗酒者的疗效和安全性。在这项为期12周的多中心、双盲研究中，295名患有精神疾病诊断和统计手册第四版酒精依赖的患者在筛选后随机接受阿立哌唑（以2 mg/d开始，在第28天滴定至最大剂量30 mg/d）或安慰剂治疗，其中患者保持戒酒3天或以上。主要疗效指标为12周内戒断天数的百分比。阿立哌唑组的停药（40.3% vs 26.7%）和治疗相关不良事件（82.8% vs 63.6%）均高于安慰剂组。阿立哌唑组和安慰剂组的平均戒烟天数百分比相似（58.7% vs 63.3%; P = 0.227）。两组间无重度饮酒日的受试者百分比和至首次饮酒日的时间也相当，尽管阿立哌唑组每个饮酒日的饮酒量较少（4.4 vs 5.5; P < 0.001）。阿立哌唑组在第4周（-14.91%vs-2.23%; P = 0.020）和第8周（-16.92%vs-5.33%; P = 0.021）显示碳水化合物缺乏型转铁蛋白百分比的较大降低，这是重度饮酒的生物标志物，但在第12周（-9.06%vs-4.12%; P = 0.298）未显示。在研究终点，阿立哌唑治疗受试者报告的积极主观治疗效果和酒精依赖的总体严重程度低于安慰剂治疗受试者。虽然阿立哌唑和安慰剂在主要终点上没有差异，可能是因为剂量相关的损耗，但对次要结局的影响表明，在较低剂量下可能需要进一步研究阿立哌唑治疗酒精依赖。
The purpose of this study was to compare the efficacy and safety of aripiprazole with placebo in the treatment of alcoholics. In this 12-week multicenter, double-blind study, 295 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence were randomized to treatment with aripiprazole (initiated at 2 mg/d, titrated to a maximum dose of 30 mg/d at day 28) or placebo after screening, wherein patients maintained alcohol abstinence for 3 days or more. The primary efficacy measure was the percentage of days abstinent over 12 weeks. Discontinuations (40.3% vs 26.7%) and treatment-related adverse events (82.8% vs 63.6%) were higher with aripiprazole than with placebo. Mean percentage of days abstinent was similar between aripiprazole and placebo (58.7% vs 63.3%; P = 0.227). Percentage of subjects without a heavy drinking day and the time to first drinking day were also comparable between groups, although the aripiprazole group had fewer drinks per drinking day (4.4 vs 5.5 drinks; P < 0.001). The aripiprazole group showed a larger decrease in percent carbohydrate-deficient transferrin, a biomarker of heavy alcohol consumption at weeks 4 (-14.91% vs -2.23%; P = 0.020) and 8 (-16.92% vs -5.33%; P = 0.021), although not at week 12 (-9.06% vs -4.12%; P = 0.298). At study end point, aripiprazole-treated subjects reported more positive subjective treatment effects and less overall severity of alcohol dependence than placebo-treated subjects. Although there was no difference between aripiprazole and placebo on the primary end point, possibly because of dose-related attrition, effects on the secondary outcomes suggest that further study of aripiprazole for treatment of alcohol dependence may be warranted at lower doses.