Efficacy and Safety of Baclofen for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial
Efficacy and Safety of Baclofen for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial
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DOI：
10.1111/j.1530-0277.2010.01273.x
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发表时间：
2010-11-01
影响因子：
3.2
通讯作者：
Flannery, Barbara A.
中科院分区：
文献类型：
--
作者：
Garbutt, James C.;Kampov-Polevoy, Alexei B.;Flannery, Barbara A.
背景：最近的临床试验和病例报告表明，巴氯芬，一种GABA(B)激动剂，可能对酒精依赖有疗效。在意大利进行的两项安慰剂对照试验中，巴氯芬已被证明可以增强酒精依赖者的戒断、减少饮酒量、减少渴望和减少焦虑。然而，巴氯芬的临床试验数据有限。本研究的目的是测试巴氯芬对美国酒精依赖的疗效和耐受性。方法：该研究是一项双盲、安慰剂对照、随机研究，比较30毫克/天的巴氯芬和安慰剂，治疗12周，并使用8次低强度心理社会干预BRENDA。121名受试者经过筛选，产生80名随机受试者（男性44名），性别随机化平衡。重度饮酒天数百分比是主要指标，其他饮酒指标、焦虑水平和渴望程度是次要指标。检验了耐受性。结果：76%的受试者完成了研究。在治疗期间，重度饮酒天数的百分比在药物条件下没有差异，安慰剂组的平均比率为25.5%(+/- 23.6%)，巴氯芬组的平均比率为25.9% (+/- 23.2%)（t(73) = 0.59, p = 0.56）。同样，药物状况在戒酒天数百分比、首次饮酒时间或重度饮酒复发时间方面也没有差异。巴氯芬与状态焦虑的显著降低相关（F-1,F-73 = 5.39, p = 0.02）。巴氯芬耐受性良好，仅有2人因不良事件停药。无严重不良事件发生。结论：巴氯芬是一种GABA(B)激动剂，可能是治疗酒精依赖的一种新的药物治疗方法。尽管巴氯芬在意大利的临床前数据和阳性临床试验令人鼓舞，但目前的试验并没有发现巴氯芬在治疗酒精依赖方面优于安慰剂的证据。需要更多的临床试验工作来确定巴氯芬对酒精依赖是否有治疗效果，如果有，哪些因素可以预测反应。
Background:Recent clinical trials and case-reports indicate that baclofen, a GABA(B) agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol-dependent individuals in 2 placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States.Methods:The study was a double-blind, placebo-controlled, randomized study comparing 30 mg/d of baclofen to placebo over 12 weeks of treatment and utilizing 8 sessions of BRENDA, a low-intensity psychosocial intervention. One hundred and twenty-one subjects were screened to yield 80 randomized subjects (44 men) with randomization balanced for gender. Percent heavy drinking days was the primary outcome measure with other drinking outcomes, anxiety levels, and craving as secondary outcomes. Tolerability was examined.Results:Seventy-six percent of subjects completed the study. No difference by drug condition was seen in percentage of heavy drinking days where on-average rates were 25.5% (+/- 23.6%) for placebo and 25.9% (+/- 23.2%) for baclofen during treatment (t(73) = 0.59, p = 0.56). Similarly, no differences were seen by drug condition in percentage of days abstinent, time to first drink, or time to relapse to heavy drinking. Baclofen was associated with a significant reduction in state anxiety (F-1,F-73 = 5.39, p = 0.02). Baclofen was well tolerated with only 2 individuals stopping baclofen because of adverse events. There were no serious adverse events.Conclusions:Baclofen, a GABA(B) agonist, represents a possible new pharmacotherapeutic approach to alcohol dependence. Despite encouraging preclinical data and prior positive clinical trials with baclofen in Italy, the current trial did not find evidence that baclofen is superior to placebo in the treatment of alcohol dependence. Additional clinical trial work is necessary to establish whether baclofen does or does not have therapeutic efficacy in alcohol dependence and, if it does, what factors are predictive of response.