巴氯芬治疗酒精依赖的疗效和安全性：一项随机、双盲、安慰剂对照试验。
Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial.
机构信息
Department of Psychiatry, University of North Carolina at Chapel Hill, CB#7160, Chapel Hill, NC 27599-7160, USA.
出版信息
Alcohol Clin Exp Res. 2010 Nov;34(11):1849-57. doi: 10.1111/j.1530-0277.2010.01273.x.
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(1,73)= 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.
背景
最近的临床试验和病例报告表明，GABA(B) 受体激动剂巴氯芬可能对酒精依赖有效。在意大利进行的两项安慰剂对照试验中，巴氯芬已被证明可提高酒精依赖个体的戒酒率、减少饮酒量、减少渴望感并降低焦虑感。然而，巴氯芬的临床试验数据有限。本研究的目的是在美国测试巴氯芬治疗酒精依赖的疗效和耐受性。
方法
该研究为双盲、安慰剂对照、随机研究，比较了为期 12 周的治疗中 30mg/d 巴氯芬和安慰剂，同时使用了低强度心理社会干预措施 BRENDA 的 8 个疗程。对 121 名受试者进行了筛选，得出 80 名随机受试者（44 名男性），按性别平衡随机分组。主要疗效指标为重度饮酒天数百分比，次要疗效指标为其他饮酒结局、焦虑水平和渴望感。检查了耐受性。
结果
76%的受试者完成了研究。药物组之间在重度饮酒天数百分比上没有差异，平均治疗期间安慰剂组为 25.5%（±23.6%），巴氯芬组为 25.9%（±23.2%）（t(73)=0.59，p=0.56）。同样，药物组之间在无饮酒天数、首次饮酒时间或复饮至重度饮酒时间上也没有差异。巴氯芬与状态焦虑显著降低相关（F(1,73)=5.39，p=0.02）。巴氯芬耐受性良好，仅有 2 名受试者因不良事件停止使用巴氯芬。无严重不良事件。
结论
GABA(B) 受体激动剂巴氯芬可能成为治疗酒精依赖的一种新的药理学方法。尽管有令人鼓舞的临床前数据和之前在意大利进行的巴氯芬阳性临床试验，但本研究并未发现巴氯芬在治疗酒精依赖方面优于安慰剂的证据。需要进一步的临床试验来确定巴氯芬是否对酒精依赖具有治疗效果，如果有，哪些因素可以预测反应。
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