Gabapentin Treatment for Alcohol Dependence A Randomized Clinical Trial
Gabapentin Treatment for Alcohol Dependence A Randomized Clinical Trial
复制标题
DOI：
10.1001/jamainternmed.2013.11950
复制
发表时间：
2014-01-01
影响因子：
39
通讯作者：
Begovic, Adnan
中科院分区：
文献类型：
--
作者：
Mason, Barbara J.;Quello, Susan;Begovic, Adnan
重要性：美国酗酒者中只有不到9%的人使用已批准的戒酒药物。
目的：确定加巴喷丁（一种广泛使用的通用钙通道/γ - 氨基丁酸调节药物）是否以剂量依赖的方式提高持续戒酒和无重度饮酒的比率，并减少与酒精相关的失眠、烦躁和渴望。
设计、参与者和研究地点：2004年至2010年在一家综合医院附属的单一地点门诊临床研究机构进行的一项为期12周、双盲、安慰剂对照、随机剂量范围试验，参与者为150名18岁以上目前患有酒精依赖的男性和女性。
干预措施：口服加巴喷丁（剂量为0[安慰剂]、900毫克或1800毫克/天）以及伴随的手册指导咨询。
主要结果和测量指标：在12周的研究期间，完全戒酒和无重度饮酒的比率（共同主要指标）以及情绪、睡眠和渴望的变化（次要指标）。
结果：加巴喷丁显著提高了戒酒和无重度饮酒的比率。安慰剂组的戒酒率为4.1%（95%置信区间，1.1% - 13.7%），900毫克组为11.1%（95%置信区间，5.2% - 22.2%），1800毫克组为17.0%（95%置信区间，8.9% - 30.1%）（线性剂量效应P = 0.04；1800毫克剂量的需治疗人数[NNT] = 8）。安慰剂组无重度饮酒率为22.5%（95%置信区间，13.6% - 37.2%），900毫克组为29.6%（95%置信区间，19.1% - 42.8%），1800毫克组为44.7%（95%置信区间，31.4% - 58.8%）（线性剂量效应P = 0.02；1800毫克剂量的NNT = 5）。在情绪（F - 2 = 7.37；P = 0.001）、睡眠（F - 2 = 136；P < 0.001）和渴望（F - 2 = 3.56；P = 0.03）的测量指标上也获得了类似的线性剂量效应。没有严重的药物相关不良事件，因不良事件导致的终止研究（150名参与者中有9人）、研究时间（平均[标准差]，9.1[3.8]周）以及研究完成率（150名参与者中有85人）在各组之间没有差异。
结论和相关性：加巴喷丁（特别是1800毫克剂量）在治疗酒精依赖以及与复发相关的失眠、烦躁和渴望症状方面有效，且具有良好的安全性。在初级医疗中增加对酒精依赖的药物治疗实施可能是加巴喷丁作为酒精依赖治疗选择的一个主要益处。
IMPORTANCE Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics.OBJECTIVE To determine if gabapentin, a widely prescribed generic calcium channel/gamma-aminobutyric acid-modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner.DESIGN, PARTICIPANTS AND SETTING A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single-site, outpatient clinical research facility adjoining a general medical hospital.INTERVENTIONS Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling.MAIN OUTCOMES AND MEASURES Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study.RESULTS Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1%(95% CI, 1.1%-13.7%) in the placebo group, 11.1% (95% CI, 5.2%-22.2%) in the 900-mg group, and 17.0%(95% CI, 8.9%-30.1%) in the 1800-mg group (P = .04 for linear dose effect; number needed to treat [NNT] = 8 for 1800 mg). The no heavy drinking rate was 22.5%(95% CI, 13.6%-37.2%) in the placebo group, 29.6%(95% CI, 19.1%-42.8%) in the 900-mg group, and 44.7%(95% CI, 31.4%-58.8%) in the 1800-mg group (P = .02 for linear dose effect; NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F-2 = 7.37; P = .001), sleep (F-2 = 136; P < .001), and craving (F-2 = 3.56; P = .03). There were no serious drug-related adverse events, and terminations owing to adverse events (9 of 150 participants), time in the study (mean [SD], 9.1 [3.8] weeks), and rate of study completion (85 of 150 participants) did not differ among groups.CONCLUSIONS AND RELEVANCE Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence.