Efficacy of a Combination of Flumazenil and Gabapentin in the Treatment of Alcohol Dependence Relationship to Alcohol Withdrawal Symptoms
Efficacy of a Combination of Flumazenil and Gabapentin in the Treatment of Alcohol Dependence Relationship to Alcohol Withdrawal Symptoms
复制标题
DOI：
10.1097/jcp.0b013e3181aba6a4
复制
发表时间：
2009-08-01
影响因子：
2.9
通讯作者：
Malcolm, Robert
中科院分区：
文献类型：
--
作者：
Anton, Raymond F.;Myrick, Hugh;Malcolm, Robert
改善酒精依赖的治疗是当务之急，包括定义可能有不同反应的亚型。我们评估了静脉注射氟马西尼 (FMZ) 和口服加巴喷丁 (GBP) 的药物组合，对治疗前出现和未出现酒精戒断 (AW) 症状的酗酒者进行评估。 60 名酒精依赖者（44 名低 AW 和 16 名高 AW）被随机分配接受 FMZ（连续 2 天 20 分钟增量推注 2 毫克）和 GBP（每晚最多 1200 毫克，持续 39 天）或其非活性安慰剂。在前两天测量酒精戒断情况，并在每周评估和行为咨询课程中监测饮酒、睡眠参数和不良事件。治疗期间的戒酒天数百分比（PDA）和首次大量饮酒的时间（TFHD）是主要结果变量。治疗前 AW 状态与 PDA (P = 0.0006) 和 TFHD (P = 0.06) 药物组之间存在交互作用。如果使用活性药物治疗，高 AW 组的患者有更多的 PDA 和更多的 TFHD，而低 AW 组的患者如果使用安慰剂治疗，则有更多的 PDA 和更多的 TFHD。对于那些完全戒断的人来说，这种相互作用仍然存在（P = 0.03），并通过碳水化合物缺乏转铁蛋白百分比值得到证实。此外，治疗后反应模式持续长达 8 周。此外，在 AW 高的患者中，与安慰剂组相比，活性药物组的 AW 症状有更大的改善。这些结果表明对 FMZ/GBP 治疗的不同反应取决于治疗前的 AW 状态，在未来的治疗试验中应考虑到这一点。
Improved treatment of alcohol dependence is a high priority, including defining subtypes that might respond differently. We evaluated a medication combination of intravenous flumazenil (FMZ) and oral gabapentin (GBP) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal (AW) symptoms. Sixty alcohol-dependent individuals (44 with low AW and 16 with high AW) were randomized to receive FMZ (2 mg of incremental bolus for 20 minutes for 2 consecutive days) and GBP (up to 1200 mg nightly for 39 days) or their inactive placebos. Alcohol withdrawal was measured for the first 2 days, and drinking, sleep parameters, and adverse events were monitored during weekly evaluations, along with behavioral counseling sessions. Percent days abstinent (PDA) during treatment and time to first heavy drinking (TFHD) day were primary outcome variables. There was an interaction between the pretreatment AW status and the medication group on PDA (P = 0.0006) and TFHD (P = 0.06). Those in the high AW group had more PDA and more TFHD if treated with active medications, whereas those in the low AW group had more PDA and more TFHD if treated with placebo. This interaction remained for those totally abstinent (P = 0.03) and was confirmed by percent carbohydrate-deficient transferrin values. In addition, the pattern of response remained up to 8 weeks after treatment. In addition, in those with high AW, greater improvement in AW symptoms was observed in the active medication group compared with the placebo group. These results suggest a differential response to FMZ/GBP treatment, depending on pretreatment AW status that should be taken into account during future treatment trials.