Gabapentin for Abstinence Initiation in Alcohol Dependence

描述（由申请人提供）：尽管在药物和行为干预的开发方面取得了实质性进展，但酒精依赖仍然是美国的一个重大公共卫生问题，在治疗设备方面仍然存在重大差距。从概念上讲，酒精依赖的理想药物治疗应：1）对主动饮酒患者安全; 2）提供防止酒精戒断的保护; 3）促进酒精戒断; 4）减少戒断患者的渴望和复发风险; 5）滥用的可能性较低。目前没有酒精依赖的药物治疗符合这些标准，因此代表了一个重要的未满足的公共卫生需求。加巴喷丁是一种抗惊厥药物，在治疗酒精戒断症状和急性戒断后症状（如失眠和焦虑）方面的疗效证据有限，作为复发预防剂的疗效证据也有限。加巴喷丁已被证明是一种耐受性良好的药物，具有低滥用倾向，从而使其成为门诊环境中使用的理想药物。拟议的试点项目是研究加巴喷丁对参与者在戒酒-启动模型中使用酒精的影响，其中参与者在进入研究时积极使用酒精，并在整个研究期间测量使用模式相对于基线的变化。戒酒启动方法的优点是，它可以更准确地反映酒精依赖最常见的临床表现：一个积极饮酒的病人，住院戒毒是不必要的或不可接受的。该项目的具体目的是确定抗惊厥剂加巴喷丁在治疗酒精戒断症状、减少酒精消费和促进酒精依赖患者戒酒方面是否比安慰剂更有效。主要结局指标将是1）临床研究所酒精戒断（CIWA-Ar）和2）每周大量饮酒天数（定义为男性饮酒次数至少为5次，女性至少为4次的任何一天），通过时间轴随访方法测量。次要假设是加巴喷丁在减少酒精使用方面上级安慰剂，如通过次要结果测量的，如每天的饮酒量，每个饮酒日的饮酒量，戒酒天数百分比和γ-谷氨酰转移酶（GGT）血清水平的连续测量。该项目是一项为期8周的随机、双盲、安慰剂对照的先导性试验，旨在评估加巴喷丁治疗60例门诊患者酒依赖的疗效。所有受试者将接受每周一次的支持性行为治疗，促进戒酒和其他物质，鼓励参加12步会议，并促进对研究药物的依从性。拟议的研究项目将是第一个使用禁欲启动模型的加巴喷丁研究，如果证明有效，将具有很大的临床实用性。 公共卫生相关性：酒精依赖在美国是一个重要的公共卫生问题，造成了巨大的健康和经济成本。酒精依赖的可用药物治疗是有限的，因为没有一种单一的药物已被确定，可以给予主动饮酒门诊患者，治疗戒断，并减少酒精消费。确定一种药物，可以同时服务于这些治疗目标，将有可能增加酒精依赖药物治疗的可用性和可及性。

DESCRIPTION (provided by applicant): Despite substantial advances in the development of pharmacological and behavioral interventions, alcohol dependence continues to be a significant public health problem in the U.S., and significant gaps in the treatment armamentarium remain. Conceptually, the ideal pharmacotherapy for alcohol dependence would: 1) be safe when administered to actively drinking patients; 2) provide protection against alcohol withdrawal; 3) promote alcohol abstinence; 4) decrease craving and the risk of relapse in abstinent patients; and 5) have a low potential for abuse. No current pharmacotherapy for alcohol dependence meets these criteria and thus represents an important unmet public health need. Gabapentin is an anticonvulsant medication with limited evidence of efficacy in treating the symptoms of alcohol withdrawal and post-acute withdrawal symptoms, such as insomnia and anxiety, as well as limited evidence of efficacy as a relapse prevention agent. Gabapentin has proven to be a well-tolerated medication with a low abuse liability, thereby making it ideal for use in the outpatient setting. The proposed pilot project is to study the effects of gabapentin on the participants' use of alcohol in an abstinence-initiation model, where participants are actively using alcohol at study entry, and the change in use pattern from baseline is measured throughout the study period. The advantage of the abstinence-initiation approach is that it serves as a more accurate mirror of the most common clinical presentation of alcohol dependence: an actively-drinking patient for whom inpatient detoxification is unnecessary or unacceptable. The specific aim of the project is to determine whether the anticonvulsant agent gabapentin is more effective than placebo in treating alcohol withdrawal symptoms and reducing alcohol consumption and promoting abstinence in alcohol-dependent patients. The primary outcome measures will be 1) the Clinical Institute Withdrawal Alcohol (CIWA-Ar) and 2) the number of the heavy drinking days (defined as any day where the number of drinks was at least 5 for men and at least 4 for women) per week as measured by the timeline follow-back method. The secondary hypothesis is that gabapentin will be superior to placebo in reducing alcohol use as measured by secondary outcomes such as amount of drinks per day, amount of drinks per drinking day, percent days abstinent and serial measurement of gamma-glutamyl transferase (GGT) serum levels. The proposed project is an 8-week randomized double-blind placebo-controlled pilot trial to evaluate the efficacy of gabapentin in the treatment of alcohol dependence in 60 outpatients. All participants will receive weekly supportive behavioral treatment that promotes abstinence from alcohol and other substances, encourages 12-step meeting attendance, and facilitates compliance with study medication. The proposed research project would be the first study of gabapentin using the abstinence-initiation model, which would be of great clinical utility if proven to be effective. PUBLIC HEALTH RELEVANCE: Alcohol dependence is significant public health problem in the U.S. responsible for substantial health and economic costs. The available medication treatments for alcohol dependence are limited in that no one single agent has been identified that can be administered to actively drinking outpatients, treat withdrawal, and reduce alcohol consumption. Identification of a medication that could serve these therapeutic objectives simultaneously would potentially increase the both availability and accessibility of medication treatment for alcohol dependence.