Gabapentin for Abstinence Initiation in Alcohol Dependence

加巴喷丁用于酒精依赖者的戒酒

• 批准号: 7899617
• 负责人: John J Mariani
• 金额: $ 23.99万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7899617
• 关键词: Abstinence; Acute; Adverse effects; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcohols; Anticonvulsants; Anxiety; Back; Behavior Therapy; Benzodiazepines; Carbamazepine; Clinical; Complex; Development; Double-Blind Method; Drug Interactions; Drug Kinetics; Drug Metabolic Detoxication; Evaluation; Exhibits; Gamma-glutamyl transferase; Goals; Heavy Drinking; Incidence; Inpatients; Institutes; Light; Measurement; Measures; Medical; Methods; Modeling; Naltrexone; Outcome Measure; Outpatients; Participant; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Public Health; Randomized; Randomized Controlled Clinical Trials; Relapse; Research Project Grants; Risk; Safety; Serum; Sleeplessness; Symptoms; Therapeutic; Time; TimeLine; Titrations; Treatment outcome; United States; Withdrawal; Withdrawal Symptom; Woman; acamprosate; alcohol abstinence; clinically significant; comparative efficacy; compliance behavior; craving; disorder later incidence prevention; drinking; economic cost; gabapentin; health economics; meetings; men; pilot trial; primary outcome; public health relevance; reduced alcohol use; secondary outcome; topiramate; trial comparing

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.

描述(由申请人提供)：尽管在药理学和行为干预的发展方面取得了实质性进展，但酒精依赖在美国仍然是一个严重的公共卫生问题，治疗设施方面仍然存在重大差距。从概念上讲，酒精依赖的理想药物疗法是：1)对经常饮酒的患者使用是安全的；2)提供防止戒酒的保护；3)促进戒酒；4)减少戒酒患者的渴望和复发风险；5)滥用的可能性很低。目前没有一种治疗酒精依赖的药物疗法符合这些标准，因此代表着一个重要的未得到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)方面的有效性证据有限，作为复发预防药物的有效性证据也有限。事实证明，加巴喷丁是一种耐受性很好的药物，滥用风险很低，因此非常适合在门诊使用。拟议的试点项目是在禁欲启动模型中研究加巴喷丁对参与者酒精使用的影响，在该模型中，参与者在研究开始时积极使用酒精，并在整个研究期间测量自基线以来使用模式的变化。戒酒启动方法的优势是，它更准确地反映了酒精依赖最常见的临床表现：积极饮酒的患者，住院戒毒对他们来说是不必要或不可接受的。该项目的具体目的是确定抗惊厥剂加巴喷丁在治疗酒精依赖患者的酒精戒断症状、减少酒精消耗和促进戒断方面是否比安慰剂更有效。主要结果指标将是1)临床研究所戒酒(CIWA-AR)和2)每周大量饮酒天数(定义为男性至少5次饮酒，女性至少4次饮酒的任何一天)，这是通过时间线追踪法测量的。第二个假设是，加巴喷丁在减少酒精使用方面将优于安慰剂，这是通过次要结果来衡量的，如每天饮酒量、每天饮酒量、戒酒百分比和对伽马-谷氨酰转移酶(GGT)血清水平的连续测量。拟议的项目是一项为期8周的随机、双盲、安慰剂对照的先导试验，以评估加巴喷丁在60名门诊患者中治疗酒精依赖的疗效。所有参与者每周都将接受支持性行为治疗，以促进戒酒和其他物质的戒断，鼓励参加12步会议，并促进研究药物的依从性。拟议的研究项目将是第一个使用禁欲启动模型对加巴喷丁进行研究的项目，如果被证明有效，这将具有极大的临床实用价值。 与公共健康相关：在美国，酒精依赖是一个严重的公共健康问题，造成了巨大的健康和经济成本。现有的酒精依赖药物治疗方法有限，因为还没有发现一种单一的药物可以用于积极饮酒的门诊患者，治疗戒断和减少酒精消费。确定一种可以同时达到这些治疗目标的药物可能会增加酒精依赖药物治疗的可得性和可及性。