Gabapentin Treatment of Benzodiazepine Dependence

描述(申请人提供)：苯二氮卓类药物依赖是一个日益严重的公共卫生问题，几乎没有循证的治疗方法可用。2010年，美国约有68.3万人符合过去一年镇静-催眠药物使用障碍的标准，患病率高于海洛因或甲基苯丙胺依赖。1%的美国居民报告说，他们使用非医疗手段的镇静催眠药，这一比例从2008年到2010年增长了20%。最常用的镇静催眠药是苯二氮卓类。长期使用会导致GABA神经递质系统的药效耐受，有生理依赖的人发现苯二氮卓类药物很难停用，因为停药或反弹症状，包括自主神经唤醒、抑郁、焦虑和失眠。现有的循证治疗方法主要针对不符合药物使用障碍标准的苯二氮卓类药物的治疗性使用者，普遍认为在几个月的时间内逐步减少苯二氮卓类药物是最佳方法。然而，苯二氮卓依赖的患者通常会被转介到住院戒毒治疗中，这会迅速减少患者对苯二氮卓类药物的依赖。长期的戒断症状经常在出院后持续存在，使患者容易复发。在门诊环境中治疗苯二氮类药物依赖需要更有效的药物治疗策略。事实证明，加巴喷丁是一种安全、耐受性好的药物，滥用风险很低，因此非常适合在门诊使用。加巴喷丁如果被证明在促进戒断方面有效，同时减少戒断症状和渴求，可以扩大苯二氮依赖门诊患者的治疗选择范围，并提高治疗结果。拟议的探索性开发研究项目是一项双盲随机对照临床试验，比较加巴喷丁和安慰剂在门诊治疗苯二氮类药物依赖方面的疗效。该项目的目标是研究加巴喷丁对受试者苯二氮卓类药物使用的影响，在简化的逐步戒断模型中，受试者将在研究开始时积极使用苯二氮卓类药物，将引入加巴喷丁治疗，并将建议受试者在研究期间逐步停止苯二氮卓类药物的使用，同时维持加巴喷丁治疗。医疗管理的修订版将用于促进遵守研究用药和其他研究程序，并包括逐步减少每周25%苯二氮卓类药物使用的临床指导。苯二氮卓类药物在拟议的研究中没有处方，参与者继续从他们自己的处方或非处方来源获得苯二氮卓类药物，这一方法在试点研究中被发现是可行的。参与者将获得以下奖励的代金券 遵守研究访问出席并完成研究程序，目标是获得高度符合要求的样本。这项II期临床试验的目标是在进行更大规模的试验之前获得有效性和安全性的初步证据。

DESCRIPTION (provided by applicant): Benzodiazepine dependence is a growing public health problem for which very few evidenced-based treatment approaches are available. Approximately 683,000 individuals met past year criteria for sedative- hypnotic use disorders in the US during 2010, a prevalence greater than heroin or methamphetamine dependence. One percent of US residents report nonmedical use of sedative-hypnotic medications, a rate that has increased 20% from 2008 to 2010. The most commonly prescribed sedative-hypnotic agents are the benzodiazepines. Chronic use induces pharmacodynamic tolerance in the GABA neurotransmitter system and individuals with physiological dependence find benzodiazepines difficult to discontinue because of withdrawal or rebound symptoms, which include autonomic arousal, depression, anxiety, and insomnia. Available evidence-based treatment approaches have been primarily directed at therapeutic users of benzodiazepines who do not meet criteria for a substance use disorder, with a general consensus that the gradual taper of benzodiazepines over a period of several months is the optimal approach. However, patients with benzodiazepine dependence are typically referred for inpatient detoxification treatment, which rapidly tapers patients off benzodiazepines. Protracted withdrawal symptoms frequently persist after discharge, predisposing patients to relapse. More effective pharmacotherapeutic strategies are needed for the treatment of benzodiazepine dependence in the outpatient setting. Gabapentin has proven to be a safe and well-tolerated medication with a low abuse liability, thereby making it ideal for use in the outpatient setting. Gabapentin, if proven to be efficacious in promoting abstinence, while reducing withdrawal symptoms and cravings could broaden the range of treatment options for benzodiazepine-dependent outpatients as well as enhance treatment outcomes. The proposed Exploratory Development research project is a double-blind randomized controlled clinical trial comparing the efficacy of gabapentin to placebo for the outpatient treatment of benzodiazepine dependence. The goal of this project is to study the effects of gabapentin on the participants' benzodiazepine use in a facilitated taper-to-abstinence model, where participants will be actively using benzodiazepines at study entry, gabapentin treatment will be introduced, and participants will be counseled to gradually discontinue benzodiazepine use over the study period while gabapentin treatment is maintained. A modified version of Medical Management will be used to facilitate compliance with study medication and other study procedures, and includes clinical instruction for gradually reducing benzodiazepine use 25% per week. Benzodiazepines are not prescribed in the proposed study participants continue to obtain benzodiazepines from their own prescribed or non prescribed sources, an approach found to be feasible in the pilot study. Participants will receive voucher incentives for compliance with study visit attendance and completing study procedures, with the objective of achieving a highly compliant sample. The goal of this phase II clinical trial is to obtain preliminary evidence of efficacy and safety before conducting a larger trial.