Gabapentin Treatment of Benzodiazepine Dependence

描述（由申请人提供）：苯二氮卓类药物依赖是一个日益严重的公共卫生问题，很少有循证治疗方法可用。2010年，美国约有683，000人符合去年镇静催眠药使用障碍的标准，患病率高于海洛因或甲基苯丙胺依赖。1%的美国居民报告非医疗使用镇静催眠药物，这一比例从2008年到2010年增加了20%。 最常用的镇静催眠药是苯二氮卓类。长期使用可诱导GABA神经递质系统的药效学耐受性，具有生理依赖性的个体发现苯二氮卓类药物难以停药，因为戒断或反弹症状，包括自主觉醒、抑郁、焦虑和失眠。现有的循证治疗方法主要针对不符合物质使用障碍标准的苯二氮卓类药物治疗使用者，普遍共识是在数月内逐渐减少苯二氮卓类药物是最佳方法。然而，苯二氮卓类药物依赖患者通常被转诊接受住院戒毒治疗，这会迅速减少患者对苯二氮卓类药物的依赖。长期戒断症状在出院后经常持续存在，使患者易于复发。门诊苯二氮卓类药物依赖的治疗需要更有效的药物治疗策略。 加巴喷丁已被证明是一种安全和耐受性良好的药物，具有低滥用倾向，从而使其成为门诊环境的理想选择。加巴喷丁，如果被证明是有效的促进禁欲，同时减少戒断症状和渴望可以扩大苯二氮卓类依赖门诊患者的治疗选择范围，以及提高治疗效果。 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，比较加巴喷丁与安慰剂在门诊治疗苯二氮卓类药物依赖中的疗效。本项目的目的是研究加巴喷丁对受试者苯二氮卓类药物使用的影响，在一个促进的逐渐减量至戒断模型中，受试者将在研究入组时积极使用苯二氮卓类药物，将引入加巴喷丁治疗，并建议受试者在研究期间逐渐停用苯二氮卓类药物，同时维持加巴喷丁治疗。将使用医学管理的修改版本促进研究药物和其他研究程序的依从性，并包括每周逐渐减少苯二氮卓类药物使用25%的临床说明。 在拟定的研究中未处方苯二氮卓类药物，参与者继续从自己的处方或非处方来源获得苯二氮卓类药物，在初步研究中发现这种方法可行。 参与者将获得代金券奖励， 遵守研究访视出席和完成研究程序，目的是获得高度合规的样本。这项II期临床试验的目的是在进行更大规模的试验之前获得疗效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.