BEH PHARM TREATMENTS FOR ALCOHOL/NICOTINE DEPENDENCE

申请人摘要：酒精滥用和依赖以及尼古丁依赖 是美国的主要健康问题。 一起 联合药物疗法可能为治疗癌症提供有希望的新方向。 治疗双重依赖的病人。 具体来说，透皮尼古丁 替代（TNR）和纳洛酮（NTX）具有显著的临床效用， 分别治疗吸烟和酗酒。 这些药物， 当同时使用时，可能有助于在饮酒期间戒烟 治疗 这种药物效果将在以下情况下得到优化： 辅助心理治疗干预，特别是那些强调 复发预防（RP）技能培训。 我们的论点是， TNR和NTX的同时应用在这方面有一定的作用 尼古丁-酒精治疗，迫切需要 前瞻性临床试验。 拟定的双盲、安慰剂对照、2x2析因研究将 通过交叉试验确定两种处理之间的潜在相互作用 酒精治疗（NTX 50 mg/d vs.安慰剂）联合吸烟治疗（活性 TNR对比安慰剂）。 两种药物治疗都将在 认知行为RP技能训练疗法，强调 吸烟和饮酒之间的联系。 酒精-尼古丁依赖受试者 （n=200）将被随机分配到四个门诊治疗之一 条件，然后开始为期12周的试验，包括每周的诊所访问。 吸烟状况将基于自我报告、呼出空气一氧化碳和 唾液可替宁水平 酒精消费将通过以下方式衡量： 自我报告、呼气酒精读数、间接报告和肝功能 试验. 饮酒和吸烟的主要疗效参数包括 至失效/复发的时间和累积缺勤持续时间。 次要疗效 措施将包括酒精和吸烟消费，临床全球 印象、治疗中的保持、ASI评分和药物依从性。 我们预测，接受TNR和NTX作为RP替代品的受试者将有 两种物质的戒断率高于不戒断的受试者 接受这些药物治疗。 本研究的次要目的将 包括：1）评估过程变量的影响（应对， 自我效能，渴望，抑郁）对治疗结果的影响; 2）测试 患者变量的预后意义（尼古丁/酒精依赖， 准备改变，压力，抑郁），以及探索潜力 患者-治疗匹配效果; 3）评价治疗的维持情况 在6个月的随访期内获得收益。 结果将推动我们的 了解与并发症相关的临床研究问题 治疗酒精和尼古丁双重依赖患者。 最后， 建议的研究将继续进行，并扩大我们正在进行的 研究计划旨在评估行为和 药物依赖的药物干预。

APPLICANT'S ABSTRACT: Alcohol abuse and dependence and nicotine dependence are major health problems in the U.S. Each is exacerbated when used together. Combined pharmacotherapies may offer promising new directions for treating dually-dependent patients. Specifically, transdermal nicotine replacement (TNR) and naltrexone (NTX) have significant clinical utility for the treatment of smoking and alcoholism, respectively. These medications, when used simultaneously, may facilitate smoking cessation during alcohol treatment. Such medication effects would be optimized in the context of adjuvant psychotherapeutic interventions, particularly those emphasizing relapse prevention (RP) skills training. It is our contention, that the concurrent application of TNR and NTX has a definite role within the context of nicotine-alcohol treatment and that there is a pressing need for a prospective clinical trial. The proposed double-blind, placebo controlled, 2x2 factorial study will determine the potential interactions between the two treatments by crossing alcohol treatment (NTX 50mg/d vs. placebo) with smoking treatment (active TNR vs. placebo). Both pharmacotherapies will be applied within a context of a cognitive-behavioral RP skills training therapy that emphasizes the linkage between smoking and drinking. Alcohol-nicotine dependent subjects (n=200) will be randomly assigned to one of four outpatient treatment conditions, then begin the 12-week trial involving weekly clinic visits. Smoking status will be based on self-report, expired air carbon monoxide and saliva cotinine levels. Alcohol consumption will be measured by self-report, breath alcohol readings, collateral reports, and liver function tests. Primary efficacy parameters for drinking and smoking will include time to lapse/relapse and cumulative absence duration. Secondary efficacy measures will include alcohol and smoking consumption, clinical global impression, retention in treatment, ASI scores, and medication compliance. We predict that subjects receiving TNR and NTX as adjuncts to RP will have higher rates of abstinence from both substances than subjects who do not receive these pharmacologic adjuncts. Secondary aims of this study will include: 1) assess the influences of process variables (coping, self-efficacy, craving, depression) on treatment outcome; 2) test the prognostic significance of patient variables (nicotine/alcohol dependence, readiness to change, stress, depression), as well as explore potential patient-treatment matching effects; 3) evaluate the maintenance of treatment gains over a 6-month follow-up period. The results will advance our understanding of clinical research issues related to the concurrent treatment of alcohol and nicotine in dually-dependent patients. Finally, the proposed study will continue and extend the scope of our ongoing research program designed to evaluate the joint effects of behavioral and pharmacological interventions for substance dependence.