Two Medications to Treat Cocaine and Alcohol Dependence

这项申请是N1DA中心5年计划的一部分，该中心将专注于测试治疗可卡因依赖的创新药物疗法。可卡因依赖合并酒精依赖与单独的可卡因依赖或酒精依赖相比，可卡因使用水平更高，精神病理更严重，治疗效果更差，预后更差。这个为期5年的项目将通过一项为期12周的双盲、安慰剂对照试验来评估纳曲酮和双硫仑联合使用通过减少过量饮酒来治疗可卡因依赖的疗效。一种药物是100毫克/天纳曲酮，另一种是250毫克/天双硫仑。这两种药物都是美国fda批准的治疗酒精依赖的药物。该研究将采用4细胞设计（每个细胞52s），其中两种药物将单独或联合使用，并与安慰剂进行比较。该项目建议在5年的时间里，随机抽取208名在DSM-IV中诊断为可卡因和酒精依赖的寻求治疗的Ss，将其分为四种药物/安慰剂组。所有的药物治疗都将与每周的心理治疗一起进行。我们将使用的行为干预是认知行为应对技能疗法（CBT）和药物管理。所有Ss将在宾夕法尼亚大学治疗研究中心（TRC）接受为期12周的治疗。TRC是宾夕法尼亚大学/退伍军人事务部成瘾研究中心的一个药物滥用门诊治疗研究项目。在治疗试验之后，将在治疗开始后6个月和9个月进行两次访问。在整个试验过程中，每周患者自我报告、每周两次尿液筛查、每月侧支报告和肝酶数据将被获取。药物依从性将通过每周药片计数和尿液中核黄素的存在来监测。在研究结束时，当盲法被打破时，将对接受活性药物治疗的Ss进行第二次药物依从性检查，通过检查两个试验中的血液样本是否存在双硫仑和/或-纳曲醇（纳曲酮的代谢物）。将获得所有心理治疗过程的录音带，并随机选择一个亚组对临床医生的依从性进行独立评分。治疗过程将通过动机（URICA）、治疗联盟（WAI）和应对技能获得（ASRPT）进行评估。总之，我们将尝试确定联合用药方案是否可以减少可卡因酒精依赖患者的可卡因和酒精使用。

This application is part of a 5-year proposal for a N1DA Center that will focus on testing innovative pharrrnacotherapies for the treatment of cocaine dependence. Cocaine dependence when complicated by alcohol dependence has been associated with higher levels of cocaine use, more psychopathology, poorer retention in treatment, and a worse prognosis than either cocaine or alcohol dependence alone. This 5-year project will evaluate in a double-blind, placebo-controlled, 12-week trial the efficacy of the combination of naltrexone and disulfiram for treating cocaine dependence by reducing excessive alcohol drinking. One medication will be 100 mg/day naltrexone and the other will be 250 mg/day disulfiram. Both medications are FDA-approved in the US for alcohol dependence. The study will be a 4-cell design (52Ss per cell) where each of the two medications will be given alone, or in combination, and compared to placebo. The project proposes to randomize over a 5-year period, 208 treatment-seeking Ss with a DSM-IV diagnosis of cocaine and alcohol dependence to one of four medication/placebo groups. All medications will be given in conjunction with weekly therapy visits of psychosocial treatment. The behavioral intervention we will use is Cognitive Behavioral Coping Skills Therapy (CBT) with medication management. All Ss will receive their treatment over a 12-week period at the University of Pennsylvania Treatment Research Center (TRC)--a substance abuse outpatient treatment research program that is part of the Penn/VA Center for Studies of Addictions. Following the treatment trial, there will be two visits at 6 and 9 months post-treatment entry. Weekly patient self-reports, twice-weekly urine screens, monthly collateral reports and liver enzyme data will be obtained throughout the trial. Medication compliance will be monitored by weekly pill counts and the presence of riboflavin in the urine. When the blind is broken at the end of the study, a secondary medication compliance check will be done for Ss who received active medication by examining two in-trial blood specimens for the presence of disulfiram and/or beta-naltrexol a metabolite of naltrexone. Audiotapes of all psychosocial treatment sessions will be obtained and a subgroup will be randomly selected for independent ratings of clinician adherence. Therapeutic process will be assessed with motivation (URICA), therapeutic alliance (WAI), and acquisition of coping skills (ASRPT). In sum, we will attempt to determine whether a combined medication regimen can reduce both cocaine and alcohol use in cocaine-alcohol dependent Ss.