Two Medications to Treat Cocaine and Alcohol Dependence

该应用程序是N1 DA中心5年提案的一部分，该中心将专注于测试用于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时，与可卡因使用水平较高、精神病理学程度较高、治疗保留较差以及预后较差相比，可卡因或酒精依赖单独存在。这个为期5年的项目将在一项为期12周的双盲、安慰剂对照试验中评估纳曲酮和双硫仑联合使用通过减少过度饮酒来治疗可卡因依赖的疗效。一种药物将是100 mg/天的纳洛酮，另一种药物将是250 mg/天的双硫仑。这两种药物在美国都是FDA批准的酒精依赖药物。本研究将采用4-细胞设计（每个细胞52 S），其中两种药物将单独或联合给药，并与安慰剂进行比较。该项目建议在5年内将208名DSM-IV诊断为可卡因和酒精依赖的寻求治疗的SS随机分配到四个药物/安慰剂组之一。所有药物将与每周一次的心理治疗访视结合使用。我们将使用的行为干预是认知行为应对技能疗法（CBT）与药物管理。所有学生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/VA成瘾研究中心的一个药物滥用门诊治疗研究项目。治疗试验后，将在治疗入组后6个月和9个月进行两次访视。在整个试验期间，将获得每周一次的患者自我报告、每周两次的尿液筛查、每月一次的附带报告和肝酶数据。将通过每周药丸计数和尿液中核黄素的存在来监测药物依从性。当研究结束时揭盲时，将通过检查两份试验期间血液标本中是否存在双硫仑和/或β-纳曲酮（纳曲酮的代谢产物），对接受活性药物治疗的受试者进行二次药物依从性检查。将获得所有心理社会治疗会话的录音带，并随机选择一个亚组对临床医生依从性进行独立评级。治疗过程将通过动机（URICA）、治疗联盟（阿威）和获得应对技能（ASRPT）进行评估。总之，我们将试图确定联合用药方案是否可以减少可卡因和酒精依赖的SS可卡因和酒精的使用。

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.