Two Medications to Treat Cocaine and Alcohol Dependence

这项申请是一项为期5年的N1DA中心计划的一部分，该中心将专注于测试治疗可卡因依赖的创新药物疗法。与可卡因或酒精依赖相比，可卡因依赖合并酒精依赖时，可卡因使用量更高，精神病理更多，治疗保留率更低，预后更差。这个为期5年的项目将通过双盲、安慰剂对照、为期12周的试验来评估纳曲酮和双硫仑联合治疗可卡因依赖的疗效，方法是减少过度饮酒。一种是纳曲酮100毫克/天，另一种是250毫克/天。这两种药物在美国都是FDA批准的酒精依赖药物。这项研究将是一个4细胞设计(每个细胞52S)，其中两种药物将单独或联合给予，并与安慰剂进行比较。该项目建议在5年内将208名被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/安慰剂组中的一个。所有药物将与每周心理社会治疗的治疗访问一起给予。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/退伍军人管理局成瘾研究中心的物质滥用门诊治疗研究计划的一部分。在治疗试验之后，将在治疗后6个月和9个月后进行两次访问。在整个试验过程中，将获得每周一次的患者自我报告、每周两次的尿液筛查、每月的附属报告和肝酶数据。用药依从性将通过每周的药片计数和尿中核黄素的存在来监测。当研究结束时失明，将对接受积极药物治疗的SS进行二次用药依从性检查，方法是检查两个试验中的血液样本是否存在双硫兰和/或纳曲酮的代谢物--β-纳曲醇。将获得所有心理社会治疗过程的录音带，并随机选择一个小组进行临床医生依从性的独立评级。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-酒精依赖型SS患者的可卡因和酒精使用量。

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.