Combined Treatment for Cocaine-Alcohol Dependence

描述（由申请人提供）：寻求治疗的可卡因和酒精依赖患者预后不良。虽然没有唯一有效的药物，但药物和心理治疗相结合可能是有效的。被批准用于酒精依赖的纳曲酮（NTX），在高剂量（50毫克/天）下可能会阻断可卡因-酒精的奖励作用，但心理治疗背景是至关重要的。我们的初步研究表明，当与复发预防（RP）疗法和应急管理程序（CMP）联合使用时，NTX的潜在效用。我们建议进行一项大型、双盲、安慰剂对照、全因子研究，以检验RP + CMP联合NTX治疗可卡因酒精依赖的作用。可卡因酒精依赖门诊患者（N = 140）将被随机分配到NTX 100 mg/d或安慰剂联合两种心理治疗条件之一（RP或RP + CMP）。标准化的同意和摄入程序之后是单盲基线安慰剂周，然后是12周的试验，每周两次就诊。手动引导的RP治疗将每周提供60分钟的个人疗程。CMP将根据可卡因尿液筛查阴性和呼气酒精测试阴性结果加强戒断。药物依从性将通过核黄素和药丸计数进行监测。随访评估将在治疗结束后3、6、9和12个月进行。主要疗效变量将是药物使用（即尿液筛查、时间线随访方法、附带信息提供者、肝酶变化）和保留（即参加的会议次数、退出的时间）。次要变量包括成瘾严重程度和不良事件测量。第三组变量将作为治疗结果的可能预测因素进行测试。这些指标包括动机、自我效能、药物依从性、血清6- β纳曲醇水平、渴望、酒精家族史和依赖程度。功率足以测试主要假设，即NTX 100毫克/天与RP + CMP将减少可卡因和酒精的使用。其次，我们将：(1)检查结果变异性作为一系列潜在预测因子上个体差异的函数；(2)采用创新的多项选择测量策略评估可卡因和酒精的相对强化作用；(3)研究治疗和随访期间可卡因与酒精使用的关系。

DESCRIPTION (provided by applicant): Treatment seeking patients who are cocaine and alcohol dependent have poor prognosis. While there are no uniquely effective medications, combined pharmaco- and psychotherapy may prove efficacious. Naltrexone (NTX), approved for alcohol dependence, may block cocaine-alcohol rewarding effects at higher doses (> 50 mg/d) but psychotherapeutic context is critical. Our preliminary work indicates potential utility of NTX when combined with Relapse Prevention (RP) therapy and Contingency Management Procedures (CMP). We propose a large, double-blind, placebo-controlled, full factorial study to examine the role of RP + CMP combined with NTX for treatment of cocaine-alcohol dependence. Cocaine-alcohol dependent outpatients (N = 140) will be randomly assigned to NTX 100 mg/d or placebo combined with one of two psychotherapy conditions (RP or RP + CMP). Standardized consent and intake procedures will be followed by a single-blind baseline placebo week and then a 12 week trial with twice weekly visits. Manual-guided RP therapy will be delivered weekly in 60-minute individual sessions. CMP will reinforce abstinence based on cocaine-negative urine screens and negative breath alcohol test results. Medication adherence will be monitored with riboflavin and pill counts. Follow-up assessments will be conducted at 3, 6, 9, and 12 months after treatment termination. Primary efficacy variables will be measures of substance use (i.e., urine screens, Time-Line Follow-Back methods, collateral informants, change in liver enzymes) and retention (i.e., number of sessions attended, time to dropout). Secondary variables will include addiction severity and adverse event measures. A third set of variables will be tested as possible predictors of therapeutic outcomes. These include measures of motivation, self-efficacy, medication compliance, serum 6-beta naltrexol levels, craving, family history of alcohol problems, and severity of dependence. Power is sufficient to test the main hypothesis that NTX 100 mg/d with RP + CMP will reduce cocaine and alcohol use. Secondarily we will: (1) examine outcome variability as a function of individual differences on a range of potential predictors; (2) evaluate relative reinforcement of cocaine and alcohol using an innovative multiple choice measurement strategy; and (3) examine the relationship between cocaine and alcohol use during treatment and follow-up.