SCREENING MEDICATIONS FOR COCAINE CESSATION & RELAPSE PREVENTION

可卡因依赖很难治疗。尽管有40多个对照双盲试验， 尚未确定药物对可卡因依赖有效。迄今为止，大多数试验采用了基线水平和可卡因使用严重程度方面的异质性样本。某些药物的有效性可能取决于基线可卡因使用情况。我们提出了一种创新的方法，指定基线禁欲状态先验，并测试是否这个变量缓和药物治疗和结果之间的关系。在这份修订后的申请中，我们选择了三种潜在的药物，这些药物在基线戒断和非戒断条件下存在令人信服的理由来检查不同的治疗效果。基于初步研究结果，我们假设，当在可卡因戒断基线上给药时，纳洛酮50 mg和左旋多巴/卡比多巴800/200 mg将显示出优于安慰剂的显著疗效，与“复发预防”机制一致。此外，我们假设，莫达非尼400 mg将显示出显着的疗效超过安慰剂时，基线可卡因非戒断，符合“戒断启动”机制。这个为期5年的项目从4周的基线阶段开始，包括动机访谈和激励策略，用于在寻求治疗的可卡因使用者中启动禁欲。研究的第二阶段包括一项为期12周的药物试验，比较了四种药物治疗条件（安慰剂、纳洛酮50 mg、左旋多巴/卡比多巴800/200 mg和莫达非尼400 mg），并根据基线戒断状态（戒断/非戒断）分层随机分配。治疗期间，所有受试者（N=200）将接受心理治疗和应急管理， 提高服药依从性，定期进行尿液筛查，每周三次。治疗后（3个月、6个月）将继续测量客观和自我报告的药物使用情况。评估组合将收集必要的数据，以探讨项目的次要目标，即，与实现初始戒断有关的因素以及不同药物促进可卡因戒断或预防复吸的可能治疗机制。分层多元回归分析将用于确定基线状态是否会调节药物治疗对结局的影响。对于显著相互作用，将绘制两个调节水平（戒断vs非戒断）下每种处理条件的回归斜率。该项目将通过确定对治疗最敏感的亚群和基线条件，为我们的P50药物开发研究计划做出贡献，从而提供独特的新的和有价值的信息，以指导未来的治疗决策。

Cocaine dependence is difficult to treat. Despite more than 40 controlled double-blind trials, no medication has yet been identified as effective for cocaine dependence. To date, most trials have employed heterogeneous samples in terms of baseline level and severity of cocaine use. The possibility exists that certain medications may be more or less effective depending on baseline cocaine use. We propose an innovative methodology that specifies baseline abstinence status a priori, and tests whether this variable moderates the relationship between pharmacotherapy and outcome. In this revised application we have selected three potential medications for which there exists a compelling rationale for examining differential treatment effects under baseline abstinent and nonabstinent conditions. Based on preliminary findings, we hypothesize that naltrexone 50 mg and levodopa/carbidopa 800/200 mg will show significant efficacy over placebo when administered on a baseline of cocaine abstinence, consistent with a "relapse prevention" mechanism. Further, we hypothesize that modafinil 400 mg will show significant efficacy over placebo when administered on a baseline of cocaine non-abstinence, consistent with an "abstinence initiation" mechanism. This 5-year project begins with a 4-week baseline phase involving motivational interviewing and incentive strategies for initiating abstinence in treatment-seeking cocaine users. The second phase of the study consists of a 12-week medication trial comparing four pharmacotherapy conditions (placebo, naltrexone 50mg, levodopa/carbidopa 800/200 mg, and modafinil 400 mg) with stratified random assignment to condition based on baseline abstinence status (abstinent/non-abstinent). During treatment all subjects (N=200) will receive psychotherapy and contingency management designed to enhance medication compliance, with urine screening conducted on a fixed, thrice-weekly schedule. Objective and self-reported drug use will continue to be measured after treatment (3-, 6-months). The assessment battery will capture data necessary to explore secondary aims of the projects, i.e., factors related to achievement of initial abstinence and possible treatment mechanisms by which different medications facilitate cocaine cessation or relapse prevention. Hierarchical multiple regression analyses will be used to determine whether baseline status moderates the effect of pharmacotherapy on outcome. For significant interactions, regression slopes for each treatment condition at the two levels of the moderator (abstinent vs non-abstinent) will be plotted. This project will contribute to our P50 medication development research program by identifying subpopulations and baseline conditions most responsive to treatment, thus providing unique new and valuable information to guide future treatment decision making.