A Sequenced Behavioral and Medication Intervention for Cocaine Dependence

描述(申请人提供)：这项申请将是首批测试顺序治疗策略的研究之一，在该策略中，行为干预将增加以多巴胺释放为目标的药物，以提高仅对行为治疗无效的个人的治疗反应。此外，还将进行分析，以确定与行为干预反应和序贯治疗策略相关的重要认知和语言过程。心理社会和行为干预是成瘾治疗的基石。我们的研究小组已经证明，用PET 11C-雷氯普利置换范例测量的多巴胺传递缺陷预示着对包括应急管理(CM)在内的行为治疗计划的不良反应。其他研究表明，用促进单胺类功能的药物来加强以CM为基础的行为疗法比单独使用任何一种疗法都能产生更好的结果。这些发现表明，识别对传统行为疗法没有反应的个体，并通过为促进多巴胺传递而量身定做的干预措施来加强这些治疗，可能对提高它们的整体疗效特别有效。在现有的药物中，兴奋剂能最直接、最有效地促进多巴胺的释放，并能显著改善认知和行为功能。我们小组进行的一项包括混合苯丙胺盐缓释(MAS-ER)的试点研究表明，一个包括兴奋剂激动剂替代策略的方案可能对促进严重可卡因依赖患者的戒断有效。因此，我们提出了一个第二阶段的治疗发展试验，在这个试验中，155名寻求治疗的可卡因依赖参与者将接受基于社区强化方法和应急管理(CRA+CM)的计算机辅助行为干预。前4周未能戒烟的患者将继续接受行为治疗(CRA+CM)，并被随机分配到行为治疗强化策略中，其中包括MAS-ER或安慰剂，为期10周的双盲试验。主要目的是验证这样一种假设，即在对行为疗法(CRA+CM)的初步试验没有反应的可卡因依赖患者中，与对照组CRA+CM/安慰剂相比，在增强行为治疗组CRA+CM/MAS-ER中有更大比例的患者将实现3周或更长时间的持续戒断。二级目标将描述与计算机辅助行为治疗相关的认知和语言过程，并测试每周使用可卡因和渴望、治疗保留和生活质量的综合治疗策略。我们还将探索单独接受行为治疗的参与者和接受联合治疗的参与者之间治疗反应的潜在调节者和调解者。这些变量将包括认知功能、复发预防技能的使用以及患者承诺语言的变化。

DESCRIPTION (provided by applicant): This application will be one of the first investigations to test a sequential treatment strategy in which a behavioral intervention will be augmented with a medication targeting dopamine release in order to boost treatment response among individuals not responding to the behavioral treatment alone. Further, analyses will be conducted to identify important cognitive and verbal processes associated with response to the behavioral intervention as well as the sequential treatment strategy. Psychosocial and Behavioral interventions are the cornerstone of addiction treatment. Our research group has demonstrated that deficient dopamine transmission, measured with the PET 11C-raclopride displacement paradigm, predicts poor response to a behavioral treatment program that included contingency management (CM). Other studies suggest that augmenting CM-based behavioral therapies with medications that boost mono-amine functioning can yield better outcomes than either treatment alone. These findings suggest that identifying individuals who do not respond to traditional behavioral therapies and enhancing these treatments with interventions tailored to boost dopamine transmission may be particularly effective for improving their overall efficacy. Among available medications, stimulants produce the most direct and potent augmentation of dopamine release and can significantly improve cognitive and behavioral functioning. A pilot study conducted by our group that included mixed amphetamine salts-extended release (MAS-ER) demonstrated that a regiment that included an agonist replacement strategy with stimulants maybe effective for promoting abstinence in severe cocaine dependent patients. Thus, we propose a Stage 2 treatment development trial in which 155 treatment- seeking cocaine dependent participants will receive a computer-assisted behavioral intervention based on the community reinforcement approach with contingency management (CRA + CM). Those who fail to achieve abstinence after the first 4 weeks will continue the behavioral treatment (CRA + CM) and be randomly assigned to a behavioral therapy enhancement strategy that will include either MAS-ER or placebo, over a 10- week double-blind trial. The Primary Aim is to test the hypothesis that among cocaine dependent patients who have failed to respond to an initial trial of behavioral therapy (CRA +CM), a greater proportion in the enhanced behavioral treatment arm CRA+CM/MAS-ER will achieve 3-weeks or more of continued abstinence compared to patients in the comparison group CRA+CM/PLACEBO. Secondary aims will characterize the cognitive and verbal processes associated with response to the computer-assisted behavioral treatment and test the combined treatment strategy on weekly cocaine use and craving, treatment retention, and quality of life. We will also explore potential moderators and mediators of treatment response across participants receiving the behavioral treatment alone and those receiving the combined treatment. These variables will include cognitive functioning, the use of relapse prevention skills, and changes in patient commitment language.