A Sequenced Behavioral and Medication Intervention for Cocaine Dependence

描述（由申请人提供）：本申请将是测试序贯治疗策略的首批研究之一，其中将使用靶向多巴胺释放的药物增强行为干预，以提高对单独行为治疗无反应的个体的治疗反应。此外，将进行分析，以确定与行为干预以及序贯治疗策略相关的重要认知和言语过程。心理和行为干预是成瘾治疗的基石。我们的研究小组已经证明，缺乏多巴胺传输，测量与PET 11 C-雷氯必利位移范例，预测不良反应的行为治疗计划，包括应急管理（CM）。其他研究表明，用促进单胺功能的药物来增强基于CM的行为疗法可以产生比单独治疗更好的结果。这些研究结果表明，识别对传统行为疗法没有反应的个体，并通过针对促进多巴胺传递的干预措施来加强这些治疗，可能对提高其整体疗效特别有效。在现有的药物中，兴奋剂产生最直接和有效的多巴胺释放增加，可以显着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，包括兴奋剂激动剂替代策略的方案可能有效地促进重度可卡因依赖患者的戒断。因此，我们提出了第2阶段治疗开发试验，其中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。那些在前4周后未能实现禁欲的人将继续行为治疗（CRA + CM），并被随机分配到行为治疗增强策略，包括MAS-ER或安慰剂，为期10周的双盲试验。主要目的是检验以下假设：在对行为治疗（CRA +CM）的初始试验无效的可卡因依赖患者中，与对照组CRA+CM/安慰剂相比，强化行为治疗组CRA+ CM/MAS-ER中更大比例的患者将实现3周或更长时间的持续戒断。次要目标将描述与计算机辅助行为治疗反应相关的认知和言语过程，并测试每周可卡因使用和渴望，治疗保留和生活质量的联合治疗策略。我们还将探索单独接受行为治疗和接受联合治疗的参与者之间治疗反应的潜在调节剂和介导剂。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.