Developing Adaptive Interventions for Cocaine Cessation and Relapse Prevention

 描述（由申请人提供）：药物成瘾是一种慢性的、破坏性的、但可治疗的疾病，对于这种疾病，存在越来越多的循证干预措施，包括药物治疗和心理治疗。然而，药物成瘾治疗的一个核心原则是，没有一种治疗方法适合所有人;相反，治疗方法需要根据患者的特点和反应进行调整，以便最大限度地发挥作用。理想情况下，临床医生将确定一系列干预措施，这些干预措施在成瘾治疗的不同阶段（从戒断开始到预防复发）中效果最好。适应性治疗干预已成功地用于告知这一顺序的临床决策过程。对于可卡因使用障碍（CUD），目前可用于启动戒断的最有效的干预措施是使用应急管理（CM）程序的行为治疗。密集CM已被证明产生40%的初始可卡因戒断率，与所有其他形式的行为或药物治疗无法比拟，使其成为CUD的原型一线治疗。重要的是，最初禁欲的成就预示着未来的禁欲。对于临床医生来说，这些研究结果转化为一个简单的问题：我们能否通过有针对性的干预措施提高CM的响应率？拟议的序贯、多重分配、随机试验（SMART）将提供回答这一问题所需的数据。首先，我们将确定接受和承诺疗法（ACT）与CM结合是否会增加初始治疗反应率。我们假设4周ACT+CM治疗将产生比初始治疗结合标准药物咨询与CM（DC+CM）更高的戒断率。ACT+CM对经验性回避和奖励敏感性的主要治疗机制的假设协同作用将分别进行检查。其次，对于初始治疗无反应的患者，我们将研究多巴胺靶向药物治疗是否是一种有效的增强策略。具体而言，我们假设，相对于涉及持续DC和/或安慰剂的治疗组合，持续ACT+CM治疗与左旋多巴-卡比多巴增强在促进禁欲方面将是最有效的。第三，对于对初始治疗有反应的患者，我们将评估与DC+CM相比，ACT+CM继续治疗预防复发的相对获益。ACT强调基于内在激励价值观的目标导向行动，因此预计将是一种更有效的干预措施，用于延长强化CM初始治疗后的禁欲持续时间。总之，该II期（PA-13-078）项目的结果应支持关于进一步III期确证性研究的Go/No Go决定。该项目的主要目的是解决一个重要的NIDA研究优先事项，并有可能显着影响我们如何定制治疗CUD，以最大限度地提高成果。

 DESCRIPTION (provided by applicant): Drug addiction is a chronic, devastating, but treatable disorder, for which there exists a growing armamentarium of evidence-based interventions, including pharmacotherapies and psychotherapies. A core principle of drug addiction treatment, however, states that no single treatment is appropriate for everyone; rather, treatments need to be adjusted based on patient characteristics and response in order to be maximally effective. Ideally, clinicians would identify a sequence of interventions that works best across different stages of addiction treatment, from abstinence initiation to relapse prevention. Adaptive treatment interventions have been used successfully to inform this sequential clinical decision-making process. For cocaine use disorders (CUD), the most potent intervention currently available for initiating abstinence is behavior therapy using contingency management (CM) procedures. Intensive CM has been shown to produce initial cocaine abstinence rates of 40%, unmatched by all other forms of behavioral or pharmacological treatment, making it a prototypical first-line therapy for CUD. Importantly, achievement of initial abstinence predicts future abstinence. For the clinician, these research findings translate into a straightforward question: Can we drive CM response rates even higher with targeted adjunctive interventions? The proposed sequential, multiple assignment, randomized trial (SMART) will provide the data needed to answer this question. First, we will determine whether Acceptance and Commitment Therapy (ACT) in combination with CM increases initial treatment response rates. We hypothesize that four weeks of treatment with ACT+CM will produce higher abstinence rates than initial treatment combining standard Drug Counseling with CM (DC+CM). The hypothesized synergism of ACT+CM on primary treatment mechanisms of experiential avoidance and reward sensitivity, respectively, will be examined. Second, for patients who do not respond to initial treatment, we will examine whether dopamine-targeted pharmacotherapy is an effective augmentation strategy. Specifically, we hypothesize that continued ACT+CM treatment with levodopa-carbidopa augmentation will be most effective in promoting abstinence relative to treatment combinations involving continued DC and/or placebo. Third, for patients who respond to initial treatment, we will assess the relative benefit of continued treatment with ACT+CM, as compared to DC+CM, to prevent relapse. ACT emphasizes goal-directed actions based on values that are intrinsically motivating, and is thereby expected to be a more effective intervention for extending the duration of abstinence following initial treatment with intensive CM. In summary, results from this Stage II (PA-13-078) project should support a Go/No Go decision about further Phase III, confirmatory studies. The primary aims of this project address an important NIDA research priority and have the potential to significantly impact how we tailor treatment of CUD to maximize outcomes.