Developing Adaptive Interventions for Cocaine Cessation and Relapse Prevention

 描述(申请人提供)：毒瘾是一种慢性的、破坏性的、但可治疗的疾病，有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每个人；相反，治疗需要根据患者的特征和反应进行调整，以便发挥最大的效果。理想情况下，临床医生将确定一系列干预措施，最有效地跨越成瘾治疗的不同阶段，从戒断开始到复发预防。适应性治疗干预已被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)，目前可用于启动戒烟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，是所有其他形式的行为或药物治疗所无法比拟的，使其成为CUD的典型一线治疗方法。重要的是，最初禁欲的成功预示着未来的禁欲。对于临床医生来说，这些研究结果转化为一个直截了当的问题：我们是否可以通过有针对性的辅助干预来进一步提高CM的应答率？拟议的序贯、多重分配、随机试验(SMART)将提供回答这个问题所需的数据。首先，我们将确定接受与承诺疗法(ACT)与CM相结合是否提高了初始治疗应答率。我们假设，四周的ACT+CM治疗将产生比最初的结合标准药物咨询和CM(DC+CM)治疗更高的戒断率。本研究将检验ACT+CM在经验回避和奖赏敏感性初级处理机制上的假设协同效应。第二，对于对初始治疗无反应的患者，我们将检查多巴胺靶向药物治疗是否是一种有效的增强策略。具体地说，我们假设，与继续使用DC和/或安慰剂的联合治疗相比，继续ACT+CM加左旋多巴-卡比多巴强化治疗将在促进戒断方面最有效。第三，对于对初步治疗有反应的患者，我们将评估与DC+CM相比，继续使用ACT+CM预防复发的相对益处。ACT强调基于内在激励的价值观的目标导向行动，因此有望成为一种更有效的干预措施，以延长强化CM初步治疗后的禁欲持续时间。总而言之，这个第二阶段(PA-13-078)项目的结果应该支持关于进一步的第三阶段验证性研究的通过/不通过的决定。该项目的主要目标是解决NIDA的一个重要研究重点，并有可能显著影响我们如何量身定做CUD的治疗以最大化结果。

 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.