Pharmacotherapies: Efficacy, Mechanisms, and Algorithms

对于烟草依赖，有多种有效的药物治疗方法，但我们仍然不知道：哪种药物效果最好，如何最好地将个人与药物匹配，如何联合用药，以及药物如何达到它们的效果。这些知识差距的部分原因是缺乏对药物疗法的正面比较，包括较新的药物疗法(例如尼古丁含片)和药物疗法的组合。此外，临床医生和吸烟者没有基于科学的算法来指导这些药物的使用，因为对哪些药物在特定的吸烟者群体中最有效的了解有限。此外，还缺乏揭示药物疗法如何发挥作用的数据，这使得在理性的基础上开发新的药物疗法变得困难。参与者(n=1,520)将被随机分配到五种药物条件中的一种：尼古丁贴片、尼古丁含片、安非他酮、尼古丁贴片尼古丁含片和安非他酮尼古丁含片(n= 264/条件)和安慰剂对照条件(n=200)。将从参与者那里收集一套广泛的评估，包括：基因类型、个性、精神症状和诊断、生理和医疗状况、饮食、酒精使用/滥用、社会关系、生活质量、运动、吸烟、戒断症状、压力和尼古丁依赖。这些结构将使用心理测量学健全的问卷、结构化访谈、身体测试和生态瞬时评估(EMA)进行评估。评估将服务于三个重要目的：1)衡量治疗结果(例如，戒断、戒断 (2)根据个体差异(例如，性别、依赖程度)开发治疗匹配算法；以及(3)评估治疗效果的机制(例如，戒断抑制)。总而言之，该项目将提供迄今为止关于戒断药物疗法的相对有效性和作用机制的最佳证据，并将提供指导用药的算法。

There are multiple efficacious pharmacotherapies for tobacco dependence, yet we still do not know: which medications work best, how best to match individuals to medications, how to combine medications, and how medications achieve their effects. These knowledge gaps are due, in part, to a lack of head-to-head comparisons of pharmacotherapies, including newer pharmacotherapies (e.g., the nicotine lozenge) and combinations of pharmacotherapies. In addition, clinicians and smokers have no scientifically based algorithms to guide the use of these medications because of the limited knowledge about which medications are most efficacious in particular populations of smokers. Also lacking are data that reveal how pharmacotherapies work, making it difficult to develop new pharmacotherapies on a rational basis. Participants (n = 1,520) will be randomly assigned to one of five medication conditions: nicotine patch, nicotine lozenge, bupropion, nicotine patch + nicotine lozenge, and bupropion + nicotine lozenge (n= 264/condition) and a placebo control condition (n=200). An extensive set of assessments will be collected from participants including: genotypes, personality, psychiatric symptoms and diagnoses, physiologic and medical status, diet, alcohol use/abuse, social relations, quality of life, exercise, smoking, withdrawal symptoms, stress, and nicotine dependence. These constructs will be assessed using psychometrically sound questionnaires, structured interviews, physical tests, and ecological momentary assessment (EMA). Assessments will serve three vital purposes: 1) to measure treatment outcomes (e.g., abstinence, withdrawa symptoms, weight gain); 2) to develop treatment matching algorithms based on individual differences (e.g., gender, level of dependence); and 3) to assess mechanisms of treatment effects (e.g., withdrawal suppression). In sum, this project will produce the best evidence to date on relative efficacies and mechanisms of action of cessation pharmacotherapies, and will provide algorithms to guide medication use.