Pharmacotherapies: Efficacy, Mechanisms, and Algorithms

有多种有效的药物治疗烟草依赖，但我们仍然不知道：哪些药物效果最好，如何最好地匹配个人的药物，如何联合收割机药物，以及药物如何实现其效果。这些知识差距的部分原因是缺乏对药物疗法的头对头比较，包括较新的药物疗法（例如，尼古丁锭剂）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，因为关于哪些药物在特定吸烟人群中最有效的知识有限。此外，还缺乏揭示药物疗法如何发挥作用的数据，这使得很难在合理的基础上开发新的药物疗法。受试者（n = 1，520）将被随机分配到五种药物治疗条件之一：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= 1，520）。 264/条件）和安慰剂对照条件（n=200）。将从受试者中收集一组广泛的评估，包括：基因型、个性、精神症状和诊断、生理和医学状况、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问卷，结构化访谈，物理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）测量治疗结果（例如，禁欲，戒断 症状，体重增加）; 2）开发基于个体差异的治疗匹配算法（例如，性别、依赖程度）;和3）评估治疗效果的机制（例如，戒断抑制）。总之，该项目将产生迄今为止关于戒烟药物治疗的相对疗效和作用机制的最佳证据，并将提供指导药物使用的算法。

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.