Effectiveness of Varenicline vs. Varenicline plus Bupropion for Smoking Cessation

伐尼克兰与伐尼克兰加安非他酮的戒烟效果对比

• 批准号: 8588300
• 负责人: PAUL MICHAEL CINCIRIPINI
• 金额: $ 54.63万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8588300
• 关键词: Abstinence; Affect; Agonist; Attenuated; Biological; Bupropion; Characteristics; Cholinergic Receptors; Clinical Trials Design; Cognitive; Combined Modality Therapy; Dopamine; Double-Blind Method; Drug Combinations; Drug Industry; Effectiveness; Evaluation; FDA approved; Genetic; Health; Individual; Individual Differences; Mainstreaming; Measures; Moods; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Norepinephrine; Nucleus Accumbens; Outcome Measure; Pathway interactions; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacological Treatment; Placebos; Process; Property; Psychological reinforcement; Public Health; Randomized; Randomized Clinical Trials; Recording of previous events; Relapse; Relative (related person); Reporting; Research; Research Personnel; Second-Generation Antidepressive Agents; Smoke; Smoker; Smoking; Staging; Testing; Time; Treatment Efficacy; Treatment outcome; Withdrawal Symptom; Withholding Treatment; Work; biological systems; cognitive change; craving; depressive symptoms; improved; nicotine replacement; placebo controlled study; prevent; response; satisfaction; smoking cessation; success; treatment response; uptake; varenicline

DESCRIPTION (provided by applicant): The efficacy for the pharmacological treatment of nicotine dependence has been established for nicotine replacement therapies, bupropion and most recently, varenicline. The vast majority of research in the pharmacological treatment of nicotine dependence has focused on the evaluation of single medications in placebo controlled trials, which by definition represents a "one-size fits all" approach to the application of the treatment. While this is appropriate in the initial stages of treatment evaluation, the potential for combined treatments to raise the level of efficacy above individual treatments alone is often unexplored. The focus of this application is on the evaluation of the combined effects of varenicline and bupropion, both in their own right FDA approved medications for smoking cessation. Both have shown effectiveness in randomized clinical trials for smoking cessation and the treatment of nicotine withdrawal symptoms. Bupropion is an atypical antidepressant whose properties include inhibition of norepinephrine re-uptake, modest dopamine re-uptake inhibition and nicotine antagonist affects. Varenicline acts primarily as a partial agonist of the 1422 nicotine cholinergic receptor in the VTA and provides an attenuated release of dopamine in the nucleus accumbens, relative to nicotine. The results from the pivotal trials of varenicline showed it to be more effective than bupropion alone. However, there are several lines of reasoning to suggest that the combination of these drugs might be more effective than varenicline alone. Plausible differences in the mechanisms of action of the two drugs and differences in their intensity of action suggest that combining these medications, will affect a broader range of the biological targets among those identified as being important for smoking cessation, and in particular may effect and enhanced response in the dopaminergic pathways The present study is a randomized, double-blinded clinical trial designed to evaluate the efficacy of varenicline, varenicline plus bupropion and placebo on smoking cessation, nicotine withdrawal, negative affect, craving, and smoking satisfaction. We will also evaluate the relationship between treatment outcomes and measures of cognitive performance. We hypothesize that smokers treated with the combination of the two medications will be abstinent significantly more often, will take a longer time to relapse, and will report significantly lower levels of nicotine withdrawal symptoms, negative affect, craving and smoking reinforcement, than those treated with varenicline alone. Continuing to develop combination therapies that target multiple biological systems will improve the chances of success on any one individual smoking cessation attempt and has the potential to inform future research on tailoring treatments to particular characteristics of the individual (i.e. comorbid history, genetics, etc).

描述（由申请人提供）：已经确定了尼古丁依赖的药理学治疗的功效，用于尼古丁替代疗法，安非他酮，而最近，varenicline。尼古丁依赖的药理学治疗中的绝大多数研究都集中在安慰剂对照试验中对单一药物的评估，从定义上讲，该试验代表了一种“一定程度适合所有”方法。尽管这在治疗评估的初始阶段是适当的，但通常没有探索合并治疗以在单独治疗上提高疗效水平的潜力。该应用的重点是评估Varenicline和Bupropion的综合作用，均由其自身的FDA批准的戒烟药物。两者都在随机临床试验中表现出有效性，用于戒烟和治疗尼古丁戒断症状。安非他酮是一种非典型抗抑郁药，其特性包括抑制去甲肾上腺素再摄取，适度的多巴胺再摄取抑制和尼古丁拮抗剂的影响。 Varenicline主要充当VTA中1422个尼古丁胆碱能受体的部分激动剂，并相对于尼古丁提供了伏伏核中多巴胺的衰减释放。 Varenicline关键试验的结果表明，仅比安非他酮更有效。但是，有几条推理表明，这些药物的组合可能比单独的varenicline更有效。两种药物的作用机制以及它们的作用强度的差异表明，结合这些药物将影响更广泛的生物靶标，在被确定为对戒烟很重要的生物学靶标之间，尤其可能影响并可能影响并增强多巴胺能途径的反应，目前的研究是一项随机的临床范围，是一项随机的临床范围，并有效地构成了BBERTIAL的临床范围，并有效地进行了BBERING的范围。和安慰剂在戒烟，尼古丁戒断，负面影响，渴望和吸烟满意度上。我们还将评估治疗结果与认知表现措施之间的关系。我们假设，通过两种药物的组合治疗的吸烟者将更频繁地戒酒，将需要更长的时间复发，并且报告的尼古丁戒断症状，​​负面影响，渴望和吸烟增强的水平明显较低，而不是单独使用VarenicLine治疗的人。继续开发靶向多个生物系统的组合疗法将改善任何一个单独的戒烟尝试的成功机会，并有可能为未来的有关针对个体特定特征（即合并史，遗传学等）定制治疗的研究提供信息。

项目成果

An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use.

• DOI: 10.1111/add.14250
• 发表时间: 2018-04-21
• 期刊: Addiction (Abingdon, England)
• 作者: Cinciripini PM;Minnix JA;Green CE;Robinson JD;Engelmann JM;Versace F;Wetter DW;Shete S;Karam-Hage M
• 通讯作者: Karam-Hage M