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）：尼古丁替代疗法、安非他酮和最近的伐尼克兰对于尼古丁依赖的药物治疗的功效已经确定。尼古丁依赖药物治疗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，根据定义，这代表了一种“一刀切”的治疗应用方法。虽然这在治疗评估的初始阶段是适当的，但联合治疗提高疗效水平高于单独治疗的潜力通常尚未被探索。本申请的重点是评估伐尼克兰和安非他酮的联合作用，这两种药物本身都是 FDA 批准的戒烟药物。两者都在随机临床试验中显示出对戒烟和治疗尼古丁戒断症状的有效性。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、适度抑制多巴胺再摄取和尼古丁拮抗作用。伐尼克兰主要作为 VTA 中 1422 尼古丁胆碱能受体的部分激动剂，并相对于尼古丁而言，在伏隔核中提供减弱的多巴胺释放。伐尼克兰的关键试验结果表明，它比单独使用安非他酮更有效。然而，有多种推理表明这些药物的组合可能比单独使用伐尼克兰更有效。两种药物作用机制的合理差异及其作用强度的差异表明，联合使用这些药物将影响被认为对戒烟重要的更广泛的生物靶标，特别是可能影响和增强多巴胺能通路的反应。本研究是一项随机、双盲临床试验，旨在评估伐尼克兰、伐尼克兰加安非他酮的疗效 安慰剂对戒烟、尼古丁戒断、负面情绪、渴望和吸烟满意度的影响。我们还将评估治疗结果与认知表现测量之间的关系。我们假设，与单独使用伐尼克兰治疗的吸烟者相比，联合使用这两种药物治疗的吸烟者戒烟的频率明显更高，需要更长的时间才能复发，并且尼古丁戒断症状、负面情绪、渴望和吸烟强化的水平显着降低。继续开发针对多个生物系统的联合疗法将提高任何一个个体戒烟尝试的成功机会，并有可能为未来针对个体特定特征（即共病史、遗传学等）定制治疗方案的研究提供信息。

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