PILOT STUDY--SELEGILINE FOR SMOKING CESSATION

我们建议进行一项安慰剂对照的先导性研究，比较司来吉兰与安慰剂治疗伴有抑郁症状的尼古丁依赖性吸烟者（N=30）。有证据表明，儿茶酚胺在吸烟的奖励和戒断效应中具有重要作用，并且增强儿茶酚胺（即多巴胺、去甲肾上腺素）功能的单胺氧化酶抑制剂（MAOI）可能有助于减轻尼古丁依赖吸烟者的尼古丁渴望和戒断症状。因此，选择性单胺氧化酶-B抑制剂司来吉兰可能有助于作为一种药物辅助戒烟。拟议的研究将是一项在尼古丁依赖性吸烟者中进行的为期6周的试验，将比较司来吉兰（每日10 mg; n=15）与安慰剂（n=15）治疗对戒烟结果的影响。受试者将在第1周开始时的“戒烟日期”之前的两周内接受10 mg/天的司来吉兰（5 mg po bid）或匹配的安慰剂（每日两次）。所有受试者将接受每周一次的简短戒烟咨询，与AHCPR戒烟指南一致。主要结局指标包括戒烟后1周（第2周）和终点（第6周）戒烟率，以及试验最后4周期间的持续戒烟率。次要结局指标包括治疗保留、抑郁症状、尼古丁戒断症状、体重变化、血浆可替宁水平、呼气一氧化碳（CO）水平和尿儿茶酚胺排泄。比较组的数据分析将集中于意向治疗样本，并将使用卡方2x2列联表进行戒烟率分析，使用重复测量方差分析（ANOVA）模型进行连续结局测量（即抑郁和尼古丁戒断评分、CC、血浆可替宁和尿儿茶酚胺），使用Kaplan-Meir生存分析进行治疗保留。如果该初步研究的结果显示有希望，则该初步研究的结果将用于计算效应量，以计划更大的对照试验。我们预测，司来吉兰在尼古丁依赖吸烟者戒烟的主要和次要结局指标方面均上级安慰剂。

We are proposing a placebo-controlled pilot study of selegiline versus placebo for nicotine dependent smokers (N=30) with depressive symptoms. There is evidence that catecholamines have an important role in the rewarding and withdrawal effects of tobacco smoking, and monoamine oxidase inhibitors (MAOIs) which augment catecholamine (i.e. dopamine, norepinephrine) function may be helpful in attenuating nicotine craving and withdrawal symptoms in nicotine dependent smokers. Thus, the selective MAO-B inhibitor selegiline may be helpful as a pharmacologic adjunct for smoking cessation. The proposed study would be a 6 week trial in nicotine-dependent smokers which will compare selegiline (10 mg daily; n=15) versus placebo (n=15) treatments on smoking cessation outcomes. Subjects would be inducted onto 10 mg/day of selegiline (5 mg po bid) or matching placebo (twice daily) over a two week period prior to the "quit date" at the beginning of Week 1. All subjects would receive brief weekly sessions of smoking cessation counseling consistent with AHCPR smoking cessation guidelines. The primary outcome measures include 1 week post-quit (Week 2) and endpoint (Week 6) smoking abstinence rates, and continuous smoking abstinence during the last four weeks of the trial. Secondary outcomes measures include treatment retention, depressive symptoms, nicotine withdrawal symptoms, weight change, plasma cotinine levels, expired breath carbon monoxide (CO) levels and urinary catecholamine excretion. Data analyses to compare groups will focus of an intention-to-treat sample and will utilize Chi square 2x2 contingency tables for smoking abstinence rates, repeated measures analysis of variance (ANOVA) models for continuous outcome measures (i.e. depression and nicotine withdrawal ratings, CC, plasma cotinine and urinary catecholamines) and Kaplan-Meir survival analysis for treatment retention. Results from this pilot study would be used to calculate an effect size for planning a larger controlled trial if results from this pilot study appear promising. We predict that selegiline will be superior to placebo for smoking cessation in nicotine dependent smokers on both primary and secondary outcome measures.