PILOT STUDY--SELEGILINE FOR SMOKING CESSATION

我们建议对伴有抑郁症状的尼古丁依赖吸烟者（N=30）进行安慰剂对照试验。有证据表明儿茶酚胺在吸烟的奖励和戒断效应中起重要作用，单胺氧化酶抑制剂（MAOIs）增强儿茶酚胺（即多巴胺，去甲肾上腺素）的功能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MAO-B抑制剂selegiline可能有助于作为戒烟的药理学辅助。拟议的研究将在尼古丁依赖吸烟者中进行为期6周的试验，比较斯来吉兰（每天10毫克，n=15）和安慰剂（n=15）治疗对戒烟效果的影响。在第1周开始的“戒烟日”之前的两周内，受试者将被诱导服用10毫克/天的selegiline（每次5毫克）或匹配的安慰剂（每天两次）。所有受试者将接受与AHCPR戒烟指南一致的每周简短戒烟咨询。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，以及试验最后四周的持续戒烟情况。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、呼气中一氧化碳（CO）水平和尿儿茶酚胺排泄。比较各组的数据分析将侧重于意向治疗样本，并将使用卡方2 × 2列联表来衡量戒烟率，使用重复测量方差分析（ANOVA）模型来衡量连续结果（即抑郁和尼古丁戒断评分、CC、血浆可替宁和尿儿茶酚胺），以及Kaplan-Meir生存分析来衡量治疗保留情况。如果该初步研究的结果显示有希望，该初步研究的结果将用于计算计划更大规模对照试验的效应量。我们预测，对于尼古丁依赖的吸烟者，在主要和次要结局指标上，斯来吉兰的戒烟效果都优于安慰剂。

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.