PILOT STUDY--SELEGILINE FOR SMOKING CESSATION

我们建议对有抑郁症状的尼古丁依赖吸烟者(N=30)进行一项司来吉兰与安慰剂的安慰剂对照先导研究。有证据表明，儿茶酚胺在吸烟的奖赏和戒断效应中起着重要作用，而单胺氧化酶抑制剂(MAOIs)增强儿茶酚胺(即多巴胺、去甲肾上腺素)的功能可能有助于缓解尼古丁依赖吸烟者对尼古丁的渴望和戒断症状。因此，选择性MAO-B抑制剂司来吉兰可能有助于戒烟的药理辅助作用。这项拟议的研究将对尼古丁依赖型吸烟者进行为期6周的试验，比较司来吉兰(每天10毫克；n=15)和安慰剂(n=15)治疗戒烟的效果。在第一周开始的戒烟日期之前的两周内，受试者每天服用10毫克司来吉兰(5毫克，po，2次)或与之匹配的安慰剂(每天两次)。所有受试者都将接受每周简短的戒烟咨询，符合AHCPR戒烟指南。主要结果包括戒烟后1周(第2周)和终点(第6周)戒烟率，以及在试验的最后4周内持续戒烟。次要结果指标包括治疗保留、抑郁症状、尼古丁戒断症状、体重变化、血浆可替宁水平、呼出气一氧化碳(CO)水平和尿儿茶酚胺排泄量。比较组的数据分析将侧重于意向治疗样本，并将利用卡方2x2列联表计算戒烟率，使用重复测量方差分析(ANOVA)模型进行连续结果测量(即抑郁和尼古丁戒断评分、CC、血可替宁和尿儿茶酚胺)，以及使用Kaplan-Meir生存分析进行治疗保留。如果这项先导研究的结果看起来很有希望，那么这项先导研究的结果将被用来计算计划一项更大规模对照试验的效果大小。我们预测，在尼古丁依赖型吸烟者中，司来吉林在戒烟方面无论是在初级还是二级疗效指标上都优于安慰剂。

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.