Impact of Smoking Cessation on Sleep

描述（由申请人提供）：由于许多原因，包括出现厌恶的戒断症状，绝大多数戒烟尝试以失败告终。鉴于持续吸烟对健康的影响，治疗无效导致发病率和死亡率大幅上升，造成巨大的财政和人力成本。通常报告的症状之一，睡眠障碍本身，可以作为许多其他症状的放大器，因为在其他医学条件和实验情况下的睡眠障碍已被发现会产生烦躁不安，思维困难和困倦。安非他酮是一种有效帮助戒烟的药物，它也有睡眠障碍，这是一种常见的自我报告的副作用，在戒烟者中患病率估计在30- 50%之间。同样，经皮尼古丁的使用也与睡眠障碍有关，尤其是在使用超过24小时的情况下。安非他酮和透皮尼古丁的联合治疗在近50%的病例中产生睡眠障碍，相比之下，20%的戒烟者使用安慰剂。世界上关于戒烟和客观测量睡眠障碍的文献基于不到80个研究对象。我们建议采用随机的四组设计，反复测量戒断和睡眠障碍，以评估男性和女性吸烟者在行为咨询联合安慰剂安非他酮和尼古丁贴片、活性安非他酮、活性安非他酮贴片或活性安非他酮和尼古丁贴片联合治疗后戒烟的效果。受试者将被跟踪12个月，以确定禁欲（通过过期空气CO确认）。研究设计的一个关键方面是使用更新的觉醒定义，这可能更准确地反映戒烟后睡眠中断的真实程度。具体目标是：1)在一个比迄今为止在睡眠实验室中研究的吸烟者总数更大的样本中，使用最先进的中枢和自主神经系统唤醒测量技术来表征戒烟对睡眠的影响；2)确定目前推荐的戒烟治疗对睡眠和睡眠障碍的影响；3)评价戒烟治疗对日间嗜睡和情绪的影响；4)评估困倦和情绪障碍对复发的影响。以下假设将被测试：1)戒烟将与睡眠紊乱、脑电图和睡眠中的自主觉醒增加以及睡眠期间交感神经-迷走神经平衡的相对转变有关；2)使用安非他酮和透皮尼古丁会导致睡眠障碍的进一步增加，超过戒烟所见；3)停药相关和治疗相关的睡眠障碍增加与日间嗜睡和负性情绪增加、日间表现下降呈正相关；4)与停药相关的睡眠障碍、白天嗜睡和负性情绪增加与12个月内复发呈正相关；5)药物治疗对戒烟戒断效应的负面影响女性大于男性。这个项目的结果对于开发有针对性的治疗方法尤其重要，这些治疗方法旨在改善睡眠中断，作为整体戒烟策略的一部分。

DESCRIPTION (provided by applicant): The vast majority of attempts to quit smoking end in failure due to many reasons including the presence of aversive withdrawal symptoms. Given the health consequences of continued smoking, treatment ineffectiveness leads to substantially elevated morbidity and mortality, with immense financial and human cost. One of the commonly reported symptoms, sleep disturbance by itself, can act as an amplifier of many of the other symptoms, as sleep disturbance in other medical conditions and in experimental situations has been found to produce dysphoria, difficulty thinking, and drowsiness. Bupropion, an agent effective in assisting smoking cessation, also has sleep disturbance as a commonly identified self-reported side effect with prevalence estimates of from 30-50 percent among quitting smokers. Likewise, the use of transdermal nicotine is associated with reported sleep disturbance, especially when used over 24 hours. Combination treatment of bupropion and transdermal nicotine has been shown to produce sleep disturbance in nearly 50 percent of cases, compared to 20 percent of quitting smokers using a placebo. The world' s literature on smoking cessation and objectively measured sleep disturbance is based on fewer than 80 subjects. We propose to utilize a randomized, four-group design with repeated measurements of withdrawal and sleep disturbance to evaluate the effect of smoking cessation following treatment with behavioral counseling in combination with either placebo bupropion and nicotine patch, active bupropion, active patch, or combined active bupropion and patch in male and female smokers. Subjects will be followed for a period of twelve months to determine abstinence (confirmed by expired-air CO). A key aspect of the research design is the use of newer definitions of arousal that may more accurately reflect the true extent of sleep disruption following smoking cessation. The specific aims are to: 1) characterize the effect of smoking cessation on sleep using state-of-the-art techniques in measurement of central and autonomic nervous system arousal, in a sample larger than the total number of smokers studied in sleep laboratories to date; 2) determine the impact of currently recommended smoking cessation treatments on sleep and sleep disturbance; 3) evaluate the impact of smoking cessation treatments on daytime sleepiness and mood; and, 4) assess the effect of sleepiness and mood disturbance on relapse. The following hypotheses will be tested: 1) Smoking cessation will be associated with disturbed sleep, increases in EEG and autonomic arousals from sleep, and a relative shift to sympathetico-vagal balance during the sleep period; 2) The use of bupropion and transdermal nicotine will lead to further increases in sleep disturbance over and above those seen with smoking cessation; 3) The cessation-related and treatment-related increases in sleep disturbance will be positively related to an increase in daytime sleepiness and negative mood, and decreased daytime performance; 4) The cessation-related increase in sleep disturbance, daytime sleepiness, and negative mood will positively correlate with relapse within twelve months; 5) The negative impacts of pharmacotherapy treatment for the withdrawal effects of smoking cessation will be greater in women than in men. The results of this project will be particularly important for the development of targeted treatment approaches designed to ameliorate sleep disruption as part of an overall smoking cessation strategy.