Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

描述(由申请人提供)：该项目回应了过去十年中许多突出但基本上未得到回应的呼吁，以解决患有精神健康障碍，特别是严重抑郁障碍(MDD)的人对烟草的依赖问题。超过43%的患有MDD的人是日常吸烟者，他们比没有MDD的吸烟者更有可能吸烟严重，表现出更大的烟草依赖，遭受更严重的戒断，戒烟率更低。对于可能优化MDD吸烟者戒烟的治疗策略，人们知之甚少，因为几乎所有的随机临床试验都排除了这些吸烟者。我们对42项随机临床试验(RCT)进行了荟萃分析，这些试验涵盖了近3000名既往患有MDD的吸烟者，因为这些数据是常规收集的，并为目前或最近患有MDD的患者提供了潜在的治疗方法。结果表明，CBT情绪管理(CBT MM)和varenicline分别与短期戒断有最强的相关性。瓦伦尼克林与长期禁欲的关联性也最强。行为激活(BA)比CBT MM更易于管理和患者理解，因此可以增强技能的获得/保持和长期戒断。BA的目标是通过减少回避、戒烟和不活动的模式，增加对奖励活动的参与，这是患有MDD的吸烟者的一个问题，他们认为吸烟特别有益，并比许多其他传统的奖励活动更喜欢吸烟。BA和varenicline的联合治疗有很大的潜力提高目前或最近患有MDD的吸烟者的长期戒烟率，因为它解决了可能维持他们对烟草依赖的独特心理因素。这项拟议的双盲、安慰剂对照、随机试验将评估BA联合varenicline治疗当前或最近(过去一年)MDD吸烟者的烟草依赖的疗效。630名每天(e5支/天)至少有中度抑郁症状的吸烟者将随机接受四种治疗之一的12周治疗：1)标准行为戒断治疗(ST)+安慰剂；2)BA合并ST(BA)+安慰剂；3)ST+varenicline；或4)BA+varenicline。BA和ST将在8个1小时的疗程中进行，前4周每周一次，最后8周每两周进行一次。随机化将根据临床地点(西北，宾夕法尼亚)、性别和抑郁症状的严重程度(中度与重度)进行分层。主要结果将是在戒烟后24周内一氧化碳(CO)证实的7天点戒酒盛行率。其他目标包括评估varenicline和安慰剂之间的不良事件发生率，以及测试快感缺失、认知功能(注意力和记忆力)、香烟奖励价值以及渴望和戒烟对治疗效果的调节作用。这将是BA在这一人群中戒烟的第一次动力充足的试验；第一次在患有MDD的吸烟者的社区样本中评估varenicline的随机对照试验；以及第一次评估这两种疗法的主要和综合效果的随机对照试验。

DESCRIPTION (provided by applicant): This project answers many prominent but largely unanswered calls over the last decade to address tobacco dependence in persons with mental health disorders, especially major depressive disorder (MDD). Upwards of 43% of persons with MDD are daily smokers who are more likely to smoke heavily, show greater tobacco dependence, suffer more severe withdrawal, and experience lower quit rates than smokers without MDD. Very little is known about treatment strategies that might optimize smoking cessation for smokers with MDD because almost all randomized clinical trials have excluded these smokers. We conducted a meta-analysis of 42 randomized clinical trials (RCTs) comprising nearly 3000 smokers with past MDD given that these data were routinely collected and offer insight into potential treatment approaches for patients with current or recent MDD. Results showed that CBT mood management (CBT MM) and varenicline individually had the strongest associations with short-term abstinence. Varenicline also had the strongest association with long-term abstinence. Behavioral activation (BA) is simpler to administer and easier for patients to understand than CBT MM and therefore may enhance skill acquisition/retainment and long-term abstinence. The goal of BA is to increase engagement in rewarding activities, a problem for smokers with MDD who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of avoidance, withdrawal, and inactivity. Combination treatment with BA and varenicline has great potential to improve long- term abstinence rates for smokers with current or recent MDD because it addresses the unique psychological factors that may maintain their tobacco dependence. This proposed double-blind, placebo-controlled, randomized trial will evaluate the efficacy of BA plus varenicline for treating tobacco dependence in smokers with current or recent (past year) MDD. Six hundred and thirty daily (e5 cigarettes/day) smokers with at least moderate depressive symptoms will be randomized to receive 12 weeks of one of four treatments: 1) Standard behavioral cessation treatment (ST) + placebo; 2) BA integrated with ST (BA) + placebo; 3) ST + varenicline; or 4) BA + varenicline. Both BA and ST will be administered in eight 1-hour sessions, occurring weekly for the first four weeks and biweekly for the final eight weeks. Randomization will be stratified on clinical site (Northwestern, PENN), gender, and severity of depressive symptoms (moderate vs. severe). The primary outcomes will be carbon monoxide (CO) verified 7-day point prevalence abstinence at 24-weeks post-quit. Additional aims include assessing adverse event rates between varenicline and placebo arms, and testing for mediation of treatment effects by anhedonia, cognitive function (attention and memory), cigarette reward value, and craving and withdrawal. This will be the first adequately powered trial of BA for smoking cessation in this population; the first RCT to evaluate varenicline among a community sample of smokers with MDD; and the first RCT to assess the main and combined effects of these two treatments.