Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

描述（由申请人提供）：该项目回答了过去十年中许多突出但大部分未被回答的呼吁，即解决精神健康障碍患者，特别是重度抑郁症（MDD）患者的烟草依赖问题。超过43%的重度抑郁症患者每天吸烟，他们更有可能大量吸烟，表现出更大的烟草依赖，更严重的戒断症状，并且比没有重度抑郁症的吸烟者戒烟率更低。由于几乎所有的随机临床试验都将这些吸烟者排除在外，因此对可能优化重度抑郁症吸烟者戒烟的治疗策略知之甚少。我们对42项随机临床试验（rct）进行了荟萃分析，其中包括近3000名既往重度抑郁症吸烟者，因为这些数据是常规收集的，并为当前或近期重度抑郁症患者的潜在治疗方法提供了见解。结果表明，CBT情绪管理（CBT MM）和伐尼克兰单独与短期戒断有最强的相关性。伐尼克兰与长期禁欲也有最强的联系。行为激活（BA）比CBT MM更容易管理和患者更容易理解，因此可以增强技能获得/保留和长期戒断。BA的目标是通过减少逃避、戒断和不活动的模式，增加对奖励活动的参与，这是患有重度抑郁症的吸烟者的一个问题，他们发现吸烟特别有益，并且比许多其他传统的奖励活动更喜欢吸烟。BA和varenicline联合治疗对于当前或近期重度抑郁症吸烟者的长期戒断率有很大的潜力，因为它解决了可能维持其烟草依赖的独特心理因素。该双盲、安慰剂对照、随机试验将评估BA联合伐尼克兰治疗当前或最近（过去一年）重度抑郁症吸烟者的烟草依赖的疗效。630名至少有中度抑郁症状的每日吸烟者（5支/天）将被随机分组，接受为期12周的四种治疗之一：1)标准行为戒烟治疗(ST) +安慰剂；2) BA联合ST (BA) +安慰剂；3) ST +伐尼克兰；或4)BA +伐尼克兰。BA和ST都将分为八个1小时的课程，前四周每周进行一次，后八周每两周进行一次。随机分组将根据临床地点（Northwestern， PENN）、性别和抑郁症状严重程度（中度vs重度）进行分层。主要结果将是在戒烟后24周一氧化碳（CO）验证的7天点流行戒断。其他目标包括评估伐尼克兰组和安慰剂组之间的不良事件发生率，并测试快感缺乏、认知功能（注意力和记忆）、香烟奖励价值、渴望和戒断对治疗效果的中介作用。这将是在这一人群中进行的首个充分有力的BA戒烟试验；首个评估伐尼克兰在重度抑郁症吸烟者社区样本中的随机对照试验；也是第一个评估这两种治疗的主要效果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.