Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

描述（由申请人提供）：该项目回答了许多突出的，但在过去十年中基本上无人接听的电话，以解决精神健康障碍，特别是重度抑郁症（MDD）患者的烟草依赖问题。超过43%的MDD患者是每日吸烟者，他们更有可能大量吸烟，表现出更大的烟草依赖，遭受更严重的戒断，并且比没有MDD的吸烟者戒烟率更低。关于可能优化MDD吸烟者戒烟的治疗策略知之甚少，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，其中包括近3000名既往MDD吸烟者，因为这些数据是常规收集的，并为当前或近期MDD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禁欲有最强的关联。伐尼克兰也与长期禁欲有最强的联系。行为激活（BA）比CBT MM更容易管理，患者更容易理解，因此可以提高技能获得/保持和长期禁欲。BA的目标是通过减少回避、戒断和不活动的模式，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和伐尼克兰的联合治疗具有很大的潜力，可以提高目前或近期MDD吸烟者的长期戒烟率，因为它解决了可能维持其烟草依赖的独特心理因素。这项拟定的双盲、安慰剂对照、随机试验将评估BA加伐尼克兰治疗当前或最近（过去一年）MDD吸烟者烟草依赖的疗效。将630名具有至少中度抑郁症状的每日（e5支烟/天）吸烟者随机接受12周的四种治疗之一：1）标准行为停止治疗（ST）+安慰剂; 2）BA与ST（BA）+安慰剂; 3）ST +伐尼克兰;或4）BA +伐尼克兰。BA和ST将分8次进行，每次1小时，前四周每周一次，后8周每两周一次。随机化将根据临床研究中心（西北大学，宾夕法尼亚州）、性别和抑郁症状的严重程度（中度vs.重度）进行分层。主要结局将是戒烟后24周时经一氧化碳（CO）验证的7天时点戒烟率。其他目的包括评估伐尼克兰和安慰剂组之间的不良事件发生率，并通过快感缺乏、认知功能（注意力和记忆力）、香烟奖励值以及渴望和戒断来测试治疗效果的中介作用。这将是第一个在该人群中进行的具有充分把握度的BA戒烟试验;第一个在社区MDD吸烟者样本中评估伐尼克兰的RCT;以及第一个评估这两种治疗的主要和联合效应的RCT。

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.