Johnstone Samantha, Cooper Robert K, Wray Jennifer M, Tonkin Sarah S, Knapp Kyler S, Colder Craig R, Maguin Eugene, Mahoney Martin C, Tiffany Stephen T, Brandon Thomas H, Ashare Rebecca L, Tyndale Rachel F, Hawk Larry W
Department of Psychology, University at Buffalo, Buffalo, NY, USA.
Ralph H Johnson Veteran's Affairs Healthcare System, Charleston, SC, USA.
Addiction. 2025 Jun;120(6):1223-1237. doi: 10.1111/add.16772. Epub 2025 Feb 6.
Mechanisms of varenicline preloading in promoting smoking abstinence have not been evaluated. Based on an extinction of reinforcement framework, we tested the hypothesis that pre-quit reductions in smoking rate mediate the effect of extended preloading on abstinence. We also tested alternative indicators of change in smoking reinforcement, as well as smoking aversion, nausea and abstinence self-efficacy as candidate mediators.
DESIGN, PARTICIPANTS AND INTERVENTION: Randomized, double-blind, placebo-controlled trial (NCT03262662) comparing extended (4-week varenicline) to standard (3 weeks of placebo, 1-week varenicline) preloading, preceding 11 weeks of open-label varenicline, in 320 adults (56% female). The primary outcome was self-reported continuous smoking abstinence during the last 4 weeks of treatment, with cotinine bio-verification at end of treatment (EOT).
University at Buffalo, State University of New York, USA (part of the trial was conducted at participants' homes due to the COVID-19 pandemic).
Candidate mediators, including smoking rate and subjective effects of smoking (reward, satisfaction, aversion), self-reported craving, withdrawal, nausea and abstinence self-efficacy, were assessed daily during the pre-quit period with ecological momentary assessment. At two laboratory visits participants completed a choice task to assess smoking reinforcement.
There was a statistically significant indirect effect of extended preloading on greater EOT abstinence rates through pre-quit declines in smoking rate [ab = 0.284, 95% confidence interval (0.072,0.616)] and percent reduction in smoking across the pre-quit period [ab = 0.225, (0.080,0.437)]. There were also statistically significant indirect effects through reductions in pre-quit craving [ab = 0.150, (0.01,0.420)] and increases in pre-quit self-efficacy [ab = 0.157, (0.038,0.375)]. Sex-specific analyses suggested these mediated effects were consistently limited to females. No other candidate mediators yielded statistically significant indirect effects.
Extended varenicline preloading mediated smoking abstinence through reduced pre-quit smoking and craving among female smokers seeking to quit; increased pre-quit abstinence self-efficacy was also a significant mediator.
伐尼克兰预加载促进戒烟的机制尚未得到评估。基于强化消退框架，我们检验了以下假设：戒烟前吸烟率的降低介导了延长预加载对戒烟的影响。我们还检验了吸烟强化变化的替代指标，以及吸烟厌恶、恶心和戒烟自我效能作为候选中介因素。
设计、参与者与干预：随机、双盲、安慰剂对照试验（NCT03262662），比较延长（4周伐尼克兰）与标准（3周安慰剂、1周伐尼克兰）预加载，随后进行11周开放标签伐尼克兰治疗，共320名成年人（56%为女性）。主要结局是治疗最后4周自我报告的持续戒烟情况，治疗结束时（EOT）进行可替宁生物验证。
美国纽约州立大学布法罗分校（由于新冠疫情，部分试验在参与者家中进行）。
在戒烟前阶段，通过生态瞬时评估每日评估候选中介因素，包括吸烟率和吸烟的主观效应（奖励、满意度、厌恶）、自我报告的渴望、戒断症状、恶心和戒烟自我效能。在两次实验室访视中，参与者完成一项选择任务以评估吸烟强化。
通过戒烟前吸烟率的下降，延长预加载对更高的治疗结束时戒烟率有统计学显著的间接效应[ab = 0.284，95%置信区间（0.072，0.616）]，以及整个戒烟前阶段吸烟量减少的百分比[ab = 0.225，（0.080，0.437）]。通过戒烟前渴望的减少[ab = 0.150，（0.01，0.420）]和戒烟前自我效能的增加[ab = 0.157，（0.038，0.375）]也有统计学显著的间接效应。性别特异性分析表明，这些中介效应始终仅限于女性。没有其他候选中介因素产生统计学显著的间接效应。
延长伐尼克兰预加载通过减少寻求戒烟的女性吸烟者戒烟前的吸烟量和渴望来介导戒烟；戒烟前戒烟自我效能的增加也是一个重要的中介因素。
