Mediators of the effect of nicotine pre-treatment on quitting smoking

© 2018 Society for the Study of Addiction Background and aims: Using smoking cessation medications for several weeks prior to quitting smoking facilitates quitting success, but how it does so is not clear. Candidate theories are that pre-cessation medication enhances self-efficacy, facilitates medication adherence post-quit, induces aversion to smoking, reduces reward from smoking or reduces the drive to smoke. We investigated these pathways using data from a large trial of nicotine pre-loading, using mediation analysis. Design: Randomized controlled trial of nicotine pre-loading. Potential mediators were assessed at baseline and 1 week into the pre-loading (3 weeks prior to quitting). In addition to this, urges to smoke in abstainers were assessed 1 week after the target quit date. Setting: England. Participants: A total of 1792 smokers who wanted to quit attending specialist smoking cessation services in England were enrolled between 13 August 2012 and 10 March 2015. Intervention and comparator: Participants were randomized to either standard smoking cessation medications accompanied by behavioural support or the same treatment supplemented by nicotine ‘pre-loading’, i.e. 4 weeks of 21 mg nicotine patch use prior to quitting. Measurements: The primary outcome, selected for its proximity in time to potential mediators, was biochemically validated abstinence from smoking at 4 weeks post-target quit date. Potential mediators included the Modified Cigarette Evaluation Questionnaire, with subscales assessing satisfaction, reward, craving and aversion; ratings of strength and frequency of urges to smoke; the Mood and Physical Symptoms Scale assessing cigarette withdrawal symptoms; two items from the Nicotine Dependence Syndrome Scale assessing smoking stereotypy; self-reported reduction in cigarettes per day and in carbon monoxide (CO) reading; post-target quit day (TQD) medication adherence; self-efficacy; nausea. Findings: Pre-loading reduced urges to smoke at 3 weeks pre-quit (P < 0.001) and exhaled CO concentrations (P < 0.001), and also urges to smoke post-quit in abstainers (P = 0.001). At 3 weeks pre-quit, it also reduced cigarette consumption, enjoyment of and satisfaction from smoking and smoking reward and increased nausea, aversion (all P < 0.001) and smoking stereotypy (P = 0.003). Only the first three variables, however (reduced smoke intake and reduced urges to smoke pre- and post-quit), mediated abstinence from smoking at 4 weeks and only the latter two mediated abstinence at 6 months (indirect mediating effects P < 0.05). Conclusions: Nicotine pre-loading appears to facilitate smoking abstinence by reducing urges to smoke and smoke intake before quitting and urges to smoke after quitting.