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

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 preloading, using mediation analysis. Design Randomised controlled trial of nicotine preloading. Potential mediators were assessed at baseline and one week into the pre-loading (three weeks prior to quitting). In addition to this, urges to smoke in abstainers were assessed one week after the target quit date. Setting England Participants 1792 smokers who wanted to quit attending specialist smoking cessation services in England were enrolled between 13/08/2012 and 10/03/2015. Intervention and comparator: Participants were randomised to either standard smoking cessation medications accompanied by behavioural support or the same treatment supplemented by nicotine ‘preloading’, i.e. four weeks of 21mg 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 four weeks post target quit date. Potential mediators included Modified Cigarette Evaluation Questionnaire with subscales assessing satisfaction, reward, craving and aversion; ratings of strength and frequency of urges to smoke; Mood and Physical Symptoms Scale assessing cigarette withdrawal symptoms; two items from Nicotine Dependence Syndrome Scale assessing smoking stereotypy; self-reported reduction in cigarettes per day and in CO reading; post-TQD medication adherence; self-efficacy; nausea. Findings Preloading reduced urges to smoke at three weeks pre-quit (p Conclusions Nicotine preloading appears to facilitate smoking abstinence by reducing urges to smoke and smoke intake before quitting and urges to smoke after quitting.