Time-Varying Mediation of Pharmacological Smoking Cessation Treatments on Smoking Lapse via Craving, Cessation Fatigue, and Negative Mood

Abstract

Introduction: The addictive nature of nicotine makes smoking cessation an extremely challenging process. With prolonged exposure, tobacco smoking transforms from being a positive reinforcer to a negative one, as smoking is used to mitigate aversive withdrawal symptoms. Studying the variations in withdrawal symptoms, especially during their peak in the first week of a quit attempt, could help improve cessation treatment for the future. The time-varying mediation model effectively studies whether altering withdrawal symptoms act as mediators in the pathway between treatment and cessation.

Aims and methods: This secondary data analysis of a randomized clinical smoking cessation trial of three pharmacotherapy regimens (nicotine patch, varenicline, and nicotine patch + mini-lozenge) analyzes ecological momentary assessment (EMA) data from the first 4 weeks post-target quit day (TQD). We assess whether withdrawal symptoms (eg, negative mood, cessation fatigue, and craving) mediate the pathway between pharmacotherapy and daily smoking status and whether this effect varies over time.

Results: We found a statistically significant time-varying mediation effect of varenicline on smoking status through craving, which shows decreasing risk of lapse via reduction in craving. We did not find significant time-varying mediation effects through negative mood and cessation fatigue.

Conclusions: This study supports the importance of craving suppression in the smoking cessation process. It also helped identify specific timepoints when withdrawal symptoms increased that would likely benefit from targeted cessation intervention strategies.

Implications: This study aimed to understand the underlying dynamic mechanisms of the smoking cessation process using a new analytical approach that capitalizes on the intensive longitudinal data collected via EMAs. The findings from this study further elucidate the smoking cessation process and provide insight into behavioral intervention targets and the timing of such interventions through the estimation of time-varying mediation effects.

Figure 1.

Mediation effect of craving and α- and β-path effects with 95% CI estimated for the binary outcome (smoking status—Yes/No). The left column of the figure shows results of mediation analysis for varenicline vs. nicotine patch and the right column shows results of mediation analysis for cNRT vs. nicotine patch. The top panels show the time-varying mediation effect estimates at each timepoint of interest. The y-axis is on the odds scale. The middle panel shows the time-varying effect of varenicline/cNRT on craving compared with the patch. The y-axis is on the linear scale. The bottom panel shows the effect of craving on smoking status when the treatment is held constant. The y-axis is on the odds scale. CI = confidence interval, cNRT = combination nicotine replacement therapy.