Affective trajectories during adaptive pharmacotherapy for smoking cessation: Insights from EMA data

Background: Medications such as varenicline and combination nicotine replacement therapy (NRT) have demonstrated efficacy in promoting smoking cessation. However, the underlying psychological mechanisms that drive successful abstinence are less well understood. This study used Ecological Momentary Assessment (EMA) to evaluate the impact of cessation medications and adaptive treatment phases on affect among adults undergoing a two-phase smoking cessation trial. Methods: Adult smokers (N=490) were randomized to receive varenicline (VAR) or nicotine replacement therapy (NRT) in a two-phase study. At the end of 6-week Phase 1, non-abstinent participants were re-randomized for the 6-week Phase 2 to continue, switch, or augment their pharmacotherapy, while abstinent participants continued with their initial pharmacotherapy. Participants provided daily ecological momentary assessment (EMA) data on positive and negative affect, which were averaged by week and phase. Linear mixed effects models were used to examine the effects of medication group, treatment phase, and weeks since quit date on positive and negative affect, allowing the effect of phase to vary randomly by subject. Results: Several trends emerged when examining the affect trajectories over time. Visual inspection of the data suggests that participants on augmented medication tended to show greater improvements in affect scores compared to those remaining on standard NRT or varenicline alone. For positive affect, individuals in the augmented varenicline and augmented NRT groups showed an upward trajectory in Phase 2, with mean positive affect increasing steadily in the weeks following adaptation of their medication regimen. In contrast, participants in the standard NRT and varenicline groups demonstrated relatively stable or only modest increases. For negative affect, participants who were augmented in Phase 2 exhibited sharper decreases in negative affect, while those in the non-augmented medication showed more variable or persistent negative affect scores across both phases. Conclusion: Adaptive pharmacotherapy strategies for smoking cessation show greater improvement in positive affect and reduction in negative affect over time. Importantly, there was substantial heterogeneity in affective response, suggesting that individual characteristics such as age and sex may influence emotional adjustment during smoking cessation. Clinicians should consider evaluating and, when appropriate, adjusting medication regimens to support desirable affective trajectories throughout the quitting process. Future studies should investigate how changes in affect are linked to abstinence outcomes and explore how personalized medication strategies can optimize both affect and quit rates in diverse populations.