Evaluating Treatment Mechanisms of Varenicline: Mediation by Affect and Craving

Abstract

Introduction Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid cessation by attenuating these changes; however, this mediational pathway has not been formally evaluated in placebo-controlled trials. Thus, trajectories of negative affect (NA), positive affect (PA), and craving were tested as mediators of the effect of varenicline on smoking cessation. Methods Secondary data analysis was conducted on 828 adults assigned to either varenicline or placebo in a randomized controlled trial for smoking cessation (NCT01314001). Self-reported NA, PA, and craving were assessed 1 week pre-quit, on the target quit day (TQD), and 1 and 4 weeks post-TQD. Results Across time, NA peaked 1 week post-quit, PA did not change, and craving declined. Less steep rises in NA (indirect effect 95% CI: 0.01 to 0.30) and lower mean craving at 1 week post-quit (CI: 0.06 to 0.50) were mediators of the relationship between varenicline and higher cessation rates at the end of treatment. PA was associated with cessation, but was not a significant mediator. Conclusions These results partially support the hypothesis that varenicline improves smoking cessation rates by attenuating changes in specific psychological processes and supported negative affect and craving as plausible treatment mechanisms of varenicline. Implications The present research provides the first evidence from a placebo-controlled randomized clinical trial that varenicline’s efficacy is due, in part, to post-quit attenuation of NA and craving. Reducing NA across the quit attempt and craving early into the attempt may be important treatment mechanisms for effective interventions. Further, post-quit NA, PA, and craving were all associated with relapse and represent treatment targets for future intervention development.

Effect of Extending the Duration of Prequit Treatment With Varenicline on Smoking Abstinence

“…33 Craving and withdrawal (unregistered but commonly reported outcomes in varenicline trials 1,20,21,48,49 ) were moderated by sex in a manner consistent with the hypothesized greater benefit for women. It is possible that extended run-in varenicline treatment potentiates, at least among women, the mechanisms of action recently reported 50 for standard varenicline (reduced craving and negative affect). However, in the present study, this did not translate into a significant enhancement of smoking abstinence.…”