Effects Of The Nicotinic Partial Agonist Varenicline On Smoking Lapse Behaviour In Schizophrenia

Background: Varenicline, a nicotinic receptor partial agonist, is a first-line smoking cessation pharmacotherapy that may reduce smoking relapse in smokers with schizophrenia (SWS). The use of human laboratory models may allow the determination of potential mechanisms to improve treatment outcomes. The first instance of smoking during a quit attempt (a "smoking lapse") is one of the best predictors of relapse. The aim of this study was to investigate effects of varenicline on smoking lapse in SWS and controls using a validated model of smoking lapse behaviours.Methods: Varenicline was titrated up to 2mg/d over 4 days and continued for a total of 6 days using a randomized, double-blind, placebo-controlled cross-over human laboratory lapse study design in SWS (n=14) and nonpsychiatric control (n=14) smokers.Results: Varenicline nonsignificantly increased time to lapse in both SWS and control groups. However, these effects were most pronounced in SWS compared to controls with higher levels of nicotine dependence (Fagerstrom Test for Nicotine Dependence score =6; Cohen's d=0.47 SWS; d=0.24 controls). There were no medication effects related to cognitive function, withdrawal, craving, or smoking topography outcomes.Conclusions: Our preliminary findings lack evidence in supporting the potential efficacy of varenicline on smoking relapse, particularly in SWS that may in part relate to our small sample size. Larger studies to further delineate the specific mechanisms by which varenicline ameliorates smoking relapse in SWS are needed, possibly in combination with adjunctive treatments to enhance overall relapse-prevention outcomes.