Impact of Early Nausea on Varenicline Adherence and Smoking Cessation.

Varenicline effectiveness may be related to the level of adherence, which might be reduced by adverse effects such as nausea. The aim of the study was to test a possible effect of nausea on smoking cessation outcomes mediated by adherence.Mediation path analysis SETTING: Multiple sites within Canada and the United States.Treatment-seeking smokers receiving varenicline from two smoking cessation clinical trials: Quit2Live (NCT01836276; n=449) and Pharmacogenetics of Nicotine Addiction Treatment (PNAT) (NCT01314001; n=421).Nausea severity was collected through self-report and adherence was biologically assessed using varenicline concentrations (Quit2Live, plasma sample at Week 4; PNAT, saliva sample at Week 2). In Quit2Live, the endpoints were cotinine-verified abstinence at Weeks 4, 12, and 26. In PNAT, the endpoints were carbon monoxide-verified abstinence at Weeks 2, 12, and 26.Early nausea was indirectly associated with lower cessation rates at multiple timepoints (ORs ranging from 0.92-0.94; 95%CI between 0.83-0.99) in a relationship mediated by reduced varenicline adherence (assessed by plasma varenicline concentrations) in the Quit2Live trial. This relationship between nausea, adherence and cessation was similar in direction but weaker in effect size (ORs ranging from 0.98-0.99; 95%CI between 0.90-1.03) in the PNAT trial, where adherence was assessed using salivary varenicline concentrations.Early nausea during varenicline treatment may be indirectly associated with lower likelihood of smoking cessation through reducing varenicline adherence.