The rate of smoking is 2–3 times higher among adults experiencing past year mental health disorders than among the general population in the United States (40–60% vs. 19%; Weinberger et al., 2020). Major depressive disorder (MDD) is one of the most common mental health disorders, with a point prevalence among adults aged ≥ 20 years old of 8.1% (Brody et al., 2018). The higher rate of smoking in this population translates into higher rates of cancer and cardiovascular disease and lower overall life expectancy, vs. the general population (Druss & Walker, 2011).

Studies conducted over the last 10 years have found that FDA-approved medications for smoking and guideline-based behavioral interventions are safe and effective for smokers with MDD (Anthenelli et al., 2016, Hawes et al., 2021). However, compared to no treatment or placebo, smokers with MDD still show lower quit rates than the general population, even when receiving the same treatments (Anthenelli et al., 2016).

In the general population, one of the strongest predictors of response to smoking cessation treatments is treatment adherence (Fiore et al., 2008, Pacek et al., 2018). Upwards of one-quarter to one-half of smokers enrolled in clinical trials involving FDA-approved medications or behavioral interventions are non-adherent, and quit rates are nearly two times lower for these smokers vs. those who are adherent (Okuyemi et al., 2010, Grenard et al., 2011, Peng et al., 2018, Crawford et al., 2019). Regarding predictors of adherence, one review indicated that increased medication adherence is associated with demographic characteristics (e.g., male, non-Hispanic Whites, greater education), less psychiatric comorbidity, lower degree of nicotine dependence, and a lack of adverse treatment-related side effects (Pacek et al., 2018). Other studies have found medication adherence to be associated with nicotine withdrawal symptoms (Catz et al., 2011), engagement in complementary (e.g., socializing with friends) or substitute (e.g., exercise) reinforcers (Handschin et al., 2018), and reductions in the rewarding experience from smoking (Crawford et al., 2019). To date, there is a paucity of data on the rates of adherence to tobacco treatments, how variability in adherence is associated with cessation outcomes, and what factors are associated with adherence among smokers with MDD.

Given these notable gaps in the current literature, we used data from a double-blind placebo-controlled clinical trial evaluating varenicline and behavioral activation counseling for tobacco use among smokers with MDD to examine the rate of medication and counseling adherence in this population, the association between medication and counseling adherence and end-of-treatment smoking cessation (12 weeks), and baseline and early phase (i.e., across the first two weeks of treatment) changes in variables potentially associated with medication and counseling adherence. The results of this study may contribute to our understanding of why smokers with MDD show low rates of cessation following treatment and identify potential targets for intervening to promote greater adherence in this under-served community of smokers.