Varenicline as a First-Line Treatment for Individuals With Current Major Depressive Disorder Who Smoke Cigarettes

Abstract

In this issue, Kypriotakis and colleagues (1) present novel data from the EAGLES trial (Evaluating Adverse Events in a Global Smoking Cessation Study) demonstrating the safety of varenicline, bupropion, and nicotine replacement therapy (NRT) for cessation of cigarette smoking for people with a current or past diagnosis of major depressive disorder (MDD). Because the authors examined current and past MDD separately, they were able to demonstrate that all three pharmacological treatments improved cessation outcomes compared to placebo for people with past MDD. Only var-enicline, however, demonstrated improved cessation outcomes compared to placebo for people with current MDD. Similarly, in Cinciripini and colleagues' (2) analysis of the EAGLES data, 31.2% of people with depression (a combined group with past and/or current MDD) reported continuous abstinence using varenicline, representing the best outcome of the four conditions (compared with 23.0% receiving bupropion, 22.6% receiving NRT, and 13.4% receiving a placebo). These findings have important clinical implications for determining first-line tobacco treatments for people with current MDD. These data add to the evidence that pharmacological treatments for tobacco cessation are safe for people with depression and that mental health symptoms not only do not worsen but improve with tobacco cessation (3-5). We are unaware of any pharmacological properties of varenicline that would suggest that it has a direct effect on depressive symptoms. It is reasonable to assume that varenicline's superior effect on quitting is associated with decreased depressive symptoms. One study, however, found that depressive symptoms decreased for participants with schizophrenia spectrum disorders who received varenicline treatment and behav-ioral interventions for cigarette smoking cessation regardless of their cessation status (i.e., quit smoking vs. continued smoking) (6), thus indicating that it is not simply quitting cigarette smoking that accounts for the decreased depression. It remains possible, however, that the behavioral intervention , rather than the varenicline itself, contributed to the effect on depression. The Kypriotakis et al. study and other EAGLES trial data (7) demonstrate the safety of varenicline for individuals with psychiatric comorbidity, and the U.S. Food and Drug Administration removed the black box warning for varenicline related to suicidal thoughts and behaviors in 2015 (8)