DOI: 10.25934/pr00006050
title: Safety and efficacy of smoking cessation treatments in smokers with and without depression

description: A significant shared familial risk of depression and smoking has been identified for heavy and nicotine-dependent smokers (Johnson, Rhee, Chase, & Breslau, 2004) and a history of major depression (American Psychiatric Association, 2013) has been associated with an increased prevalence of smoking, (Breslau et al., 1991; Breslau, Kilbey, & Andreski, 1993; Kendler et al., 1993) nicotine dependence, (Breslau et al., 1991) and greater nicotine withdrawal severity. Despite the need for treatment, smokers with co-morbid psychiatric disorders have been routinely excluded from smoking cessation clinical trials. Moreover, case reports and post-marketing data have raised concerns about the safety of treating these smokers with the most effective medication available, varenicline, (Moore, Furberg, Glenmullen, Maltsberger, & Singh, 2011) despite evidence that varenicline may offer significant alleviation of withdrawal symptoms. (Rollema et al., 2007; Rollema et al., 2009) Examining the efficacy and tolerability of varenicline and other smoking cessation pharmacological treatments (within a well-designed randomized clinical trial) in smokers with depression versus those without will allow researchers and clinicians to place those surveillance and post-marketing reports in the appropriate context and offer empirically-supported guidance for the treatment of smokers with co-morbid psychiatric disorders.   Moreover, there is a compelling need to better understand the treatment of patients with depressive disorders for smoking cessation. This research has the potential to affect approximately 12 million of US adults over 18 diagnosed with depression who smoke cigarettes. Major Depressive Disorder (MDD) and symptom severity are associated with increased risk for continued smoking, heavier smoking, persistent nicotine dependence, relapse across time, as well as more frequent and sustained periods of withdrawal compared to those with no disorder. Improving treatment outcome for this vulnerable group of smokers can have significant health implications. The adverse health consequences of a poor smoking cessation treatment response among those with depressive disorders includes both an increase in morbidity and mortality from tobacco related illness as well as  dying from these disorders an average of 8.4 years earlier than those without mental health disorders. The present study is a secondary data analysis of the largest smoking cessation randomized clinical trial conducted to date involving smokers both with and without psychiatric disorders. Clinicians would benefit from additional information on which smoking cessation medication may be most efficacious in smokers with MDD.  Importantly, findings on the comparative safety of front-line smoking cessation pharmacotherapies may increase willingness of clinicians to prescribe these medications to smokers with MDD, which may be especially critical to the success of their cessation attempts. We will performe secondary analyses of safety and efficacy outcomes by MDD diagnosis in EAGLES, a 12-week, randomized, double-blind, triple-dummy, placebo- and active-(NRT)-controlled trial of varenicline and bupropion with 12-week follow-up. Primary outcomes are incidence of moderate and severe neuropsychiatric adverse events (NPSAEs) and week 9-12 continuous abstinence rates.