The findings of this prospective study suggest that sustained-release bupropion therapy is effective in delaying relapse to smoking independent of a past history of major depressive disorder. This is the first study to examine bupropion use for smoking relapse prevention in association with major depression. Our results indicate no significant difference between MDD history groups in median time to smoking relapse or the overall percent of subjects who relapsed. Thus, when used for longer-term treatment, bupropion appears equally effective across the range of smokers with and without past major depression comorbidity. This contrasts with other research findings of an association between a history of MDD and higher rates of smoking relapse following use of clonidine.1
However, that study was an efficacy trial utilizing the pharmacotherapy for only a few weeks. While there was little change in percent abstinent from smoking between weeks 52 and 104 for placebo subjects, we found there was a sizable decrease for those who had received active medication. A history of MDD did not affect this outcome. However, this does suggest that while bupropion is helpful, it may need to be maintained on a chronic basis.
Our results should be interpreted cautiously, due to the small sample size in the MDD group that limits the statistical power to detect differences in treatment outcomes. Given the sample size of 80 for those with a history of MDD randomly assigned to the double-blind phase and the week 52 abstinence rates, this study provided statistical power of 27%, 54%, 73%, and 84% to detect a medication assignment-by-MDD history group interaction with a 2-, 3-, 4-, and 5-fold increase in treatment efficacy, respectively, for those with versus without a history of MDD (i.e., x% power to detect an odds ratio for the interaction effect). Among subjects with a history of MDD, 52% of those receiving bupropion were abstinent at 1 year compared to only 36% of those using placebo. Although not statistically significant, this difference is of meaningful clinical interest, and underscores the need for replication of our results in a larger sample of smokers with a past history of major depressive disorder.
The finding of a lack of effect of MDD history on treatment outcomes should also be interpreted in light of the potential for selective attrition prior to randomization to the double-blind phase. At the end of the open-label phase, nonresponders differed from bupropion responders on several baseline characteristics, including gender and severity of nicotine dependence. It is therefore possible that a history of major depressive disorder may have affected outcome or interacted with medication assignment if the study design did not require exclusion of bupropion nonresponders.
Some subject characteristics limit generalizability of the findings. They were primarily white, well-educated, and motivated to stop smoking. The stringent screening criteria for this trial (e.g., psychiatric disorder) also limit the representativeness of the smokers with MDD history to other smokers in the population with a history of MDD. However, these study criteria were very similar to other trials of pharmacotherapy for smoking cessation.1,5,21
A population-based study indicates that about 40% of current smokers report a current or past psychiatric disorder.2
Nonetheless, we found that only 5% of those screened by telephone (based on data obtained at the Mayo site) were excluded based on a psychiatric disorder. Moreover, given the selection criteria, the dispersion of baseline BDI scores were restricted to the lower end, which likely limited our ability to detect an association between changes in depressive symptoms and MDD history and/or medication assignment. The effectiveness of bupropion for smoking abstinence and relapse prevention among patients presenting with current depression is a clinical issue that warrants empirical attention.