Development of depression during placebo-controlled trials of bupropion for smoking cessation: Case reports

Background: Recent attention has focused on the relationship between depres sion and smoking cessation. This article describes 5 cases of severe depres sion that occurred during 2 multicenter trials using bupropion for smoking cessation. Method: Subjects were participants in 2 randomized, double-blind, placebo-c ontrolled studies investigating the efficacy of bupropion fbr smoking cessa tion. Data from both trials were restricted to subjects at the Rochester, M inn., site in order to have access to the medical records for information o n depression diagnosis, treatment, and follow-up. The first trial involved 205 smokers who received active bupropion or placebo for 7 weeks. In the se cond trial, 252 smokers received open-label bupropion therapy for 7 weeks. Those abstinent from smoking at the end of week 7 (N = 148) were randomly a ssigned to a 45-week, double-blind, relapse-prevention phase. Results: In the first trial, 1 of the 205 participants (0.49%) experienced major depression during the 7-week treatment phase. In the second trial, no ne of the 252 subjects developed major depression during the 7-week, open-l abel phase. When results of both trials across the 7-week treatment phase ( study 1, N = 205; study 2, N = 252) are combined, the rate of developing ma jor depression was 0.22% (1 of 457). Of the 457 subjects, none of the 51 wh o received placebo and 1 (0.25%) of the 406 who received active bupropion d eveloped major depression. In the second trial, 4 (2.7%) of the 148 subject s randomly assigned to the 45-week, relapse-prevention phase developed depr ession. Overall, 4 of the 5 cases from the 2 trials had a past history of m ajor depression prior to study entry, beet none had current major depressio n. Conclusion: Major depression may occur in some individuals during smoking c essation treatment with bupropion.