Varenicline and Bupropion for Smoking Cessation

Cigarette smoking is the single most important preventable cause of morbidity, mortality and
excess health care costs in the United States and accounts for 30% of U.S. cancer deaths.
Varenicline and bupropion SR (sustained-release) are non nicotine pharmacotherapies
FDA-indicated for the treatment of tobacco dependence in cigarette smokers. Although
varenicline has proven greater efficacy than bupropion SR, both medications are associated
with high end-of-treatment smoking abstinence rates. However, almost two-thirds of smokers
treated with varenicline report smoking at 6 months. Because varenicline and bupropion SR
have different mechanisms of action and different neuropharmacologic targets, combination
pharmacotherapy with these agents may increase long-term smoking abstinence rates above what
is observed with single-agent therapy. In our recent pilot study of combination therapy
with varenicline and bupropion SR, we observed treatment to be well-tolerated with 7-day
point prevalence smoking abstinence rates of 71% (95% CI: 54-85%) at 3 months and 58% (95%
CI: 41-74%) at 6 months. Determining the efficacy of combination therapy compared to
single-agent therapy has immediate and important clinical implications. In this study, we
will conduct a randomized, multicenter, controlled clinical trial evaluating the efficacy of
combination therapy with varenicline and bupropion SR compared to varenicline and placebo in
450 cigarette smokers at the Mayo Clinic in Rochester, MN, and the University of Minnesota
in Minneapolis, MN.