title: Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial.
abstract: OBJECTIVE
  Combining pharmacotherapies for tobacco-dependence treatment may increase smoking abstinence.
  
  
  OBJECTIVE
  To determine efficacy and safety of varenicline and bupropion sustained-release (SR; combination therapy) compared with varenicline (monotherapy) in cigarette smokers.
  
  
  METHODS
  Randomized, blinded, placebo-controlled multicenter clinical trial with a 12-week treatment period and follow-up through week 52 conducted between October 2009 and April 2013 at 3 midwestern clinical research sites. Five hundred six adult (≥18 years) cigarette smokers were randomly assigned and 315 (62%) completed the study.
  
  
  METHODS
  Twelve weeks of varenicline and bupropion SR or varenicline and placebo.
  
  
  METHODS
  Primary outcome was abstinence rates at week 12, defined as prolonged (no smoking from 2 weeks after the target quit date) abstinence and 7-day point-prevalence (no smoking past 7 days) abstinence. Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52. Outcomes were biochemically confirmed.
  
  
  RESULTS
  At 12 weeks, 53.0% of the combination therapy group achieved prolonged smoking abstinence and 56.2% achieved 7-day point-prevalence smoking abstinence compared with 43.2% and 48.6% in varenicline monotherapy (odds ratio [OR], 1.49; 95% CI, 1.05-2.12; P = .03 and OR, 1.36; 95% CI, 0.95-1.93; P = .09, respectively). At 26 weeks, 36.6% of the combination therapy group achieved prolonged and 38.2% achieved 7-day point-prevalence smoking abstinence compared with 27.6% and 31.9% in varenicline monotherapy (OR, 1.52; 95% CI, 1.04-2.22; P = .03 and OR, 1.32; 95% CI, 0.91-1.91; P = .14, respectively). At 52 weeks, 30.9% of the combination therapy group achieved prolonged and 36.6% achieved 7-day point-prevalence smoking abstinence compared with 24.5% and 29.2% in varenicline monotherapy (OR, 1.39; 95% CI, 0.93-2.07; P = .11 and OR, 1.40; 95% CI, 0.96-2.05; P = .08, respectively). Participants receiving combination therapy reported more anxiety (7.2% vs 3.1%; P = .04) and depressive symptoms (3.6% vs 0.8%; P = .03).
  
  
  CONCLUSIONS
  Among cigarette smokers, combined use of varenicline and bupropion, compared with varenicline alone, increased prolonged abstinence but not 7-day point prevalence at 12 and 26 weeks. Neither outcome was significantly different at 52 weeks. Further research is required to determine the role of combination therapy in smoking cessation.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: http://clinicaltrials.gov/show/NCT00935818.
authors.affiliation: Nicotine Dependence Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Ebbert
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
authors.affiliation: Nicotine Dependence Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ivana T
authors.initials: IT
authors.lastname: Croghan
authors.affiliation: Nicotine Dependence Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Schroeder
authors.affiliation: Family Medicine and Community Health, University of Minnesota, Minneapolis.
authors.forename: Sharon S
authors.initials: SS
authors.lastname: Allen
authors.affiliation: Nicotine Dependence Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: J Taylor
authors.initials: JT
authors.lastname: Hays
authors.affiliation: Nicotine Dependence Center, Mayo Clinic, Rochester, Minnesota.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Hurt
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000008:administration & dosage*; D016642:Bupropion / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011810:Quinoxalines / Q000008:administration & dosage*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D016896:Treatment Outcome; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D003692:Delayed-Action Preparations; D018765:Dopamine Uptake Inhibitors; D018722:Nicotinic Agonists; D011810:Quinoxalines; D016642:Bupropion; D000068580:Varenicline