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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 .
METHODS	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 .
METHODS	Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52 .
METHODS	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 ) .
RESULTS	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 ) .
RESULTS	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 ) .
RESULTS	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 .
CONCLUSIONS	Neither outcome was significantly different at 52 weeks .
CONCLUSIONS	Further research is required to determine the role of combination therapy in smoking cessation .
BACKGROUND	clinicaltrials.gov Identifier : http://clinicaltrials.gov/show/NCT00935818 .

