BACKGROUND AND AIMS: Bupropion was introduced for smoking cessation following a 
pivotal trial showing that it gave improved efficacy over the nicotine patch and 
also suggesting combination treatment was beneficial. We tested in clinical 
practice for an effectiveness difference between bupropion and nicotine 
replacement therapy (NRT), whether the combination improves effectiveness and 
whether either treatment might be more beneficial for certain subgroups of 
smokers.
DESIGN: Open-label randomized controlled trial with 6-month follow-up.
SETTING: Four UK National Health Service (NHS) smoking cessation clinics.
PARTICIPANTS: Smokers (n = 1071) received seven weekly behavioural support 
sessions and were randomized to an NRT product of their choice (n = 418), 
bupropion (n = 409) or NRT plus bupropion (n = 244).
MEASURES: The primary outcome was self-reported cessation over 6 months, with 
biochemical verification at 1 and 6 months. Also measured were baseline 
demographics, health history, smoking characteristics and unwanted events during 
treatment.
FINDINGS: Abstinence rates for bupropion (27.9%) and NRT (24.2%) were not 
significantly different (odds ratio = 1.21, 95% confidence interval = 
0.883-1.67), and the combination rate (24.2%) was similar to that for either 
treatment alone. There was some evidence that the relative effectiveness of 
bupropion and NRT differed according to depression (χ(2) = 2.86, P = 0.091), 
with bupropion appearing more beneficial than NRT in those with a history of 
depression (29.8 versus 18.5%). Several unwanted symptoms were more common with 
bupropion.
CONCLUSION: There is no difference in smoking cessation effectiveness among 
bupropion, nicotine replacement therapy and their combination when used with 
behavioural support in clinical practice. There is some evidence that bupropion 
is more beneficial than nicotine replacement therapy for smokers with a history 
of depression.