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 (χ2 = 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.