Which is the best primary medication for long-term smoking cessation--nicotine replacement therapy, bupropion or varenicline?

Nicotine chewing gum has been available since 1982, when it was shown to increase smoking cessation rates by approximately 1.5- to 2-fold after 12 months. Despite the introduction of many other preparations of nicotine (sublingual, lozenge, transdermal, nasal spray and inhaler) and numerous other clinical trials, there has been no major improvement in effectiveness for smoking cessation, just an increase in the choice of how the nicotine replacement therapy (NRT) is administered. Smoking cessation rates with NRT are similar in subjects with serious chest and cardiovascular disorders. There is no evidence that intensive counselling improves the smoking cessation rates with NRT over standard counselling. The first major alternative to NRT introduced for smoking cessation was bupropion, an inhibitor of the neuronal uptake of noradrenaline and dopamine. Bupropion is effective for smoking cessation, and effectiveness is improved by a moderate level of counselling. A long-term direct comparison of bupropion with transdermal nicotine showed than bupropion was more effective than nicotine. Despite this, NRT remains the standard treatment for smoking cessation in many countries. An exciting new development for the treatment of smoking cessation is varenicline, a partial agonist at nicotinic alpha4beta2 receptors. A direct comparison of varenicline with bupropion has shown that varenicline is as least as good as and probably more effective than bupropion for smoking cessation. At present, the number of subjects who have used varenicline in clinical trial is relatively small, and probably does not allow assessment of any rare serious adverse effects. Thus, it may be premature to recommend varenicline for smoking cessation in preference to bupropion.