Both nortriptyline and bupropion have been associated with improvements in smoking cessation rates, and both drugs have been cited as effective in a Cochrane review and by the GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines.

Placebo-controlled trials have documented the effectiveness of bupropion and nortriptyline for smoking cessation. The one trial in which the effectiveness of these drugs was compared directly suggested that bupropion and nortriptyline are equally effective. However, a larger proportion of patients who were being treated with buproprion withdrew from the study than was the case in the nortriptyline group. Subgroup analysis suggested that buproprion may be more effective than nortriptyline in patients with major depressive disease but that the drugs are equally effective in patients with no history of major depressive disease.

According to these data, in patients with advanced COPD who do not have major depressive disease, appropriate smoking cessation therapy should be selected primarily on the basis of adverse effects. In the study directly comparing the effectiveness of buproprion and nortriptyline for smoking cessation, nuisance side effects such as dry mouth and constipation occurred more commonly in nortriptyline-treated patients, but the incidence of withdrawal from the study because of adverse effects was higher in the buproprion group. Furthermore, Health Canada has issued an advisory regarding severe reactions associated with bupropion.
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For patients with COPD, smoking cessation is the only intervention that attenuates the abrupt progressive decline in pulmonary function. Patients with more advanced pulmonary disease may also experience weight loss because of the increased oxygen demands associated with the disease. Weight loss has been identified as a prognostic factor for death, and therefore weight gain is desirable and improves survival in this population. In view of comparable efficacy and a lower incidence of adverse effects necessitating drug discontinuation, nortriptyline appears to offer advantages over buproprion for smoking cessation in patients with COPD.