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Nortriptyline is a tricyclic antidepressant that has been shown in several double-blind, placebo-controlled trials to be superior to placebo (Hall et al. 1998; Prochazka et al. 1998) and to have comparable efficacy to bupropion (Hall et al. 2002). Its efficacy may be improved with higher- rather than lower-intensity behavioral therapies. Its mechanism of action is thought to relate to norepinephrine and serotonin reuptake blockade. Side effects include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with past histories of major depression, but its potential for fatal overdose has likely limited its utilization. Nonetheless, it can be recommended as a second-line agent after nicotine replacement therapies and bupropion, though more study of this agent is necessary.

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