The tricyclic antidepressant nortriptyline has been shown to have similar efficacy to bupropion, and this efficacy is not restricted to people with a history of depression or depressive symptoms. The adverse events reported included the well-known tricyclic effects of dry mouth, drowsiness, light-headedness and constipation. Based on experiences when used to treat depression, nortriptyline would be expected to have the potential for more serious adverse events; however, when used at 75 to 150 mg doses in smokers, dropout rates in the two trials reporting this outcome were 4% and 9%. This is similar to that for bupropion and nicotine replacement therapy. Nortriptyline is not approved for smoking cessation in Australia.

Precautions: No serious adverse events in people treated with nortriptyline were reported in the smoking cessation trials, nevertheless, it is important to consider all precautions and contraindications to tricyclic antidepressants before initiating therapy. Guidelines recommend careful monitoring of all people with underlying psychiatric illness who are quitting smoking because of the possible effects of smoking cessation (with or without drug therapy) on their illness and medication. There is the potential for significant toxicity with nortriptyline overdose. There is also a potential for pharmacokinetic and pharmacodynamic drug interactions (including serotonin toxicity) if nortriptyline is used in combination with other serotonergic agents.

At end of treatment the dose should be tapered, and the patient monitored for withdrawal symptoms. Risk factors for withdrawal symptoms may include higher doses and long treatment courses.