AbstractSmoking remains a major public health challenge. Nicotine is the main psychoactive drug responsible for the addictive nature of tobacco, explaining why many smokers fail to quit without assistance. Pharmacotherapy for smoking cessation is deemed effective for a broad range of populations and should be routinely offered to smokers interested in making a quit attempt. Varenicline, a partial agonist at the α4β2 nicotinic receptor increases chances of quitting three-fold compared to placebo in smokers without comorbidities, and in smokers with cardiovascular disease or chronic obstructive pulmonary disease. Persons with mental illness have high rates of smoking, and the potential impact of varenicline on mental status and the underlying pathophysiology of mental illness, has become a salient concern. Varenicline is an appropriate aid for smoking cessation in patients with medical and/or psychiatric comorbidity. This conclusion is supported by current evidence on the safety and tolerability of the drug.

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