Therapeutic advances in the treatment of nicotine addiction: present and future.

While the proportion of the adult population that smokes has declined steadily in several westernized societies, the rate of successful quit attempts is still low. This is because smokers develop nicotine dependence, a powerful addiction that may require multiple attempts and long-term treatment to achieve enduring abstinence. Currently available first-line agents for smoking cessation therapy include nicotine replacement therapy (available in several formulations, including transdermal patch, gum, nasal spray, inhaler, and lozenge), bupropion (an atypical antidepressant), and varenicline (a partial agonist of the α4β2 nicotinic acetylcholine receptor that was recently developed and approved specifically for smoking cessation therapy). Second-line agents are nortriptyline (a tricyclic antidepressant agent) and the antihypertensive agent clonidine. With the exception of varenicline, which has been shown to offer significant improvement in abstinence rates over bupropion, all of the available treatments appear similarly effective. The adverse event profiles of nortriptyline and clonidine make them more appropriate for second-line therapy, when first-line treatments have failed or are not tolerated. However, the currently marketed smoking cessation drugs reportedly lack high levels of efficacy, particularly in real-life settings. New medications and vaccines with significant clinical advantage are now in the advanced stage of development and offer promise. These include nicotine vaccines and monoamine type B inhibitors. In this review article we discuss current and emerging pharmacotherapies for tobacco dependence focusing on their mechanisms of action, efficacy and adverse event profiles.