Pharmacotherapy for Smoking Cessation

Quitting smoking is one of the primary lifestyle changes that reduce the risk of cardiovascular disease in primary and secondary prevention. However, the addictive nature of nicotine makes smoking cessation difficult to initiate, and withdrawal symptoms, including cravings for cigarettes, make continued abstinence difficult to maintain. Studies show that the majority of serious quit attempts will fail within 1 year.67 This is understandable in the light of evidence showing that cigarette dependence produces long-lasting structural and functional changes in the central nervous system.67,68 Fortunately a number of drug therapies have been established as first-line therapies to aid smoking cessation. Fewer therapies have been shown to be effective in the maintenance of cessation.69

Nicotine replacement therapy (NRT) and bupropion are two pharmacotherapeutic options that are recommended as first-line treatments for motivated smokers trying to quit.67,70 The recommended duration of therapy for bupropion (Zyban) is 7 to 12 weeks; for NRTs,treatment duration ranges from 4 weeks to 6 months. NRT has been shown to be effective in the form of gum, transdermal patches, nasal spray, inhaler, lozenges, and sublingual tablets. NRT and bupro-pion can be combined. A medical model for the prescription and follow-up of bupropion has been described.71 The choice of medical therapy should be based on patient preference, history of previous use, contraindications, adverse effects, and physician experience.71

Recently, varenicline, a highly selective a4p2 nicotinic receptor partial agonist, has been developed specifically for smoking cessation. Knockout and knock-in studies in mice have shown that the a4p2 nicotinic acetylcholine receptors are necessary and sufficient for dopamine release and nicotine addiction to be established.72,73 Studies have shown an increased odds ratios for continuous abstinence from cigarettes with varenicline compared to placebo or bupropion.68

Although these therapies have demonstrated efficacy in the acute stages of quitting, the duration of treatment that is currently recommended may not be sufficient for smokers to maintain abstinence from smoking.74,67 In one trial,smokers who quit after 7 weeks of treatment with open-label bupropion were randomized to bupropion or placebo for a further 45 weeks.75 A significant benefit from continued therapy was evident at the end of the randomized phase and at 6 months thereafter, though not at 1 year. In a study published as an abstract to date, an additional 12 weeks of treatment with varenicline improved cessation rates 6 months after the end of treatment in subjects who had quit smoking with the aid of an initial 12-week course of varenicline.68 These results suggest that for some smokers, the use of long-term treatment may be beneficial.

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