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ABSTRACT & COMMENTARY
Cigarette smoking remains the most important preventable cause of premature death and disability worldwide, and new ways to help smokers quit are welcome. This study was a randomized, double-blind, placebo-controlled, dose-response trial performed at three sites. The 615 subjects were randomized to placebo or 100, 150, or 300 mg daily of sustained-release bupropion for seven weeks. The target quitting date was one week after the beginning of treatment. The behavioral therapy that accompanied the pharmacologic intervention was of low intensity, similar to that which might be provided in a physician’s office. At the end of seven weeks of therapy, the rate of smoking cessation was 44.2% in the group receiving a daily dose of 300 mg and 19.0% in the placebo group. At the end of one year, the cessation rates were 23.1% and 12.4%, respectively. Bupropion was well tolerated, with the most common side effects being dry mouth, insomnia, headache, and rhinitis. Bupropion is contraindicated in those with a seizure disorder or a history of seizures.
Many of the deleterious consequences of smoking accrue with time and are not seen until mid-life, but some, like fetal exposures and infertility, affect women in the prime of reproductive life. Thus, it is imperative that physicians caring for women be familiar with therapies for smoking cessation. The mainstay heretofore has been nicotine-containing products, such as gum, nasal sprays, and patches. Although these products carry a small risk of the patient developing a dependence upon these agents, it is generally felt that nicotine per se is not carcinogenic and that dependence upon nicotine gum involves far less exposure to toxic substances than does cigarette smoking. However, this caveat may be less comforting to the pregnant woman, because nicotine has not been proved to be without serious consequences to the fetus. As is pointed out in the accompanying editorial, the availability of medications that do not contain nicotine provides physicians with new therapeutic options.1
This is the largest trial of the use of an antidepressant in this setting, although other antidepressants, particularly nortriptyline, have also been shown to increase cessation rates.2 Why might antidepressant therapy increase rates of smoking cessation? Nicotine activates central nervous system pathways to release norepinephrine, dopamine, and other neurotransmitters. It elevates dopamine levels in areas of the brain associated with the reinforcement properties of cocaine and opiates. Antidepressants may work by inhibiting the neuronal uptake of norepinephrine and dopamine in these critical brain areas and thereby lessening the effects of nicotine withdrawal. Antidepressant therapy has no risk of dependence and is very safe. Since smokers are more likely to have a history of depression than nonsmokers and cases of psychotic depression after smoking cessation have been reported, the use of an antidepressant as an adjunct to smoking cessation efforts makes sense. Given the relative safety of antidepressants during pregnancy, the more prudent course for smoking cessation in pregnant women might be the use of an antidepressant in preference to a nicotine patch.3,4 Another important option to enhance the likelihood of quitting is to arrange for high-intensity behavioral therapy by contacting the local chapter of the American Cancer Society or the American Lung Association. The only unacceptable approach is to avoid the issue.
1. Benowitz NL. N Engl J Med 1997;337:1228-1229.
2. Humfleet G, et al. In: Harris LS, ed. Problems of Drug Dependence 1995: Proceedings of the 57th Annual Scientific MeetingThe College on Problems of Drug Dependence. Government Printing Office; 1996:334.
3. Nulman I, et al. N Engl J Med 1997;336:258-262.
4. Chambers CD, et al. N Engl J Med 1996;335:1010-1015.