Smoking less as a treatment goal for those who cannot stop smoking

Most smokers would like to quit smoking. However, because they are addicted to nicotine, only a small percentage (less than 3%) successfully quit each year. Quitting is especially difficult for heavy smokers who are more highly addicted. Many highly addicted smokers have failed multiple quit attempts. For such smokers who cannot quit, reducing the harm from smoking is desirable. The idea of harm reduction for smokers who are unable to quit has been a topic of a recent Institute of Medicine report and a recent national conference (1,2). Several approaches to harm reduction have been considered. These include novel tobacco or nicotine products that reduce exposure to tobacco toxins, interventions to reduce cigarette consumption and chemoprevention to reduce disease risk from smoking. The paper by Hatsukami and coworkers in this issue of the Journal examines the proposition that smokers can reduce their cigarette consumption with the aid of medication (3). Previous research on this topic has focused on nicotine medications (4). Nicotine in pharmaceutical form is expected to replace the nicotine obtained from cigarette smoke, so that smokers can obtain their requisite daily dose of nicotine while smoking fewer cigarettes. Other drugs used for smoking cessation, such as bupropion, might also be useful to reduce smoking. Bupropion is believed to work by mimicking the effects of nicotine by releasing key neurotransmitters, such as dopamine and norepinephrine, and/or by antagonizing actions of nicotine on the nicotine receptor (5,6). Conceivably, bupropion would block some of the rewarding effects of nicotine from tobacco while at the same time exerting neurochemical effects that simulate the desirable effects of nicotine. Medications that reduce smoking could have two benefits. One benefit is, of course, to reduce smoke exposure and therefore reduce the health risks from tobacco use. Two small studies of short duration suggest possible benefits of smoking reduction. Mahmarian found that when smokers with severe coronary artery disease use nicotine patches, they reduce their level of cigarette smoking, which results in a substantial reduction in the extent of exercise-induced ischemia, as measured by nuclear perfusion studies (7). Rennard et al found that smoking reduction with the help of nicotine gum was associated with decreased respiratory tract inflammation as assessed by bronchoalveolar lavage (8). A second potential benefit of smoking less is that smokers would reduce their level of nicotine dependence and gain confidence in their ability to control their smoking behavior, which would then result in a greater interest and success in quitting. In this issue of the Journal, Hatsukami and colleagues present the results of a multicenter, placebo-controlled trial of the use of bupropion to reduce smoking in smokers who were uninterested or perceived themselves as unable to quit. Outcome measures included the selfreported level of reduction of cigarette smoking, biochemical assessment of tobacco smoke exposure, and interest and success in smoking cessation. The results of this trial are both promising and disappointing. The Hatsukami study was designed with a target of a 50% reduction in cigarette smoking among highly dependent smokers. These were smokers of at least 20 cigarettes per day who had failed two or more previous quit attempts. Subjects received either bupropion or placebo, and all subjects received monthly counseling on cigarette reduction. The reduction phase was planned for 6 months, but at any time a smoker decided that he or she would like to quit, the reduction phase was discontinued, and the subject was entered into a cessation program. Smoking cessation treatment included an additional 7 weeks of medication and counseling, and a treatment manual. The study design is a realistic one that reflects what would probably occur in a smoking reduction program conducted in a clinical practice. The promising results of the Hatsukami study were that some smokers did reduce their cigarette consumption and their tobacco smoke exposure while taking bupropion, and a sizable percentage of the smokers decided to make a quit attempt. The disappointing aspects of the study were that many smokers did not substantially reduce their smoking and that overall the extent of the reduction of smoke exposure, as assessed by biochemical markers, was quite modest. Among those who were able to reduce their smoking at 3 and 6 months, few sustained that reduction when assessed at 12 months. Furthermore, Am J Med. 2004;116:203–205. From the Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, the Departments of Medicine, Psychiatry, and Biopharmaceutical Sciences, University of California, San Francisco. The author is supported by grants DA02277 and DA12393 from the U.S. Public Health Service, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland. He is an occasional paid consultant to pharmaceutical companies that manufacture and market medications to aid smoking cessation including nicotine products. Requests for reprints should be addressed to Neal L. Benowitz, MD, Chief, Clinical Pharmacology and Experimental Therapeutics, University of California San Francisco, Box 1220, San Francisco, California 94143-1220, or nbeno@itsa.ucsf.edu.