For many smokers, the last time they tried to quit was November 20, 1997--the annual Great American Smokeout. Since 1977, the American Cancer Society has sponsored the event in which smokers are urged to put away their tobacco for 24 hours.

The Smokeout has been a successful tool for encouraging smokers to quit. The September 19, 1997 issue of the Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report reported that in 1996 the advertising blitz accompanying the event reached two out of every three smokers. And the percentage of smokers who said they stopped grew from 18 percent in 1995 to 26 percent in 1996.

The trouble is that only a small percentage of those people stay off smoking for more than a day. Although 70 percent of adult smokers insist that they want to give it up, the addictive power of nicotine overwhelms the will power of most; fewer than 10 percent of attempts to quit are successful.

This year's crop of hopeful ex-smokers may better those odds, however. Last May, the Food and Drug Administration approved a new indication for a little-known prescription antidepressant called bupropion. Studies submitted to the FDA by the drug's manufacturer, Glaxo Wellcome Inc., had shown that it reduced the craving for nicotine. What made the drug unique is that it was the first apparent quitting aid that did not simply substitute nicotine in another form for tobacco.

Without question, nicotine replacements have eased quitting for millions of smokers. Drugmakers have made nicotine available in a range of delivery systems, from transdermal patches to chewing gum and inhalers. Once costly prescription drugs, most are now readily available over-the-counter. Even the tobacco industry has been trying to improve its "delivery system" so that it doesn't release smoke.

On the other hand, bupropion, which is being marketed as a smoking cessation aid under the tradename Zyban, acts by a totally different mechanism. Researchers suspect that it works directly in the brain to disrupt the addictive power of nicotine by affecting the same chemical messengers in the brain, such as the neurotransmitter dopamine, as nicotine does. "Release of dopamine is involved in the pleasure response of drugs of addiction, such as nicotine and cocaine," says Richard Hurt, director of the Mayo Nicotine Dependence Center. "Bupropion probably increases the amount of dopamine in the brain, although not nearly to the level of smoking. Smoking floods the brain with dopamine."

Whatever its mode of action, Zyban clearly works, as Hurt and his colleagues demonstrated in a paper published in the October 23 issue of the New England Journal of Medicine. The study of more than 600 smokers compared three different doses of the drug and a placebo over seven weeks. At the end of treatment, 44 percent of those who took the highest dose of the drug (300 mg) were not smoking, compared to 19 percent of the group who took a placebo. By the end of one year, 23 percent of the 300 mg group and 12 percent of the placebo group were still smoke-free.

mage: Food and Drug Administration, based on data from the Centers for Disease Control

Nor does the apparent effectiveness of Zyban rule out nicotine replacements. Indeed, using both methods seems to improve the quit rate a bit further. Four-week quit rates from the study were 23 percent for placebo; 36 percent for the patch; 49 percent for Zyban; and 58 percent for the combination of Zyban and the patch.

Zyban is just another sign that neuroscientists are getting closer to an understanding of addiction on a molecular level. Like many drugs in new indications, its effect was discovered by accident: researchers knew that quitting smokers were often depressed, and so they began experimenting with the drug as a means to alleviate depression, not addiction. Other pharmaceutical firms are pursuing similar drugs. Eli Lilly and Co. is testing an experimental compound, designated LY333068, which is an antagonist to serotonin, another neurotransmitter that plays a role in addiction and in depression.

Meanwhile, evidence that smoking is one of the most dangerous addictions known continues to accumulate. Researchers have recently identified the first molecular evidence linking a specific compound in cigarette smoke directly to lung cancer. They have also established a connection between smoking and rheumatoid arthritis, and presented evidence that smoking even contributes to hip fractures.

"Tobacco use in 1997 is not just some bad habit, but a powerful addiction that warrants appropriate medical treatment," says Michael Fiore, M.D., director of the Center for Tobacco Research and Intervention at the University of Wisconsin Medical School. Kicking the habit will still require a commitment, but hopefully, new approaches to treatment will ease the process.


Agency for Health Care Policy and Research

American Heart Association

American Cancer Society

American Lung Association

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