More Good News on Zyban and Smoking

Sept. 20, 2001 -- If fear of weight gain keeps you smoking, here's encouraging news: The antidepressant Zyban (also known as Wellbutrin or by its generic name bupropion) has helped many people quit. Now, research shows the drug seems to prevent relapse and even seems to help women lose weight.

For smokers who try to stop, 70% to 80% relapse within the first year, despite treatment advances. That's a big problem, says J. Taylor Hays, MD, associate director of the Mayo Clinic Nicotine Dependence Center.

Many women fear they will gain weight so they don't even try to kick the habit, he tells WebMD. "That's especially typical in young women," he says, adding that with this drug, "It's one potential barrier we could remove."

In his study of nearly 800 men and women (all of whom smoked at least 15 cigarettes a day), 461 successfully stopped after seven weeks on the drug. Half of that group continued taking it for a year, and the other half took a placebo. All received counseling typical of smoking cessation programs.

The results: "People on bupropion [Zyban] did not relapse as often as those taking placebo," Hays tells WebMD. At the end of the first year, 55% of the Zyban group was still smoke-free. However, two years later, similar numbers of the Zyban and non-Zyban groups had relapsed.

"While the drug was being used, relapse was less frequent, so it does have an effect in delaying or preventing relapse," Hays tells WebMD. "Unfortunately, it was not something that persisted."

When the drug is used to treat depression, longer-term treatment has shown to prevent relapse, he says. "This may be true with smoking cessation, too. It looks like a drug that's safe to take for the long term."

Those in the study were "already rather thin" and were not asked to change their diets or exercise schedules, he says. Yet his study presented cheery news for those concerned about weight gain.

"Women in both groups gained some weight, but the drug group gained less weight," says Hays. "Two years later, they still had significantly less weight gain."

The second study, which looked at women trying to lose weight, showed "very impressive" weight loss, says lead author Kishore Gadde, MD, director of obesity clinical trials at Duke University Medical Center.

His study involved 50 women. None were clinically depressed. Participants were randomly assigned to groups getting either Zyban or a dummy pill used for comparison. Only the researchers knew which participants were receiving the medicine. And the investigators seem pleased with the results.

"I was convinced weight loss was an independent effect of the drug," says Gadde.

For the first eight weeks, half got Zyban, half got the placebo. Both groups were told to follow a 1,600 calorie-per-day diet, which was "very liberal," Gadde tells WebMD. "A low-calorie tends be 1,200 calories."

The drug proved to be four times better than the placebo, he says. At the end of eight weeks, 16 people had lost at least 5% of their initial weight. "It's hard to lose that much weight so fast," he says.

In the second part of the study, 14 participants taking the drug lost an average of 13% of their initial weight, a result that Gadde calls very impressive.

"You don't expect to lose that much with simple diet prescription of 1,600 calories, so it must be the drug that's working."

He followed that group for another two years. "I'm a skeptical guy," he tells WebMD. "The ... effect was not just a flash in the pan; it continued to work."

Best of all, 74% of the weight loss came from losing fat, not muscle. And half the fat loss was in the trunk region -- "where people want to lose it," he says. Plus, there was no loss of bone density, another serious concern because of increased risk of osteoporosis.

Also, those taking the drug were more likely to stick to the diet and keep track of what they ate, he says.

The drug, which has been FDA-approved for several years, has not shown to carry any risks of heart damage, a big concern with the diet drug Redux, which was eventually pulled from the market. Zyban has few side effects and is not recommended for people with history of seizures, bulimia, or anorexia, Gadde tells WebMD.

Gadde and Hays say that researchers are still debating just how Zyban works to curb nicotine addiction and obesity.

"As with other so-called psychoactive substances, we don't know quite how or why it works," Hays tells WebMD.

Researchers believe the drug increases levels of two chemicals in the brain, dopamine and norepinephrine, which enhance feelings of pleasure.

"Perhaps the satiety that's received from food is related to dopamine activity," says Hays. "People who don't have enough dopamine tend to overeat, and those with higher dopamine levels reduce intake. This is a consistent explanation with nicotine addiction."

"Whether or not that theory actually pans out, we don't yet know," he says.

Both studies were supported by research grants from Glaxo Wellcome (now GlaxoSmithKline), maker of Zyban.