THE QUIT-SMOKING PILL ANTIDEPRESSANT BUPROPION WORKS ON THE BRAIN TO HELP KICK THE HABIT.

Byline: Mariko Thompson Staff Writer

Sharon Grosskopf must have tried to quit smoking at least 20 times. Name the method and the 62-year-old Simi Valley resident has done it - quitting cold turkey, popping hard candies, chewing nicotine gum, slapping nicotine patches on her arm.

Even when she weathered the physical withdrawal, the psychological craving for a cigarette overwhelmed her resolve. So Grosskopf had no qualms when her doctor suggested taking an antidepressant medication called bupropion.

``I didn't care what it was as long as it worked,'' she said. ``I've heard that quitting smoking is harder than getting off heroin. I don't know if that's true, but it is difficult.''

For Grosskopf, bupropion accomplished what other methods could not. Except for a brief relapse after a death in the family, Grosskopf has been cigarette-free for five years.

Bupropion - sold as Zyban and Wellbutrin SR - has emerged as a front- line treatment since receiving approval as a smoking cessation aid by the Food and Drug Administration in 1997. Researchers speculate that bupropion stimulates the brain in a way similar to nicotine, triggering certain chemicals such as dopamine.

``The release of dopamine has been associated with reward,'' said Dr. Arthur Brody, associate professor at UCLA's Neuropsychiatric Institute. ``It is a pleasurable experience.''

Other antidepressants 

Bupropion isn't the only antidepressant that curbs nicotine cravings. Nortriptyline also appears to affect the brain in the same way, but doctors say the drug has more severe side effects. Antidepressants such as Prozac have not proven as effective for smoking cessation, they say.

Bupropion isn't a miracle pill. It doesn't work for every smoker. Still, a 1999 study published in the New England Journal of Medicine found bupropion was more effective than the nicotine patch or a placebo. Just over 30 percent of the bupropion group abstained from smoking for one year, compared to 16 percent of patch users and 15 percent of the placebo group. The numbers improved to 35 percent among those who combined bupropion and the patch. The study excluded smokers who had been diagnosed with depression.

Not every doctor is a fan of popping pills, even for such a benevolent cause as smoking cessation. Dr. Gordon Dowds, a pulmonologist at West Hills Hospital, only recommends bupropion to patients who need to quit but have great difficulty doing so. Dowds favors behavioral strategies, such as writing down the reason for each cigarette smoked or locking the pack in the trunk of one's car.

``I have a stop-smoking kit,'' Dowds said. ``It's a mirror. If you want to see your face looking back at you, quit smoking. I've never been terribly impressed with any drug therapy. There comes a day, whether it's Wellbutrin or Nicorette, that you have to stop. On that day, you will still have a craving.''

At Kaiser Permanente in Woodland Hills, patients who seek a prescription for bupropion are required to enroll in a five-week smoking cessation course that teaches behavioral strategies. While antidepressants aren't the answer, they are a useful tool, said Dr. Stanley Gold, a Kaiser Permanente psychiatrist.

``Medication in and of itself won't change the behavioral pattern,'' he said. ``To change those patterns takes practice and exercise.''

Gold said he prefers bupropion over the nicotine patch. The release of brain chemicals gives patients the pleasurable sensation that they crave without putting more nicotine into their bodies. Though more than 50 deaths have been reported in the United Kingdom among bupropion users, data in the U.S. has not raised similar concerns, he said.

Typically, patients will take bupropion about one to two weeks before they quit smoking. After they quit, patients remain on the medication for a few months. Brody, who also directs smoking cessation programs for the VA Greater Los Angeles Health Care System, will leave patients on antidepressant medication longer if they fear a relapse.

``To the best of my knowledge, it's safer to be on bupropion long-term than to smoke long-term,'' Brody said.

Why should you quit?

About 440,000 Americans die from smoking-related diseases each year, according to the American Lung Association. From a health standpoint, it's never too late to quit. After one year, risk of heart disease returns to normal. Cancer risk also declines. Compared to nonsmokers, former smokers face twice the risk of lung cancer while smokers have 10 times the risk, said William McCarthy, chair of the American Cancer Society's regional nutrition and physical activity committee.

``It's an illustration of how widespread and profound the impact of tobacco is on health,'' McCarthy said.

An estimated 45 million Americans have quit smoking. Another 46.5 million still smoke. On average, former smokers make five attempts to quit before they're successful. The trick is to examine the failures and learn from them, experts say.

Some people will succeed using only one treatment method, but most require a combination. Front-line treatments include behavioral strategies, group or individual therapy, nicotine replacement and antidepressants. Brody recommends which combination to use based on the patient's smoking habits and past experiences with quitting.

``The one thing that's definitely known, more treatment is better than less treatment,'' Brody said. ``The more treatment they get, the more likely they are to quit. If someone tries the patch over the counter, their chances of quitting are not as great as if they had tried the patch and group therapy.''

Addicted at 16

Grosskopf had no idea that smoking was bad for her when she took her first puff at age 16. She still remembers her first cigarette. Her father let her drive the family car by herself for the first time. She and some girlfriends went shopping in Pasadena. A police officer caught them jaywalking across a street and issued tickets.

``We thought this was a terrible thing and we were scared,'' Grosskopf recalled. ``One girlfriend said, 'Let's get a pack of cigarettes, it calms your nerves.' We bought a pack of cigarettes from a vending machine and that was that.''

It took 46 years for Grosskopf to win the battle against cigarettes. She took the lavender bupropion pills for one week, then quit smoking. She still wanted a cigarette, but she no longer felt an all-consuming craving.

Today, Grosskopf can feel the difference. It's easier to breathe. And she doesn't develop bronchitis every time she catches a cold.

``I feel better about myself now that smoking doesn't dictate my life,'' she said.

Box

Number of Americans in 1999 who had quit smoking: 45.7 million

Number of Americans who still smoke: 46.5 million

Percentage of smokers who began smoking before turning 21: 90

Number of deaths in the U.S. attributed to smoking each year: approximately one in five or about 440,000 people

Number of distinct cancer-causing chemicals in cigarettes: 43

Percentage of lung cancer cases attributed to smoking: 87

Source: American Lung Association

Facts about bupropion

What it is: Bupropion is an antidepressant sold as Zyban or Wellbutrin SR. It has become a front-line treatment for smoking cessation. Other alternatives include behavioral strategies, group or individual counseling, and nicotine replacement products in the form of patches, gums, inhalers and lozenges. Experts in smoking cessation often recommend a combination of treatments to overcome the addiction.

How it works: Researchers believe bupropion, which contains no nicotine, curbs the craving for cigarettes by triggering the same rush of brain chemicals. Bupropion is the only antidepressant approved by the Food and Drug Administration for smoking cessation.

Who shouldn't take it: It should be avoided by pregnant women, those taking other antidepressant medications, and people with a history of seizures, eating disorders, or liver and kidney problems. Common side effects include insomnia and dry mouth. The medication also increases the risk of high blood pressure.

CAPTION(S):

4 photos, 2 boxes

Photo:

(1 -- 2 -- color) Stop it!

Antidepressant bupropion helping longtime smokers kick the habit

Photo illustration by Andy Holzman and Shane Michael Kidder/Staff Photographers

(3) Sharon Grosskopf, 62, below, who quit by taking bupropion

(4) no caption (Bupropion smashing cigarettes)

Box:

(1) Box (see text)

(2) Facts about bupropion (see text)