About 40 percent of America's 50 million smokers will try to kick the habit at least once this year. On average, fewer than one in 10 will succeed.

The best time to quit is now. There are seven drug treatments and a host of smoking cessation programs available to help smokers kick the habit.(BY MARK NOWLIN / THE SEATTLE TIMES)The numbers sound discouraging. But addiction researchers offer the offsetting news that there's never been a better time to quit. (And there's never been more financial incentive: Washington state's cigarette tax hit $1.42 a pack, the highest in the nation, on Jan. 1.) While 10 years ago the only options for would-be quitters were nicotine gum or going cold turkey, now there are a host of scientifically validated methods. These include seven drug treatments, as well as many organized smoking cessation programs and individual counseling services. Four safe and proven nicotine replacement methods — gum, a patch that delivers nicotine through the skin, an inhaler that mimics the effect of smoking and a spray that provides a quick burst of nicotine to nasal passages — can deliver gradually declining doses to take the edge off cravings and withdrawal pangs. They have only minimal side effects, a low risk of addiction and are free of the nearly 4,000 harmful substances that cigarette smoke delivers. An antidepressant medication — bupropion, marketed for depression under the brand name Wellbutrin and for smoking cessation as Zyban — can also help break cigarette addiction, though the scientific process by which this occurs is still not understood. There have been reports from Europe of serious adverse effects, including some deaths, from Zyban. Several professional societies are reviewing the data. "It's unclear if the events are related to the medication," says John Hughes, psychiatry professor at the University of Vermont. For especially difficult cases, clonidine and nortriptyline, a blood-pressure medication and an antidepressant, respectively, are two options. The evidence of their value is not as extensive as that for nicotine-replacement drugs, but a government panel advised recently that these medications be tried if other drugs have failed. (Neither, however, is approved for this use by the Food and Drug Administration). A new generation of drugs also is in the research pipeline, including a tobacco vaccine currently under development. Success is being found, too, on the behavioral front, with self-directed software programs (see story on E 3) and toll-free telephone hotlines for smokers trying to quit. Pleasure-reward pathway No one suggests that quitting is easy, even with medications. "It takes just a few heartbeats to get nicotine from the tip of your finger to the brain," says Richard Hurt, director of the Nicotine Dependence Center at the Mayo Clinic in Rochester, Minn. Once there, nicotine produces significant changes in brain cells. Chemically similar to naturally occurring neurotransmitters or chemical messengers, nicotine displaces some brain chemicals. Just 10 days of smoking triples the number of entry points — receptors — that allow nicotine to get inside brain cells. There, nicotine acts on the pleasure-reward pathway by raising levels of four key neurochemicals that affect alertness, energy and mood — dopamine, norepinephrine, beta endorphins and serotonin. (Newer antidepressant medications target levels of these same brain chemicals.) Research published last month shows that nicotine also disables a regulatory mechanism that limits the pleasure system. Result: The reward system is turned on right away and keeps sending reward signals for 60 minutes, even though the nicotine levels drop off 15 minutes after smoking. That's why the development of effective nicotine-replacement drugs has finally given an edge to would-be quitters. Using one or more of these medications boosts success rates to about 25 percent. Close monitoring of withdrawal symptoms and tailoring nicotine-replacement therapy to the individual have produced success rates of up to 50 percent at some of the best smoking-cessation programs. In the community at large, however, research suggests that both smokers and some physicians are confused about what approach to use. "The challenge is finding the right combination for each individual," says Neil Grunberg, professor of psychology and neuroscience at the Uniformed Services University of the Health Sciences in Bethesda, Md. (See chart on E 3 for pros and cons of methods, and what research suggests about who might benefit most from each method.) 'Tough it out' Despite the expanded choices, smokers often think the habit is a character weakness, so they should "tough it out" and go cold turkey. They don't take advantage of the medications proven to help assuage the strong physiological symptoms of withdrawal, or they use too little. "That is why there is such a high relapse rate," explains David Sachs, clinical associate professor of pulmonary and critical-care medicine at Stanford University School of Medicine. "It's like killing all four engines on a Boeing 747 when you're 2,000 feet above the runway." Underdosing can sabotage the most dedicated attempts to quit. At Stanford, Sachs and his colleagues monitored the blood levels of nicotine as smokers quit and compared them with the eventual rates of success. When nicotine levels dropped too precipitously, to 50 percent or less of what they had been while participants were smoking, success rates were no better than the 5 to 8 percent seen with a placebo, about equivalent to going cold turkey. Another mistake smokers make is ignoring the importance of behavior therapy or social support. The federal treatment guidelines found that only a combination approach — proper doses of medication along with professional and/or social support — can consistently push the success rates to about 30 percent. More than willpower There is, fortunately, a growing recognition that smoking is not a weakness but an addiction, and a serious chronic disease that warrants treatment. "We wouldn't tell someone with a blood sugar of 500 to (just) work on their willpower," says Michael Fiore, chairman of a federal panel that issued treatment guidelines two years ago calling for nearly every smoker who wanted to quit to use medications. "We don't tell someone who has a systolic blood pressure of 250 that if they really had character they could control it on their own." And yet Medicare doesn't pay for smoking-cessation medications, and only about half of private insurers do (health-maintenance organizations often do). But the bottom line that tobacco experts are delivering is this: Smokers should keep trying to quit no matter what the cost. Giving up cigarettes at age 50 cuts in half the risk of dying from smoking-related illnesses during the next 15 years, Fiore says. Even so-called "failures" — people who quit for days or weeks but go back to smoking — stand a good chance of succeeding ultimately. Studies show that being able to stay off cigarettes for a week is strongly linked — eventually — to long-term quitting. "Keep trying; a lot of people give up too soon," says Hughes, the Vermont psychiatrist. "The No. 1 message is that there is a lot of help out there now."

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