About 40 percent of America's 50 million smokers will try to kick the habit at least once this year, according to the federal Centers for Disease Control and Prevention (CDC). On each attempt, fewer than one in 10 will succeed. As discouraging as those nu

"Most people have to try to quit probably five to seven times before they succeed," said John Hughes, professor of psychiatry at the University of Vermont. "It's just like swimming -- it's important to keep jumping in the water to learn." And as experts like to note, there has never been a better time to quit -- or so many different scientifically validated options to help smokers reduce the pangs of nicotine withdrawal and the craving for cigarettes, both of which make quitting smoking harder than making most other behavioral changes. (To help prompt smokers to make the effort and to limit exposure of non-smokers to cigarette smoke, 82 percent of work sites in the District are smoke-free, 43 states restrict smoking in government offices and 21 restrict smoking in private work places, according to the CDC.) Ten years ago, "all we had to offer was going cold turkey or nicotine gum," says Michael C. 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 to support their efforts. Today, there are seven drug treatment choices, as well as many organized smoking cessation programs and individual counseling services that also boost chances that smokers will manage to quit. 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. They have only minimal side effects, a very low risk of addiction and are free of the nearly 4,000 harmful substances that cigarette smoke delivers. The treatments don't end there. 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 many reports of serious adverse effects, including some deaths, from Zyban in Europe. Next week, several professional societies will review the data. But for now, "it's unclear if the events are related to the medication," says Hughes. Two other options for especially difficult cases of smoking addiction are the blood pressure medication clonidine and the antidepressant nortriptyline. While the evidence of their value is not as extensive as that for nicotine replacement drugs, 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). "The good news for smokers," Fiore says, "is that people now have a choice. There's never been a better time to quit." Trouble is, a lot of smokers do it the wrong way and increase their odds of failure. Since smoking is often viewed as a weakness or character flaw, many smokers tend to tough it out themselves and go cold turkey. Or they mistakenly use minimal amounts of the nicotine replacement drugs and other medications that are proven scientifically to help assuage the strong physiological symptoms of withdrawal. "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 in California. "It's like killing all four engines on a Boeing 747 where you're 2,000 feet above the runway. You crash and burn and then people start beating up on themselves. They say, 'I am a failure,' when they are really dealing with something that has a striking rationale as far as pharmacology and physiology are concerned." "Well, I am back again. They say that the third time's a charm. Hope they are right. This is the third time this year that I am quitting. The last time I went back to smoking, I got so depressed that I didn't want to talk to anyone for a long time. Can't say I will make it, can't say I won't. I'm just going to take this one minute, hour and day at a time.'' -- Quitnet.com posting from a smoker planning to give up cigarettes on Feb. 13. No one suggests that quitting is easy, even with nicotine replacement medications. Adult smokers go through an average of a pack of cigarettes each day. At 20 cigarettes per pack and 10 puffs per cigarette, that's 200 nicotine hits a day right to the brain, making smoking "one of the world's most intense habits," says the University of Vermont's Hughes.The cigarette is one of the fastest and most powerful drug delivery systems ever known. "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, says Stanford's Sachs. 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.) "The bottom line is that nicotine has a lot of very beneficial effects on how we feel and think," Sachs says. That's why the development of effective nicotine replacement drugs has finally given an edge to smokers who want to quit. Using one or more of these medications boosts success rates to about 25 percent, the federal treatment guidelines issued in 2000 by the Agency for Healthcare Research and Quality (AHRQ) found. Evidence suggests they could go higher if more intensive treatment and greater support were applied. Close monitoring of withdrawal symptoms and tailoring nicotine replacement therapy to the individual has produced success rates of up to 50 percent at some of the best smoking cessation programs. At Mayo's Nicotine Dependence Center, for instance, smokers pay $3,300 each to check into an intensive, weeklong residential smoking cessation program. They undergo blood testing for cotinine, a marker of nicotine byproducts; the tests are used to help adjust treatment individually for withdrawal symptoms and cravings. The program includes daily group and individual therapy, stress reduction, nutrition and diet information, supervised exercise and a 12-step program similar to Alcoholics Anonymous. About 700 smokers have gone through the decade-old program, which attracts long-term older smokers -- average age 53 compared with early forties for other programs -- who have tried to quit on numerous occasions. Eighty percent of the participants are already experiencing tobacco-related illnesses such as emphysema or heart disease. Yet, one year after treatment -- the longest follow-up data available -- about 45 percent of participants remain smoke-free, according to Hurt. At Stanford, Sachs and his colleagues have also found that an individualized outpatient approach can be effective, boosting quitting success rates to 50 percent. Both programs, Hurt says, show the kind of results that could be expected "if the federal guidelines were fully implemented with more intensive treatment for smokers." In the community at large, however, research suggests that both smokers and some physicians are confused about what approach to use. "While we are blessed with a variety of treatment strategies, 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. Science still can't say with certainty which smoker will benefit most from which treatment, but there are tantalizing hints. "Men seem to do better [than women] with nicotine gum and the patches," Grunberg says. Studies suggest that bupropion works equally well in men and women and is especially helpful for smokers with a past history of depression, according to Fiore. The 2000 treatment guidelines, which were written after an extensive review of the scientific literature, note that gum and bupropion seem to help prevent weight gain. Those who have experienced severe withdrawal symptoms in previous attempts to quit may do better on the patch; studies suggest that smokers who suffer severe cravings seem to be helped by the high-speed nicotine delivery of the gum, the inhaler or the nasal spray. Yet all too often, tobacco addiction experts find that smokers go cold turkey and don't take advantage of these aids -- an almost-certain program for failure. Or they don't follow directions and use too little of the medications to help them succeed, perhaps because the treatment can cost $4 to $18 a day -- compared with $3.50 for a pack-a-day habit. "Most people are way under-dosed," Hurt says. "If they're getting more than 300 milligrams a day from cigarettes -- that's about two packs a day -- then we will use two [nicotine replacement] patches." Not using enough nicotine replacement medication can sabotage the most dedicated attempts to give up smoking. 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. Smokers need to take a cue from other over-the-counter medications. "They say: If your symptoms persist for a few days, go see your doctor," Sachs notes. "What nicotine replacement products should say is: If craving for cigarettes continues or you experience increased irritability or difficulty concentrating, contact your doctor. As a physician, that would tell me that you're probably not getting an effective dose." Another mistake smokers make is thinking of nicotine replacement as a magic bullet that will help them sail through the difficult days of withdrawal and ease their cravings without any additional effort. Those who ignore the importance of behavior change or social support undermine their efforts. The federal treatment guidelines found that only the combination approach -- proper doses of medication along with professional and/or social support can consistently push the success rates to about 30 percent. "You should not approach taking a smoking cessation medication the way you would approach taking an antibiotic or a painkiller," Grunberg says. "These medications do not work on their own." Looking back over my one month [of abstinence], I find that the one constant lesson I've learned from everything I've seen is that I can't have one puff!'' -- Feb. 1 posting on quitnet.com from a 60-year-old who has smoked for 47 years. For those trying to quit, there's no safe way to light up a single cigarette -- which is why the current treatment guidelines advise abstinence. Some nicotine replacement medications, such as the patch, could contribute to toxic levels of nicotine if they are combined with smoking and lead to nausea, blood pressure problems and other health effects. But worse, even one cigarette can send a smoker down a slippery slope toward re-addiction. "There's never a point where there is an absolute guarantee that someone has quit smoking," says Harry Lando, professor of epidemiology at the University of Minnesota's School of Public Health and a member of the federal committee that drafted the treatment guidelines. It is true, however, that the longer abstinence is achieved, the better the chance that it will be permanent. Large population studies show that smokers who quit for a year have an 85 percent chance of maintaining their abstinence, Lando says. Those who make it five years have a 97 percent chance of continued success. "But it's important that someone not feel too safe and let down their guard," Lando says. "I have a colleague, a professional in the health area, who had not smoked for 16 years. He ran into marital difficulties and a serious health issue with a child and went back to smoking and has not yet been able to quit." However difficult it may be to quit, smoking researchers are convinced that nearly everyone can achieve independence from smoking -- given the right help. A new generation of drugs now in the research pipeline -- such as a tobacco vaccine currently under development at Nabi in Rockville -- is expected to attack tobacco dependence in bold new ways. The $206 billion settlement by state attorneys general with the tobacco companies established the American Legacy Foundation in 1999. The foundation is pumping dollars into prevention programs and into practical strategies, including $7.5 million for the establishment of a toll-free telephone hot line for pregnant smokers trying to kick the habit (1-866-66-START). "We know that quit lines can be an effective way to help people quit smoking," says Scott Leischow, chief of the National Cancer Institute's tobacco control branch. [See "Plot a Winning Strategy," below, for more information on quit lines]. But these help lines are still only available in 28 states. The District, Maryland and Virginia are among the jurisdictions that don't yet offer quit lines. There's also a growing recognition that smoking is not a character flaw or 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," Fiore says. "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. Why hold back treatments from smokers that we know could help?" And yet that is essentially what happens every year. Medicare doesn't pay for smoking cessation medications, and only about half of private insurers cover such treatment, although health maintenance organizations often do. "It's important that smokers, doctors, insurers and the U.S. Congress hear what a paradox it is that our health system spends tens of billions of dollars to provide care for heart attacks or strokes or lung cancer or emphysema, but it does not pay for medicine that could help people quit smoking," Fiore says. "Not too many PPOs [preferred provider organizations] cover it and I don't know why," says Walter Cherniak, Mid-Atlantic public relations manager for Aetna, whose PPOs do not cover cessation but whose HMOs do. "But prevention and health promotion are the biggest advantages of belonging to an HMO." 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 the risk of dying in half from smoking related illnesses during the next 15 years, Fiore says. Even long-term smokers who have been diagnosed with smoking-related health effects -- chronic obstructive pulmonary disease or lung cancer -- can buy time and improve breathing capacity by as much as 5 percent by quitting. "In someone who is oxygen-impaired, that really makes a difference," Fiore says. Continuing to try to cut the dependence on smoking can help save lives and health care dollars, according to a 1997 report by the agency now known as AHRQ. Providing smoking interventions to 75 percent of U.S. smokers 18 and older would cost $6.3 billion for the first year, but would produce 1.7 million new quitters, the report said. 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. "The message is: Keep trying," says the University of Vermont's Hughes. "A lot of people give up too soon. The number one message is that there is a lot of help out there now."

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