Smoking Cessation — A Practical Guide for the Primary Care Physician
Smoking Cessation—A Practical Guide for the Primary Care Physician
Author: Gregory R. Wise, MD, FACP, CPE, CPHQ, Associate Professor of Medicine, Wright State University School of Medicine, Medical Director, Kettering Medical Center Tobacco Treatment Center, Dayton, OH
Peer Reviewer: Tammy Sims, MD, MS, Assistant Professor of Pediatrics and Center for Tobacco Research an Intervention, University of Wisconsin School of Medicine and Public Health, Madison.
Issue Editor: Robert B. Taylor, MD, Professor Emeritus, Department of Family Medicine, Oregon Health Sciences University School of Medicine, Portland.
"Yes, we agree that smoking cigarettes, including our brands, causes lung cancer and other serious diseases in smokers." —Thomas Dubois, Corporate Affairs, Philip Morris Australia, 20021
The escalating consumption of tobacco products is creating an unprecedented worldwide pandemic that in the 21st century will result in 1 billion deaths worldwide. No other disease or condition comes even close to the horrific personal, economic, and health consequences of nicotine addiction. Tobacco companies produce 5.5 trillion cigarettes per year—nearly 900 cigarettes per year for every man, woman and child in the world!2 In the United States, the primary care physician is often the first line of clinical contact in identifying tobacco dependence, assessing willingness to quit, and providing effective smoking-cessation support and treatment. The primary care physician can also serve as a catalyst for political change."
This issue will address the practical aspects of smoking cessation intervention and will provide useful references to web-based resources to help both the patient and the physician.
—The Editor
The Challenge
Many primary care physicians over the years have become jaded and skeptical of the success of tobacco cessation interventions. The perceived reasons are legion: patients may not be motivated to quit, patients may be more concerned about their other medical issues, treatment modalities have not been viewed as affordable or effective, and the high recidivism can be demoralizing for both the patient and physician. A survey of more than 3000 U.S. family physicians, internists, OB/GYNs, and psychiatrists was sponsored by the American Legacy Foundation and conducted by the American Association of Medical Colleges.3 The September 2006 report concluded that "many physicians lacked knowledge about smoking cessation services and often failed to offer enough encouragement or moral support to patients attempting to quit."
Despite this report, in recent years several factors have developed that make tobacco cessation efforts a more practical option than in the past. More than a dozen states in the United States now have clean indoor air ordinances. Washington, D.C. went smokefree on January 1, 2007. This U.S. momentum is being paralleled by an international movement as entire countries such as Ireland, Spain, Uruguay, England and France are either now smokefree or have identified smokefree dates in the near future. In regions where the enacting of smokefree ordinances has been accomplished, both adult and youth smoking rates have consistently declined. Another propitious factor has been the introduction in 2006 of a new pharmacologic treatment for smoking cessation. Since the majority of smokers want to quit, the primary care physician now has the background of scientific evidence showing the benefits of cessation, the support of national and state "quit lines," increasingly effective modalities of treatment, expanding insurance coverage of pharmacologic agents, and a growing public intolerance to second-hand smoke—all leading to a corresponding increased interest in and motivation for cessation. Assisting a patient in smoking cessation is arguably the most important intervention a physician can make for the patient's long-term health. The physician should be encouraged by the fact that for the first time in U.S. history more Americans today are former smokers than current smokers.
Epidemiology
Tobacco use remains the leading cause of premature death in the United States, contributing to 444,000 deaths annually or 1 in 5 of all deaths.4 Globally the leading causes of death from smoking are cardiovascular disease (1.69 million deaths), cancer (1.4 million deaths), and chronic obstructive pulmonary disease (0.9 million deaths.5 Smoking is responsible for 25-30% of all cases of cancer and approximately 168,000 cancer deaths annually in the United States.6 Tobacco use has been associated with the following malignancies: lung, mouth and pharynx, esophagus, stomach, pancreas, bladder, kidney, breast, cervix, and possibly acute myelogenous leukemia. In regard to lung cancer, tobacco is linked to 90% of cases in males and 78% in females.7 Besides cancer, tobacco use and second-hand smoke have been associated with a host of diseases including heart disease, chronic obstructive lung disease, acute respiratory distress syndrome, stroke, venous thromboembolism, low bone density, gastroesophageal reflux, miscarriage, and sudden infant death syndrome. Approximately 21% of American adults (44.5 million individuals) and 22% of American high school students (3.75 million individuals) smoke.4 Although tobacco consumption has declined from 14 pounds per year in the 1950s to about 5 pounds per year in 2000, it is unlikely that the United States will achieve its Healthy People 2010 objective of reducing smoking prevalence to 12% or less in adults and 16% or less in youth.4
Secondhand Smoking
In June 2006, the Department of Health and Human Services published a comprehensive report entitled "The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General" (can be downloaded at http://www.cdc.gov/tobacco).8 This report updates the health effects of secondhand smoke that result in approximately 50,000 deaths annually in the United States in adults and children who are nonsmokers. Additionally many thousands more suffer morbidity from secondhand smoke, including exacerbations of asthma, respiratory conditions, coronary heart disease, middle ear effusions, etc. The results of this comprehensive report may be influential with smoking patients to induce them to either stop smoking or be more considerate and circumspect in regard to the effect of their secondhand smoke on their families and friends. The report may also be influential with policymakers to convince them to support comprehensive clean indoor air legislation.
Benefits of Cessation
Table 1 highlights the benefits of smoking cessation as identified by the U.S. Surgeon General.9 In addition to these health benefits, there are significant financial implications. Smokers who quit can save as much as $2,500 per year.10 In doing the math, a 40-year-old pack-a-day smoker who quits and puts the savings into a 401(k) retirement fund earning 9% a year will have $250,000 by age 70.11 For society in general, smoking results in productivity losses of $92 billion annually and an additional $75.5 billion in medical expenditures.12 On average, smoking reduces a person's life expectancy by 14 years.
| Table 1. Benefits of Smoking Cessation |
| People who quit regardless of age live longer than people who continue to smoke. Smokers who quit before the age of 50 reduce their risk of dying in half within the next 15 years, compared to those who continue to smoke. Quitting smoking substantially decreases the risk of lung, laryngeal, esophageal, oral, pancreatic, bladder, and cervical cancers. Quitting lowers the risk for other major diseases, including heart disease and stroke. |
Office Interactions
Primary care physicians are in an ideal position to facilitate the identification of smokers and to initiate treatment. Those physicians who see children and youth are best positioned to provide true preventive medicine as most adult smokers who smoke daily began smoking prior to the age of 18. Among daily adult smokers, 90% tried their first cigarette and 70% were daily users at or before the age of 18.13 Genetics and parental influence play a significant role in smoking initiation in children. As the role of peer pressure and the increased sensitivity of the brain receptors play a stronger role in kids, the physician will need to send a strong message to younger patients in terms that they will hopefully understand and act upon. Kids often feel immortal and theoretical risks of future cancer and heart disease are not as influential as the real short-term or visible consequences of smoking such as the out-of-pocket cost and clothes that smell of smoke, as well as perhaps the awareness that they are being duped by seductive advertising to fuel the profit lusts of "Big Tobacco." In the United States, about 60% of current smokers in middle school and high school report one or more quit attempts in the year before being surveyed.14 Unfortunately the U.S. Preventive Services Task Force 2003 Recommendations find limited evidence supporting the effectiveness of screening and counseling of children and adolescents in either preventing initiation or promoting cessation of tobacco use. This limited evidence is due to a lack of clinical studies and not due to research showing strategies to be ineffective. (For more information, visit www.ahrq.gov/clinic/uspstf/uspstbac.htm.)
Nicotine addiction should be viewed as a chronic, relapsing disease. Most adult smokers have considered stopping and most have made at least one attempt to do so. A recent survey has shown that 53% of smokers in the United States tried to quit in the preceding year.13 Seventy percent of smokers visit a physician each year.15 The first step is for the primary care physician to consistently and diligently identify tobacco users. The Joint Commission defines tobacco use as anyone who has smoked within the past 12 months. These patients are at higher risk due to the recidivism known in this time frame. Some physicians may find it easier and perhaps less threatening to patients if the office nurse does the initial personal history intake of smoking history. When multiple personnel (i.e., medical assistant, nurse, doctor) inquire about tobacco use, it sends a strong message about the importance of tobacco use and cessation to the health of patients. Of course, the physician should personally follow up with more detailed questions regarding type, duration, and amount of use as well as clearly communicating to the patient encouragement to quit.
Seventy percent of current smokers want to quit, however, fewer than 7% of smokers who attempt to quit remain smoke-free after one year.16 The average smoker will try to quit 6-9 times in a lifetime.17 Mark Twain said, "Giving up smoking is the easiest thing in the world. I know because I've done it thousands of times." Our job as primary care physicians is to improve on those odds.
Non-pharmacologic Treatment Options
Counseling. In the office setting, the recommended approach is to utilize the 5 As or the perhaps more expedient 3 As and R. (See Tables 2 and 3.) Simply ask all patients if they smoke. Even if a patient has quit within the past 12 months, he or she is at increased risk for relapse, and the physician should inquire about potential triggers during the visit. If the patient currently smokes, the next key component is simply advising the patient to stop smoking. Most patients have thought about quitting or have made efforts in the past. Patients should not be surprised that their doctor would advise them to quit. Although it is probably prudent not to badger patients at every visit, it is important that every visit be an opportunity for the physician or his staff to assess the patient's willingness to quit. This approach can be done in a non-threatening manner, but the patient should be reminded that the doctor is still willing to assist if the patient is ready. If the patient is at a point of contemplation, then the physician should clearly outline that he or she is available to assist the patient in smoking cessation and arrange follow-up. The Legacy Foundation survey reported that surveyed physicians spend 2-10 minutes of an office visit dealing with smoking cessation.3 If that is the only amount of time available to a physician, the best practice might be to refer the patient to appropriate community resources such as telephone quit lines or a tobacco treatment center.
| Table 2. The U.S. Public Health service Clinical Practice Guideline: 5-Step Brief Intervention for Smoking Cessation |
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| Table 3. The 3 As and R | ||||||||
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A systematic review of 17 clinical trials providing episodes of advice and encouragement from a physician increased the rate of smoking cessation from 2-5% over a 6-month period.18 Most primary care physicians are quite busy with their practices, which often do not have staff trained or equipped to deal with intensive counseling or non-pharmacologic intervention such as behavior modification. The physicians should not feel guilty if their practices cannot provide that support. However, they are obligated to know what effective community resources are available to help their patients. Unfortunately, non profit agencies such as the American Lung Association and the American Cancer Society do not have sufficient staff or local resources or programming to provide adequate support. Health maintenance organizations (despite their name) often do not provide group counseling programs or even cover smoking cessation products in their formularies. Local hospitals usually support community wellness programs, but their effectiveness is spotty as wellness is not usually their core competence. Many states are now offering telephone quit lines and even regional tobacco treatment centers. Typically funded by the tobacco settlement law suit money, these resources (if they haven't been squandered or otherwise reappropriated by state legislatures) are designed to provide effective and comprehensive smoking cessation counseling and pharmacologic treatment options.
Nature of Nicotine Addiction
Nicotinic receptors are found throughout the central nervous system. These receptors facilitate the release of multiple neurotransmitters including acetylcholine, norepinephrine, dopamine, serotonin, and beta-endorphins.19 Nicotine is a powerful physiological and psychoactive substance that activates the brain reward system by increasing dopamine release. The brain release mechanism is the final common pathway responsible for many pleasurable experiences, such as sexual activity, eating, and the limbic effects of addictive drugs such as cocaine.
Arterial levels of nicotine are present within 15 seconds of smoking a cigarette, and this rapid absorption is responsible for the nearly immediate gratification found by smokers. Nicotine competitively binds at nicotinic acetylcholine receptors and causes a prolonged activation of these receptors.20 Chronic use of nicotine leads to a desensitized state in which the receptors become unresponsive to agonists and the user experiences diminished pleasure, requiring increasing levels of nicotine to achieve the desired effect.
Nicotine withdrawal symptoms have been well identified and consist typically of several of the following: irritability, craving, insomnia, headache, anxiety, depression, and impaired concentration.21 Nicotine replacement agents mimic the effect of nicotine on the nicotinic receptors but do not duplicate the rapid response associated with smoking a cigarette. Replacement agents, however, do provide a safer alternative to combat the nicotine withdrawal symptoms without the other unpleasant health consequences of smoking such as cancer and heart disease. Because these agents have a slower release resulting in lower blood levels, there is a lower likelihood of addiction.
The combination of cognitive-behavioral therapy and nicotine replacement therapy has been found to be effective and safe in adolescent smokers 13-17 years of age.22
Pharmacologic Treatment Options
A recent review suggests that the best hope of improved treatment outcomes results from combining existing and new pharmacotherapies with effective behavioral therapy.23 Currently there are three categories of FDA-approved smoking cessation pharmacological agents: nicotine replacement products, the antidepressant drug bupropion, and the alpha4beta2 receptor nicotinic acetylcholine partial agonist varenicline (Chantix). Because there is already wide experience with the first two categories, most of the current discussion will focus on the newest agent varenicline and its appropriate use in the primary care setting. Table 4 provides a summary of the key comparisons between the available therapies.
Nicotine Replacement Products. Nicotine replacement therapy (NRT) has been the backbone of smoking cessation efforts. The delivery systems come in the forms of chewing gum, skin patch, nasal spray, oral inhaler, and lozenge. None of these agents delivers nicotine as rapidly as smoking, but they do produce nicotine levels that have been found to be helpful in dulling the nicotine withdrawal symptoms. Because of their wide availability, relatively low cost compared to prescription agents, and low incidence of side-effects, they are often the first line of treatment option. The disadvantages are their modest success rates and the fact that many smokers who come to a physician's office may have already tried these agents and failed and would be understandably reluctant to retry. In this scenario, altering the delivery method from their previous attempt may be an effective strategy.
Bupropion. The use of antidepressants as aids to smoking cessation has been studied, and their expected efficacy seems reasonable. Nicotine may act as an antidepressant, and some smokers become depressed after quitting because quitting unmasks underlying depressive symptoms that already existed.
Although other antidepressants may have efficacy, the sustained-release formulation of bupropion is the only antidepressant approved by the FDA for tobacco use cessation. Bupropion is a relatively weak inhibitor of neuronal uptake of norepinephrine and dopamine, but the mechanism of bupropion's action in enhancing the ability of patients to abstain from smoking is unknown. Bupropion SR (Zyban) appears to work along dopaminergic and noradrenergic pathways to blunt the reward associated with nicotine. Bupropion requires a prescription and has a small but real risk of seizures.
Hurt et al studied 612 subjects who were enrolled in four treatment groups (one placebo, and three with varying doses of bupropion) over a course of 7 weeks.24 The abstinence rate at the end of 12 months was 12.4% for the placebo group and 23.1% for the group who had taken bupropion 150 mg bid during the treatment phase. Although there was a modest weight gain during the treatment phase (in both active and placebo groups), by six months there was no significant difference among the groups for the 59 subjects who remained continuously abstinent. The authors speculated that the efficacy of bupropion may be due to its effect on adrenergic and dopaminergic mechanisms in the brain, rather than on its antidepressant properties. Not all studies, however, demonstrate efficacy. A recent study done in a relatively resistant Veterans Hospital patient population showed no superiority of a brief 7-week course of bupropion over placebo in quit rates at 1 year.25 On the other hand, a rather large study done in a large health care system involving over 1500 patients in which the use of bupropion SR along with mild or moderate counseling resulted in 1-year quit rates of 23.6% to 33.2%.26 Effectiveness will obviously vary depending upon the populations studied.
Bupropion comes as a tablet and a sustained-release or extended-release (long-acting) tablet. The regular tablet (Wellbutrin) is usually taken three or four times per day, with doses at least 6 hours apart. The sustained-release tablet (Wellbutrin SR, Zyban) is usually taken twice per day, with doses at least 8 hours apart. The extended-release tablet (Wellbutrin XL) is usually taken once daily in the morning. The use of these formulations is FDA-approved only for major depression and seasonal affective disorders. It is important to remember that only bupropion SR (Zyban) is approved by the FDA for smoking cessation; this formulation is not FDA-approved to treat depression.
Bupropion SR typically is administered while the patient is still smoking as it takes about one week to reach steady state blood levels. The recommended dosage is one 150 mg pill once a day for the first 3 days. After that, the dosage is increased to one 150 mg pill twice a day, taken 8 hours apart. As bupropion can have a side effect of insomnia, the last dose of the day might be best taken several hours before bedtime. The patient usually is advised to stop smoking after 5-7 days of treatment. Bupropion SR usually is recommended to be taken for 7-12 weeks. If the patient is not successful in quitting by the seventh week, it is unlikely that the patient will quit during this attempt at smoking cessation, and treatment with bupropion should be suspended. Conversely, patients who are successful in quitting should be considered for ongoing therapy. Tapering the dose of bupropion is not necessary when treatment is discontinued. Bupropion is contraindicated in patients with seizure disorders, eating disorders, and those who use monoamine oxidase (MAO) inhibitors. Hypertension requiring treatment has been reported in clinical trials in patients taking bupropion SR, and blood pressure should be monitored.27 As bupropion is a category B drug for pregnancy, it should be considered only if behavioral interventions are unsuccessful.
Varenicline. The newest agent, varenicline (Chantix), received FDA approval in May 2006 via the fast-track review process because of the promise it offered in association with a high level of clinical evidence and low risk of serious side-effects. To date, varenicline arguably has demonstrated the highest level of smoking cessation effectiveness of the currently available FDA-approved agents.
The safety and efficacy of varenicline has been demonstrated in three large, randomized, controlled trials.28-30 The findings from these studies showed that varenicline was four times as effective as placebo and twice as effective as bupropion in smoking cessation.
Mechanism of Action and Pharmacokinetics. Varenicline binds with high affinity and selectivity to alpha4beta2 neuronal acetylcholine receptors. It is believed that varenicline acts as a weak agonist and blocks nicotine's ability to activate alpha4beta2 receptors and thus to stimulate the central nervous mesolimbic dopamine system. This system is thought to provide the underlying reinforcement and reward experienced upon smoking. Varenicline has maximal plasma concentrations within 3-4 hours after administration, and steady-state concentrations are achieved within 4 days.31 It bioavailability is unaffected by food or time of day. Varenicline's half-life is approximately 24 hours and is principally eliminated unchanged in the urine. There are no known pharmacokinetic factors related to age, race, gender, smoking status, or the use of concomitant medications.
Dosage. Varenicline is provided in tablets of 0.5 mg and 1 mg. Dosing should be reduced in the presence of severe renal impairment. It is recommended that the patient set a quit date and start varenicline one week before this date in the following dosage schedule:
Days 1-3: 0.5 mg once daily after eating
Days 4-7: 0.5 mg twice daily after eating
Day 8 – End of treatment 1 mg twice daily after eating
Varenicline should be taken after eating and with a full glass of water. The recommended course of treatment is 12 weeks although an additional course of 12 weeks of treatment can be given at the end of the first 12 weeks to further increase the likelihood of long-term abstinence. Varenicline is supplied in a starting pack, continuing pack and bottles of 56 tablets.
How supplied Description
Packs First month of therapy:
(Pack includes 1 card – 0.5 mg x 11 tablets and 3 cards – 1 mg x 14 tablets)
Continuing months of therapy:
Pack (includes
4 cards – 1 mg x 14 tablets)
Bottles 0.5 mg – bottle of 56
1 mg – bottle of 56
Clinical Outcomes. A randomized, double-blind, parallel-group, placebo- and active-treatment-controlled clinical trial was conducted at 19 U.S. centers.28 One thousand twenty-five smokers were assigned in a 1:1:1 ratio to receive brief counseling and varenicline 1 mg bid, bupropion SR 150 mg bid, or placebo. The primary outcome was continuous 4-week abstinence measured for weeks 9 through 12 using exhaled carbon monoxide monitoring. Varenicline (44.0%) demonstrated statistically significant superior abstinence rates over both placebo (17.7%) and bupropion SR (29.5%) for weeks 9 through 12. Abstinence rates did decline when measured for weeks 9 through 52: 21.9% for varenicline vs. 8.4% for placebo vs. 16.1% for bupropion SR. Participants reported that varenicline reduced craving and withdrawal symptoms, and for those who smoked while receiving the study drug, varenicline reduced smoking satisfaction. The most common side effects were nausea (28.1% for those receiving varenicline) and insomnia (21.9% for those receiving varenicline). Varenicline was found to be safe and well tolerated, with study drug discontinuation similar to those for placebo.
Jorenby et al studied 1413 subjects in a double-blind, placebo-controlled trial at 14 research centers.29 Subjects were randomized to varenicline titrated to 1 mg twice daily or bupropion SR titrated to 150 mg twice daily or placebo for 12 weeks, plus weekly brief smoking cessation counseling. During the last four weeks of treatment, 43.9% of participants on varenicline were continuously abstinent compared with 17.6% in the placebo group and 29.8% in the bupropion SR group. The superiority of varenicline was statistically significant compared to the other two groups. Treatment was discontinued in approximately 10.5% for varenicline, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common side effect with varenicline was nausea, occurring in 29.4% of participants. Despite the nausea, subjects in the varenicline group gained an average of 2.29 kg compared to 1.52 kg in the placebo group and 1.32 kg in the bupropion group.
Tonstad et al conducted a randomized controlled trial involving 1927 cigarette smokers at multiple clinics in 7 countries to study the effect of maintenance therapy with varenicline.30 One thousand two-hundred ten subjects (62.8%) were randomized to additional treatment with varenicline or placebo. In an open-label 12-week study, 64.1% of varenicline-treated subjects were abstinent. In smokers who achieved abstinence for at least 7 days at the end of the 12-week open-label course of varenicline and who continued on varenicline for an additional 12 weeks, varenicline showed superiority over placebo in abstinence rates. This advantage was maintained through the non-treatment follow-up to week 52. Carbon monoxide-confirmed continuous abstinence rate at 52 weeks was 43.6% with varenicline compared to 36.9% with placebo. Varenicline was well tolerated, effective, and safe.
During the open-label phase, adverse events led to treatment discontinuation in 11.9% of participants. About one-fourth of those participants who discontinued did so due to nausea. The median onset to nausea was 8 days and the median duration was 20 days. The incidence of adverse events during the double-blind phase was similar between the varenicline and placebo groups (46% and 45%, respectively).
Adverse Reactions. In the pre-marketing experience with varenicline with more than 4500 subjects, the most common adverse reactions (occurring at rates greater than 5% or twice the rate in placebo-treated patients) were nausea, sleep disturbance, constipation, flatulence, and vomiting.31 For patients taking the maximum recommended dose of 1 mg bid, the incidence of nausea was 30% compared to 10% in patients taking placebo. For patients taking 0.5 mg bid following initial titration, the incidence of nausea was 16% compared to 11% for placebo. For most patients the nausea was mild to moderate and often transient.
Ongoing Support. The manufacturer of varenicline supplies a free "get advice-encouragement-support" program that offers daily activities to manage smoking triggers, gives personalized reports to help track progress, and provides a Cravings Hotline (1-877-CHANTIX or 1-877-242-6849 or www.chantix.com) for those patients having the urge to smoke. Pfizer has also set up a web site that can be used by smokers to help in the cessation process: www.mytimetoquit.com.
A recent study conducted by the Department of Clinical Epidemiology and Biostatistics at McMaster University reviewed the effectiveness of various pharmacological interventions through a systematic review of the literature and meta-analysis.32 Although varenicline seemed to be the most promising agent, Klesges et al address concerns that varenicline's purported greater effectiveness in controlled clinical trials will carry over into the real world of medical practice.33
Special Populations
Hospitalized Patients. A recent National Institutes of Health conference conducted a systematic review of the literature regarding smoking cessation strategies for adults and special populations.34 The review was limited to those studies with six months or greater of follow-up period and minimal sample sizes of 30 patients for randomized, controlled trials and 100 patients for experimental or observational studies. Extrapolation to current practices is tempered by the common limitations to these types of review include varying sample techniques, high refusal or attrition rates, high rates of nonadherence, and lack of consistent adverse event reporting.
Three hospital-based interventional studies were conducted to assess if smoking cessation modalities were effective in the following populations: women admitted to hospital with cardiovascular or peripheral vascular disease; smokers with diabetes; and patients admitted for acute myocardial infarction, unstable angina, or care following coronary artery bypass surgery. All the interventions included nurse counseling, self-help materials, and follow-up contact and were compared to brief advice to quit smoking or related self-help materials. These studies failed to show effective cessation rates in patients hospitalized with tobacco-related clinical diagnoses.
Pregnancy. A study randomly assigning pregnant women and their partners to one of three non-pharmacological interventions showed no significant differences in abstinence rates at any follow-up point between the groups.35 In late pregnancy, more partners were abstinent (15%) compared to 5% in the usual care group (p = 0.02). Previous reviews, however, showed that active counseling interventions did result in significant reduction in continued smoking in late pregnancy.36,37
Heart Disease Patients. Smoking cessation reduces the risk of cardiovascular events, and it would be expected that an exceptionally motivated group of patients would be those admitted to the hospital for myocardial infarction or unstable angina. However, a recent study using a 12-week course of bupropion SR in patients hospitalized for acute cardiovascular disease did not show long-term smoking cessation efficacy over intensive counseling.38
Relapsing Patients. It is well known that nicotine addiction creates a high likelihood for relapse after successful cessation attempts. What is not known is how best to treat these relapsing patients. An interesting study was recently completed in the U.S. Veterans Administration system involving patients who had been prescribed smoking cessation pharmacological therapy in 2002 with either nicotine replacement therapy or bupropion.39 One thousand nine hundred veterans were randomized to one of two groups: one group received a phone call to assess smoking status, quit challenges, and treatment preferences as well as a computerized progress note sent to providers communicating this intervention information while the other group received usual care. The outcomes were studied in 2003. The intervention significantly increased repeat treatment rates and satisfaction with services but did not have a significant effect on abstinence rates. A subsequent analysis of this study showed that almost two-thirds of relapsed smokers were interested in recycling intervention within 30 days with the majority desiring both behavioral and pharmacologic treatment.40 In multivariate analyses, independent predictors of interest in recycling within 30 days included black race, lower smoking level, and greater number of smoking-related health problems.
Table 5 is a list of web sites that can be a practical adjunct and resource for physicians and patients. Table 6 gives a summary of expected success rates among the various treatment options.
| Table 6. Comparison of the Various Pharmacological Interventions |
|
Advocacy Efforts
Assisting patients to stop smoking typically is a laborious one-on-one endeavor. For a wider and more powerful impact, advocacy approaches promise greater scope and effectiveness. There are several ways that concerned physicians can participate in advocacy issues: fostering local and state-wide smokefree initiatives, promoting raising taxes on tobacco products, encouraging health plans and employers to provide coverage for smoking cessation aids, and lobbying legislators to protect kids and adults from tobacco industry advertising and promotion.
Smokefree Initiatives. Secondhand smoke (along with radon and asbestos) has been classified as a Class A carcinogen by the Occupational Safety and Health Administration. The elderly and youth are particularly affected by secondhand smoke. Children exposed to secondhand smoke have increased rates of respiratory disease, middle ear disease, reduced levels of HDL-C, sudden infant death syndrome, and cancer.41 Currently 15 states have smokefree ordinances or laws that restrict smoking in workplaces. (For current list, see Americans for Nonsmokers' Rights web site: www.no-smoke.org.) Ireland in 2004 became the first country to pass a national workplace smoking ban. Effective January 1, 2007, the District of Columbia initiated a smoking ban in force throughout the city's bars and restaurants. Upon taking office as the Speaker of the House in January 2007, Nancy Pelosi officially banned smoking in the Speaker's Lobby. Nancy Pelosi said, "The days of smoke-filled rooms in the United States Capitol are over. Medical science has unquestionably established the dangerous effects of secondhand smoke, including an increased risk of cancer and respiratory diseases. I am a firm believer that Congress should lead by example."42 Creation of smokefree workplaces not only decreases the health risks of involuntary smoking but also leads to a higher rate of smoking cessation among active smokers.43
Should not primary care physicians also lead by example by being vocal and politically active to promote smokefree ordinances that save lives and reduce the economic cost of smoking?
Treaty Ratification. The Framework Convention on Tobacco Control (FCTC) is a legally biding treaty negotiated by the 192 members of the World Health Organization (WHO). The final agreement, reached in May 2003, would encourage countries to:
- Enact comprehensive bans on tobacco advertising, promotion and sponsorship;
- Obligate the placing of rotating health warnings on tobacco products;
- Ban the use of misleading and deceptive terms such as 'light' and 'mild';
- Protect citizens from secondhand smoke;
- Combat smuggling; and
- Increase tobacco taxes.
To date, 168 countries have signed the treaty. The United States signed the treaty in May 2004 but U.S. law requires that all treaties be ratified by the Senate. The treaty has not been brought to the Senate for debate. Each U.S. physician supportive of this treaty has two senators—encourage them to act. (For more information, see www.who.int/tobacco/framework/countrylist/en/index.html.)
Compliance Checks. Under the Synar Amendment, which was enacted in July 1992 as part of the Alcohol, Drug Abuse, and Mental Health Administration Reorganization Act, states must conduct compliance checks and enforce their minimum age-of-sale laws or risk losing block grant funds. All 50 states and the District of Columbia prohibit the sale of tobacco products to minors—most commonly defined as persons under the age of 18. Although these periodic compliance checks to insure that businesses are not illegally selling tobacco products to minors may be performed, unfortunately there are few to no consequences for such activity. Physicians, however, can be advocates for these compliance checks to be sure they are occurring and to promote appropriate media coverage of the results.
Tobacco Taxes. Because price is more influential in minors than in adults, increasing taxes on tobacco products has consistently been associated with decreased tobacco use by minors.44 Only relatively recently have states sought significant increases in tobacco taxes. Until a few years ago Kentucky, which has one of the highest rates of smoking, also had the lowest tobacco tax (3 cents per pack). More than a dozen states are considering higher tobacco taxes this year with the funds targeted to help millions of uninsured people to obtain health insurance.45 Since 2002, 42 states have increased tobacco taxes with an apparent overall corresponding decline in tobacco sales of 15% since 2000 with a steeper fall of 27% in the 19 states and the District of Columbia where cigarette taxes are $1 per pack or more. The increase tax has pushed the average price for a pack of brand-name cigarettes to $4.26, up from $1.96 a decade ago.
Two legitimate uses of taxes are to raise revenue and to positively or negatively influence product consumption. Currently the states with lowest excise taxes are South Carolina ($0.07), Missouri, Mississippi, and Tennessee. States with the highest excise taxes are New Jersey ($2.58), Rhode Island, New York, and Washington. Although tobacco companies will always attempt to counter with retail-level discounting and consumer incentives, physicians should still apply their political influence to appropriately adjust tobacco taxes with the intent to decrease smoking rates in their own communities.
FDA Regulation of Tobacco. In February 2007 a bipartisan Family Smoking Prevention and Tobacco Control Act was simultaneously introduced in the U.S. Senate and House of Representatives.46 This legislation will give the FDA the authority to regulate tobacco products to keep tobacco manufacturers from enticing young people to smoke and to assist current smokers in quitting. Senator Kennedy said, "Congress cannot in good conscience allow the federal agency most responsible for protecting the public health to remain powerless to deal with the enormous risks of tobacco, the most deadly of all consumer products. Health experts believe this legislation is the most important action Congress could take to protect children from this deadly addiction." Congressman Waxman said, "The days of Congress doing the bidding of the tobacco industry are over. This long overdue legislation would give FDA broad powers to regulate tobacco products and protect public health." Congressmen from Kentucky (the country's largest producer of burley tobacco) are, perhaps understandably, not as enthusiastic.47 It is rather ironic that the FDA has jurisdiction over nicotine replacement products but not over tobacco products themselves. Physicians supportive of this legislation will have an opportunity to be politically vocal with their elected officials.
Hope for the Future?
Despite the behavioral modification and pharmacological approaches currently available, treatment of tobacco addiction will remain frustrating and difficult for physicians and patients alike. True breakthrough developments, however, may not be far off. Recent research has identified the insula, a structure the size of a silver dollar, enclosed within the cerebral cortex as a region of the brain linked to emotion and addiction. Research was sparked by the case of a 38-year-old man who abruptly quit his two-pack-a-day habit after suffering a stroke. He lost his urge to smoke virtually overnight and even asked for a room change to get away from another patient who smoked. This man had suffered an insular stroke. A study involving 69 brain-damaged patients showed 19 had affected insulas. Of those 19, 13 had stopped smoking (12 of whom quit instantly with no lingering urges).48 These findings suggest that patients with insular lesions have a greater likelihood of long-term smoking cessation with no relapse and no subsequent urges to smoke. The potential for pharmacological therapy targeted at the insula may have similar results if nicotine addiction can be eliminated while preserving the insula's beneficial functions.
A non-pharmacological approach known as transcranial magnetic stimulation (TMS) may be adapted one day to help smokers quit. TMS involves sending a magnetic current into one side of the brain causing a temporary lesion. At this time these lesions are achievable only in peripheral brain tissue and it is unclear if technology can be adapted to cause deeper lesions where the insula is located. Eichhammer et al treated 14 smokers with rTMS (repetitive transcranial magnetic stimulation) to the left dorsolateral prefrontal cortex.49 Cigarette smoking was significantly reduced (p <.01) in an active stimulation compared with sham stimulation.
At the end of 2003, three companies were working on the development of an anti-nicotine vaccine Xenova (TA-NIC), Nabi (NicVAX), and Cytos (Nicotine-Qbeta).50 The vaccine induces antibodies against the nicotine molecule, intercepting the nicotine en route to its specific receptors. The binding of the antibody to nicotine in turn significantly decreases the nicotine concentration in the brain shortly after smoking. This approach, therefore, interrupts the link between smoking and nicotine-related gratification.
Clonidine and nortriptyline have modest efficacy but side-effects limit their use and they are not FDA-approved. Naltrexone, alprazolam, silver acetate, and lobeline have been used but none has FDA approval for smoking cessation. However, the use of naltrexone (25 mg daily) in conjunction with nicotine replacement therapy produced less weight gain compared with those not taking naltrexone, but there was no change in the quit rate over NRT alone.51 A 100 mg daily dose did increase 6-week quit rates but nausea was a frequent side-effect. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, dopamine receptor D3 antagonists, and inhibitors of nicotine metabolism.52 Of particular interest is rimonabant, the first in a new class of drugs called selective CB1 blockers.19 By inhibiting the CB1 receptors associated with regulating the body's intake of food, reduced dependence on tobacco may be lead to curbing the associated weight-gain often found after smoking cessation.
Summary
At present, physicians have a constellation of aligned stars—increased public awareness of the dangers of smoking and second-hand smoke; legislative momentum for greater regulation and taxation; national support for smoking cessation including free telephone quit lines and governmental agencies such as the CDC for physician and patient education; a newer, safer, and more effective pharmacological treatment modality; and wider coverage by third-party payers for smoking cessation products. Perhaps the only element missing is the resolve of physicians to consistently implement the 3As and R and make a difference in their patients' lives.
References
1. Mackey J, Eriksen M, Shafey O, eds. The Tobacco Atlas, Second Edition. American Cancer Society; 2006: 21.
2. Worldwatch Institute web site. "Cigarette Production Drops." July 7, 2006. Available at www.worldwatch.org/node/4320.
3. Butterfield S. ACP Observer. November 2006:6.
4. National Institutes of Health State-of-the-Science conference statement: Tobacco use: Prevention, cessation, and control. Ann Intern Med 2006;145:839-844.
5. Mackey J, Jemal A, Lee NC, et al, eds. The Cancer Atlas. American Cancer Society, 2006: 30.
6. Cancer Facts & Figures 2007. Atlanta: American Cancer Society; 2007.
7. Surgeon General. The Health Consequences of Smoking: Surgeon General's 2004 Report. Department of Health and Human Services (DHSS). Public Health Service (PHS), Center for Disease Control (CDC), Centre for Chronic Disease Prevention and Health Promotion, Office of Smoking and Health, DHSS Publication No (CDC) 099-7830, 2004.)
8. U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General—Executive Summary. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.
9. US Department of Health and Human Services. The Health Benefits of Smoking Cessation: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion. Office on Smoking and Health; 1990.
10. Singletary M. Smoking poses wealth hazards. The Miami Herald, February 25, 2007, p 3E
11. Smith H. "The High Cost of Smoking." MSN Money Central web site. Available at www.moneycentral.msn.com/content/Insurance/Insureyourhealth/P100291.asp.
12. Centers for Disease Control and Prevention. Annual Smoking-Attributable Mortality, Years of Potential Life Lost and Productivity Losses – United States, 1997-2001. MMWR Morb Mortal Wkly Rep.2005;54(25):625-628.
13. Smoking Cessation. Clinical Practice Guideline Number 18. U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, Centers for Disease Control, AHCPR Publication No. 96-0892; 1996:7
14. Centers for Disease Control and Prevention. Youth tobacco surveillance—United States, 2000. Morb Mortal Wkly Rep 2001;50(SS-4):30.
15. Ockene JK. Smoking intervention: the expanding role of the physician. Am J Public Health 1987 Jul;77(7):782-3.
16. Fiore MC, Bailey WC, Cohen SJ, et al. Clinical Practice Guideline: Treating Tobacco use and Dependence, Rockville, MD: US Dept of Health and Human Services, Public Health Service, 2000.
17. National Institute on Drug Abuse. Research Report Series. Nicotine addiction. NIH Publication No. 01-4342, Preprinted 2001.
18. Law M, Tang JL. An analysis of the effectiveness of interventions intended to help people stop smoking. Arch Intern Med 1995;155:1933-41.
19. Sims TLH. Using pharmacotherapy to treat tobacco dependence in primary care settings. Primary Care Reports 2004:75-86.
20. Watkins SS, Koob GF, Markou A. Nicotine Tob Res 2000 Feb;2(1):19-37.
21. DiFranza JR, Wellman RJ. A sensitization-homeostasis model of nicotine craving, withdrawal, and tolerance: Integrating the clinical and basic science literature. Nicotine Tob Res 2005 ;7(1):9-26.
22. Moolchan ET, Robinson ML, Ernst M, et al. Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction. Pediatrics 2005;115:e407-14.
23. Talwar A, Jain M, Vijayan VK. Pharmacotherapy of tobacco dependence. Med Clin North Am 2004;88:1517-34.
24. Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997;337:1195-1202.
25. Simon JA, Duncan C, Carmody TP, et al. Bupropion for smoking cessation: A randomized trial. Arch Intern Med 2004;164:1797-803.
26. Swan GE, McAfee T, Curry SJ, et al. Effectiveness of bupropion sustained release for smoking cessation in a health care setting: A randomized trial. Arch Intern Med 2003;163:2337-44.
27. Laine C, Goldmann D, eds. In the clinic: Smoking cessation. Ann Intern Med 6 Feb 2007:ITC2-1-16.
28. Gonzales D, Rennard SI, Nides M, et al., Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006;296:47-55.
29. Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006 ;296:56-63.
30. Tonstad S, Tonnesen P, Hajek P, et al, Varenicline Phase 3 Study Group. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006;296:64-71.
31. Chantix (varenicline) Tablets. Full Prescribing Information. Pfizer Labs. LAB 0327-2.0, May 2006.
32. Wu P, Wilson K, Dimoulas P, et al. Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. BMC Public Health. 2006;6:300.
33. Klesges RC, Johnson KC, Somes G. Varenicline for smoking cessation: definite promise, but no panacea. JAMA 2006;296:94-5.
34. Ranney L, Melvin C, Lux L, et al. Systematic Review: Smoking cessation intervention strategies for adults and adults in special populations. Ann Intern Med 2006;145:845-856.
35. McBride CM, Baucom DH, Peterson BL, et al. Prenatal and postpartum smoking abstinence a partner-assisted approach. Am J Prev Med 2004;27:232-238.
36. Lumley J, Oliver SS, Chamberlain C, et al. Interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev 2004;CD001055.
37. Melvin CL, Gaffney C. Treating nicotine use and dependence of pregnant and parenting smokers: An update. Nicotine and Tobacco Research 2004;6S2:S107-S124.
38. Rigotti NA, Thorndike AN, Regan S, et al. Bupropion for smokers hospitalized with acute cardiovascular disease. Am J Med 2006;119:1080-1087.
39. Partin MR, An LC, Nelson DB, et al. Randomized trial of an intervention to facilitate recycling for relapsed smokers. Am J Prev Med 2006;31:293-299. Epub 2006 Aug 22.
40. Fu SS, Partin MR, Snyder A, et al. Promoting repeat tobacco dependence treatment: are relapsed smokers interested? Am J Manag Care 2006;12:235-243.
41. Gold MS, Wang DQ, Bruijnzeel AW. Implications of secondhand smoke in pediatric and adult health. Primary Care Reports 2005:49-60.
42. dcist.com web site. "Smoking Ban Extended to Congress." Available at www.dcist.com/archives/2007/01/10/smoking_ban_ext.php.
43. Bauer JE, Hyland A, Li Q, et al. A longitudinal assessment of the impact of smoke-free worksite policies on tobacco use. Am J Public Health 2005;95:1024-1029.
44. Leverett M, Ashe M, Gerard S, et al. Tobacco use: The impact of prices. J Law Med Ethics 2002;30(3 Suppl):88-95.
45. Wolff R. States consider tobacco tax hikes. USA Today, February 27, 2007, page 1A.
46. "Kennedy, Waxman, Cornyn, and Davis Introduce Tobacco Legislation." Press Release, February 15, 2007. Senator Edward M. Kennedy web site. Available at http://kennedy.senate.gov/newsroom/press_release.cfm?id=30d49497-d37d-4c82-87e1-3b6c9c51e4f1.
47. Patton J. Tobacco control bill filed. Lexington Herald Leader, February 16, 2007: page C7.
48. Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science 2007 Jan 26;315(5811):531-534.
49. Eichhammer P, Johann M, Kharraz A, et al. High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking. J Clin Psychiatry 2003;64:951-953.
50. Cerny T. Anti-nicotine vaccination: Where are we? Recent Results Cancer Res 2005;166:167-175.
51. O'Malley SS, Cooney JL, Krishnan-Sarin S, et al. A controlled trial of naltrexone augmentation of nicotine replacement therapy for smoking cessation. Arch Intern Med 2006;166:667-674.
52. Siu EC, Tyndale RF. Non-nicotinic therapies for smoking cessation. Annu Rev Pharmacol Toxicol 2007;47:541-564.
The escalating consumption of tobacco products is creating an unprecedented worldwide pandemic that in the 21st century will result in 1 billion deaths worldwide.Subscribe Now for Access
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