Using Pharmacotherapy to Treat Tobacco Dependence in Primary Care Settings
Author: Tammy L. H. Sims, MD, MS, Assistant Professor of Pediatrics, Center for Tobacco Research and Intervention, University of Wisconsin Medical School, Madison, WI.
Peer Reviewer: Michael W. Felz, MD, Associate Professor, Department of Family Medicine, Medical College of Georgia, Augusta.
Smoking cessation interventions delivered by primary care physicians are essential in preventing the morbidity and mortality resulting from tobacco use. This article summarizes the major findings of the United States Public Health Service guideline: Treating Tobacco Use and Dependence (USPHS guideline), a comprehensive, evidence-based strategy for treating tobacco dependence. It also provides recommendations for delivering effective clinical interventions to treat tobacco dependence in the primary care setting including behavioral therapies, first-line medications, and second-line medications. The article concludes with updated information about new medications under development. Primary care physicians can implement the strategies recommended by the USPHS guideline to treat their patients by identifying tobacco users, advising them to quit, assessing their willingness to quit, assisting them in quit attempts, and arranging follow-up care for those dependent on tobacco. After reading this article, primary care clinicians will: 1) Understand the rationale for treating tobacco dependence; 2) Recognize why tobacco dependence is a chronic disease; 3) Be familiar with the 5 A’s for providing brief clinical interventions for tobacco users willing to quit; 4) Be familiar with the 5 R’s for motivating tobacco users not yet willing to make a quit attempt; and
5) Know the first-line medications proven to be effective for treating tobacco dependence. Note: This article contains information about an off-label use of nortriptyline and combined nicotine replacement therapies, and information about new drugs in development. —The Editor
Definition of Problem
Tobacco use is the leading cause of preventable morbidity and mortality in the United States. Primary care physicians have an extraordinary opportunity to affect the health of their patients who use tobacco by providing evidence-based interventions to encourage smoking cessation. Approximately 84% of all lung cancer deaths in the United States are attributable to smoking and/or environmental tobacco smoke exposure.1 Furthermore, about 30% of all cancer deaths are caused by smoking.2 In total, cigarette smoking and exposure to environmental tobacco smoke accounts for more than 400,000 deaths annually in the United States.3 Tobacco use is a primary cause of many of the diseases that lead patients to fill primary care offices each day, including angina, coronary artery disease, lung cancer, acute bronchitis, chronic obstructive pulmonary disease (COPD), myocardial infarction (MI), stroke, and asthma. By providing brief counseling and pharmacotherapies effective in treating tobacco dependence, clinicians can increase smoking cessation rates of patients seen in primary care practices.4-6
In 1996, the then Agency for Health Care Policy and Research (now the Agency for Health Care Research and Quality) published clinical practice guidelines for smoking cessation,7 the first comprehensive, evidence-based guideline for the treatment of tobacco addiction in the clinical setting. In 2000, the U.S. Public Health Service published an updated version of the guideline, Treating Tobacco Use and Dependence, that is based on the screening and systematic review of 6,000 journal articles.8 The guideline contains strategies and recommendations to help clinicians, tobacco-dependence treatment specialists, health administrators, and insurers deliver effective, evidence-based interventions to patients dependent on tobacco. This article will focus on USPHS guideline recommendations designed to help primary care clinicians treat their patients who are dependent on tobacco, giving particular attention to the brief clinical interventions and medications that are useful in the primary care setting.
Epidemiology of Tobacco Use
In 2001, the prevalence of smoking among adults 18 and older in the United States was 22.8%; 25.2% of men and 20.7% of women were current smokers.9 While this represents enormous progress since the early 1960s when 44% of all adults smoked, almost 50 million Americans continue to use tobacco regularly.
Age. Most people try their first cigarette and become regular smokers during adolescence.10 Smoking prevalence among adolescents rose dramatically during the 1990s. Though rates have leveled off, more than 20% of high school students continue to smoke.
Gender. Among adult males and females, the prevalence of smoking among men is slightly greater than among women, and men have been consistently heavier smokers than women. Among adolescents in the United States, the prevalence of smoking among males and females is similar.1 Lung cancer now has surpassed breast cancer as the leading cause of cancer death among women.
Ethnicity/Race. In the U.S. adult population, the prevalence of tobacco use is highest among American Indians and Alaska Natives, followed by Caucasians and African-Americans, and lowest among Hispanic Americans and Asian/Pacific Islander Americans.11 In the U.S. adolescent population, based on data from 12th-grade students, the prevalence of tobacco use is highest among American Indians, followed by whites, then Hispanics. African-American teenagers have the lowest prevalence of tobacco use.
Socioeconomic Status. Smoking prevalence is inversely related to level of education, such that those with 16 or more years of education have the lowest smoking rates. Currently, more than 30% of high school dropouts smoke, while only about 12% of college graduates smoke. Also, the prevalence of smoking among blue-collar and service workers is higher than among white-collar workers. Moreover, blue-collar workers are more likely to be heavy smokers. Persons who live below the poverty line are more likely to smoke than those who live at or above the poverty line.1
Basic Neurobiology of Tobacco Dependence
Nicotine is a potent substance with multiple physiological effects, including powerful psychoactive effects.12,13 Nicotinic receptors are distributed throughout the central nervous system. These receptors facilitate the release of different neurotransmitters, including acetylcholine, norepinephrine, dopamine, serotonin, and b-endorphins. Nicotine activates the brain reward system by increasing dopamine release.14 This brain reward system is the common pathway for pleasurable activities (e.g., sexual activity, eating) and for most drugs of addiction.15 Arterial nicotine levels increase markedly—within 15 seconds—after inhaling smoke from a cigarette into the lungs.16 Over time, this rapid delivery of nicotine to the central nervous system leads to tolerance to nicotine, which leads to an increase in cigarette consumption. Between cigarettes, the level of nicotine quickly declines and permits re-sensitization of receptors to the effects of the next cigarette. Individuals tend to smoke more frequently and heavily to obtain the desired effects of nicotine and avoid the unpleasant effects of withdrawal. Nicotine replacement therapy medications are designed to minimize withdrawal symptoms during the quitting process. In contrast to cigarettes and other tobacco products, nicotine replacement therapies have a much slower rate of absorption and delivery of nicotine and do not produce high plasma nicotine levels, which explains their minimal addictive potential.17,18 Also, nicotine replacement therapies supply nicotine in a safe manner, without the other harmful, carcinogenic components contained in tobacco smoke.
Clinical Management
Primary care providers are in an ideal position to help individuals addicted to tobacco. Seventy percent (70%) of smokers visit a physician each year,19 and most report that advice by a clinician is an important motivator in making a quit attempt.20 In fact, a recent survey of smokers in the United States revealed that 52% tried to quit during the preceding year.21 Despite the availability of assistance in the form of medications and behavioral therapy, an estimated 90% of smoking cessation attempts are unassisted (i.e., cold turkey), resulting in low, long-term success rates (3%-5%).22 The first step in providing assistance in the primary care setting is to identify all tobacco users consistently so that clinicians are made aware of the need for intervention.
To achieve this first step, health care systems should be altered to promote the systematic identification of tobacco users during any and all health care visits.8 Once tobacco users are identified, protocols that utilize the 5 A’s (Ask, Advise, Assess, Assist, Arrange) outlined in the USPHS guideline should be used to address this disease properly and provide patients with evidence-based assistance known to improve quitting success rates. Given the chronic nature of tobacco dependence, providers must intervene by advising users to quit, assessing the willingness to quit, assisting users in quitting, and arranging follow-up care. Studies have shown that even brief smoking cessation treatment by health care providers can be effective.5,23-25 Providers are well positioned to advise smokers to quit, provide appropriate interventions (counseling and medication), provide referrals to quitlines or community programs, and arrange follow-up visits to treat this chronic disease.
In addition to counseling, all smokers trying to quit should receive pharmacotherapy except in special circumstances, which include medical contraindications, pregnant/breastfeeding women, adolescent smokers, and those patients who smoke fewer than 10 cigarettes per day. In the presence of any of the above special circumstances, providers must weigh the risks and benefits of medications being considered. Research has shown that the use of nicotine replacement therapy or other pharmacological treatments significantly increase a smoker’s chance of successfully quitting. It is equally important, however, to encourage these smokers to use some form of behavioral counseling (e.g., face-to-face, group, telephone, Internet) along with their pharmacological therapy. Effective strategies for smoking cessation include combined behavioral interventions and pharmacotherapy. With a combination of these interventions, a twofold or more increase in the rate of smoking cessation can be achieved.8
Tobacco addiction is a chronic disease requiring repeated interventions by clinicians who should see each encounter as an opportunity to reach smokers. Most tobacco users attempt cessation five or more times, typically cycling through multiple periods of relapse and remission, before experiencing long-term success.8,26 This information should be used to guide treatment of tobacco dependence, which will involve ongoing chronic care, rather than one-time acute care. Treatment for tobacco dependence should be much like the type of care provided for other chronic diseases (e.g., diabetes and hypertension) and include repetitive, health education-type counseling and advice, as well as necessary adjustments in medication type and/or dose. Relapse should not be viewed as therapeutic failure, nor failure on the part of the patient, but as evidence of the addictiveness of tobacco and the chronic nature of tobacco dependence.
The 5 A’s Model
To reach large numbers of smokers, systems must be in place for the identification and documentation of all smokers. The USPHS guideline recommends the 5 A’s model —Ask, Advise, Assess, Assist, Arrange—for intervening in the primary care setting with patients to identify and treat those using tobacco. These intervention strategies are designed to be brief, requiring three to five minutes to administer.
Ask About Tobacco Use. Ask every patient, at every visit about smoking status and document the information in the medical record. The USPHS guideline recommends that smoking status be included as a vital sign, with chart stickers or with a computerized reminder system. (See Table 1.)
Table 1.
Ask — Systematically Identify All Tobacco Users at Every Visit
Advise to Quit. Once identified, all tobacco users should receive clear, strong, direct, personalized advice to quit using tobacco products. The advice should be clear that quitting—not just cutting down—is best. It should be strong and direct in reference to the burden of diseases caused by or exacerbated by smoking. It should be personalized to the health condition and life circumstances of the individual patient. (See Table 2.)
Table 2.
Advise—Strongly Urge All Tobacco Users to Quit
Assess Willingness to Make a Quit Attempt. Determine the patient’s willingness to make a quit attempt within the next 30-day period. Categorize responses into one of two categories: 1) patients willing to make a quit attempt at this time; and 2) those not willing to make a quit attempt. (See Table 3.)
Table 3.
Assess—Determine Willingness to Make a Quit Attempt
For patients in the first category, provide assistance at that time or refer patient to more intensive assistance if needed. For patients in the second category, provide a brief motivational intervention designed to make them think about the benefits of quitting. (See Table 4.)
Table 4. Enhancing Motivation to Quit Tobacco—the 5 Rs
Assist in the Quit Attempt. Patients who express an interest in quitting should be provided with assistance. (See Table 5.) Encourage patients to set a quit date and to prepare for it by getting rid of all smoking paraphernalia, telling family and friends of their decision, and changing their patterns of smoking leading up to the quit day. Discuss the type of withdrawal symptoms patients can expect once they have quit and the usual time course of those symptoms. Help patients plan how they will handle difficult situations and problems that arise by reviewing any past experiences with quitting and what situations led them to relapse. Provide some additional resources, such as supplemental materials to have at home, the number to a telephone quitline, and or helpful website addresses. Prescribe pharmacotherapy for patients except in special circumstances (i.e., contraindications). (See section on medications.)
Table 5. Assist—Aid the Patient in Quitting
Arrange Follow-up Care. Tobacco dependence is a chronic disease that requires ongoing management and follow-up care after the quit date similar to that required for treating other chronic diseases. Follow-up care can be in person or by telephone. Follow-up care should be timed optimally to help the patient during the first week after a quit attempt (when withdrawal symptoms will be present and risk of relapse is greatest), again within a month, and as needed thereafter. During follow-up sessions congratulate any success, have the patient recommit to abstinence, help them to problem solve, and assess medication effectiveness and or side effects. (See Table 6.)
Table 6. Arrange—Schedule Follow-up Contact
Nonpharmacologic Behavioral Therapy (Individual, Group, or Proactive Telephone Counseling)
Ideal treatment for tobacco dependence includes behavioral therapy in addition to pharmacotherapy. Behavioral therapy in conjunction with medications has yielded quit rates of 30-40% at one-year follow-up, compared with medication-alone quit rates that reach 15-25%.8 Behavioral interventions can be delivered in a variety of settings, which have been proven effective in smoking cessation interventions, including individual counseling, group counseling and proactive telephone counseling. These counseling interventions should provide patients with three essential elements to increase their chances of successful abstinence: 1) problem-solving skills training; 2) social support as part of treatment; and 3) help locating and securing social support outside of treatment. Clinicians can help their patients think about and identify situations that increase their risk of relapsing back to smoking, and develop stress management and coping strategies that will help them resist urges and maintain abstinence. Providing basic information about expected withdrawal symptoms and their time course will better prepare patients for success. Clinicians and counselors can provide social support during treatment by expressing concern and allowing open dialogue about the quitting process. Clinicians also can help patients identify and arrange additional social support in their environment (e.g., friends, co-workers and family members), and from trained professionals (e.g., quitline counselors).
Pharmacotherapy—First-Line Medications
Bupropion Sustained Release (Bupropion SR). Bupropion SR is available by prescription only and is the only non-nicotine medication approved by the U.S. Food and Drug Administration (FDA) for smoking-cessation treatment. It is marketed as Zyban for smoking cessation or Wellbutrin for depression. Bupropion has been shown to be effective for smoking cessation and well tolerated in a number of studies.27-29 It is contraindicated in individuals with seizure disorders, eating disorders, or who used monoamine oxidase (MAO) inhibitors within the previous two weeks. The USPHS guideline recommends it as first-line pharmacotherapy for smoking cessation, and it is the only non-nicotine medication so designated. (See Table 7.)
Nicotine Replacement Therapies (NRTs). NRT products are available in various forms. The active ingredient in such products is nicotine. There is no evidence of increased cardiovascular risk with NRT.8 The use of NRTs is contraindicated medically in cases of MI (within previous two weeks), serious arrhythmia, serious or worsening angina pectoris, and accelerated hypertension.
Nicotine Gum. Nicotine gum is available over the counter in 2-mg and 4-mg doses. It is absorbed best in a basic environment, and users should be advised to "park and chew" to achieve maximum absorption. The dosage recommendation is to chew one piece every 1 to 2 hours for weeks 1 to 6, one piece every 2 to 4 hours for weeks 7 to 9, and one piece every 4 to 8 hours for weeks 10 to 12. The maximum dosage is 24 pieces per day. The recommended duration of treatment is 12 weeks.30
Nicotine Inhaler. Nicotine inhalers are available by prescription only. The recommended dosage of nicotine inhalers is 6-16 cartridges per day (each contains 10 mg of nicotine). The recommended duration of treatment is 12 weeks followed by a 6- to 12-week period of weaning. Therefore, six months is the maximum recommended length of therapy.30
Nicotine Lozenge. The new nicotine lozenge has been shown to have low abuse liability, not greater than the nicotine gum.31 It is available in 2-mg and 4-mg doses and should be allowed to dissolve in the mouth without chewing or swallowing. Individuals who typically smoke their first cigarette within 30 minutes of awakening should use the 4-mg dose. Because it dissolves completely, it delivers 25-27% more nicotine than the nicotine gum. In clinical trials, it increased quit rates two-fold compared with placebo, reduced cravings and withdrawal symptoms, and temporarily suppressed weight gain.32
Nicotine Nasal Spray. Nicotine nasal spray is available by prescription only. Each 10-mL spray bottle contains 100 mg of nicotine (10 mg/mL). One dose of nicotine nasal spray (two sprays, one in each nostril) contains approximately 1 mg of nicotine. The recommendation is one to two doses per hour, which may be increased to a maximum of 40 doses per day for three months, followed by tapering of the daily dose. The recommended minimum dosage is eight doses per day, and the recommended duration of treatment is up to six months.30
Nicotine Patch. Nicotine patches are available both over the counter (OTC) and by prescription. The recommended OTC and prescription nicotine patch dosage is 21 mg/day for weeks 1 to 6, tapered to 14mg/day for weeks 7 and 8, and then tapered to 7 mg/day for weeks 9 and 10. Those smoking fewer than 10 cigarettes per day are advised to start at 14 mg/day instead of 21 mg/day. The recommended duration of treatment with nicotine patches is 8 to 10 weeks. Nicotine patches are available for 24-hour or 16-hour use.30
Pharmacotherapy—Second-line Medications
Based upon findings from the USPHS guideline panel, two medications were listed as second-line pharmacotherapies to be considered if first-line pharmacotherapies are not effective or are contraindicated.
Clonidine. Clonidine is an anti-hypertensive that has been shown in clinical trials to double quit rates compared with placebo. However, it has not been approved by the FDA for smoking cessation, nor has a specific dosing regimen been established. For these and other reasons (i.e., the side effect profile, a warning regarding abrupt discontinuation), it was recommended as a second-line agent by the guideline panel. Clinicians might consider using clonidine for patients with contraindications to using first-line medications or for patients who are unable to quit using first-line medications, but should be aware of the side effect profile and specific precautions and warnings regarding its use.
Nortriptyline. Nortriptyline is an anti-depressant that has been shown in a limited number of clinical trials to more than double quit rates compared with placebos. However, it has not been approved by the FDA for smoking cessation. The USPHS guideline panel recommended it as a second-line agent because of the limited number of studies, the lack of FDA approval for smoking cessation, and because of its side effect profile. Clinicians might consider using nortriptyline for patients who have contraindications to first-line medications or who were unable to quit smoking by using them. Clinicians should be aware of specific warnings and the side effect profile of this medication.
Multiple Therapies. Though combined NRT is not FDA approved currently, a number of studies have proven that combination therapy results in increased quit rates, and such combinations are recommended in the USPHS guideline. In addition, bupropion SR may be combined with any of the NRTs. In patients unable to quit using single therapy, combination therapy may be considered. Nicotine patch plus gum33,34 or nicotine patch plus nasal spray35 are more effective in promoting smoking cessation than a single NRT.
See Table 8, Clinical Guidelines for Prescribing Pharmacotherapy for Smoking Cessation.
When to Refer to a Specialist
Despite health warnings and advice from physicians, a subgroup of smokers never quit. Difficulty quitting tobacco use has been associated with a number of characteristics, including a high level of nicotine dependence,36 comorbid psychopathology,37,38 and lower socio-economic status.39 If one of these characteristics exists, referral to smoking-cessation specialists should be considered. A high level of nicotine dependence might be predicted by one of the following conditions: smoking more than 20 cigarettes per day; smoking within 30 minutes of awakening; finding it difficult to not smoke in situations and places where smoking is prohibited; and scoring within the high range on tests of nicotine dependence, such as the Fagerstrom Tolerance Questionnaire. Comorbid psychiatric problems—especially alcohol abuse and depression—might result in poor medication compliance. Almost 20% of heavy smokers have current alcohol problems40 and nearly 40% of current smokers have a history of depression.38,41 Persons who live below the poverty line (lower socio-economic status) are more likely to smoke than those who live at or above the poverty line.1 Also, lower socio-economic status is associated with less access to cessation services, more environmental stressors, and exposure to other smokers in the social and work environment.
Special Challenges, Controversies, Pitfalls, Areas in Need of Research
Symptoms and Time Course of Withdrawal as Relates to Pharmacotherapy. While nicotine withdrawal symptoms vary from individual to individual, symptoms usually involve unpleasant effects, such as anxiety, irritability, difficulty concentrating, restlessness, impatience, hunger, tremor, racing heart, sweating, dizziness, nicotine craving, insomnia, drowsiness, headaches, digestive disturbances, and depression.42 Withdrawal symptoms typically increase during the first week following abstinence, then steadily improve during the next four weeks. However, smoking withdrawal is variable among individual smokers, and some individuals experience symptoms that do not improve steadily, but instead either gradually improve or show very little improvement during the typical time course.43 Individuals who experience withdrawal symptoms that increase or remain elevated during an extended period of time are at higher risk for relapse than those who have symptoms that steadily decline.43,44 Such individuals should be considered for prolonged therapy and allowed to use NRT beyond the recommended time period to help prevent relapse to smoking.
Duration of Therapy. There is no consensus among experts about the optimum duration of pharmacotherapy for treating tobacco dependence. The recommendations regarding duration of therapy with nicotine replacement medications and bupropion as outlined in the Physicians’ Desk Reference (PDR)30 are based upon trials designed to determine effectiveness and safety of the medications, not necessarily maximum efficacy. Long-term use of pharmacotherapy (i.e., use beyond the recommended time period) might be an effective strategy for preventing relapse. For example, there is some evidence to suggest that though seven weeks of bupropion SR is effective for smoking cessation, a longer duration of treatment might prolong abstinence or time to relapse.45
Relapse Prevention (Risk Factors for Relapse). Most relapses occur early in the quitting process. Primary care physicians should engage in relapse prevention with all former smokers because patients are at risk for relapse months, and even years, after the quit date. Relapse prevention is very important soon after quitting—especially within the first three months—and can be delivered by follow-up clinical visits, follow-up telephone counseling, or using proactive tobacco quitlines. Issues that should be discussed in an effort to prevent relapse include the benefits of cessation, any successes, and any problems encountered that threaten continued abstinence. Patients should be encouraged to seek help and to report promptly any difficulties (e.g., depression, medication side effects, strong withdrawal symptoms, or lack of social support). For patients at risk for relapse, consider a prolonged course of pharmacotherapy, beyond that recommended in the PDR.46
Special Populations (Gender, Adolescents, Pregnant Women, Race/Ethnic Minorities). Though research has demonstrated gender differences in smoking and cessation behavior, the USPHS guideline states that the same smoking-cessation interventions are effective for men and women and should be made available without regard to gender. Most smokers begin daily smoking as teenagers, before age 18. Many adolescent smokers report symptoms of nicotine dependence and experience withdrawal symptoms when trying to quit. Since nicotine replacement therapy is far safer than smoking, it should be considered for all smokers who need help quitting, including teens. Smoking during pregnancy is associated with serious risks to the pregnant smoker and the fetus. Although abstinence early in pregnancy will produce the greatest benefits, abstinence at any point during pregnancy is beneficial. Therefore, clinicians should offer effective smoking-cessation interventions to pregnant smokers at any and all prenatal visits. The USPHS guideline recommends that pharmacotherapy be considered when the likelihood of quitting—with its benefits for the expectant mother and fetus—outweighs the risks of the medication and continued smoking. Smoking-cessation treatments have been shown to be effective for various racial and ethnic minorities. Therefore, smokers from different racial/ethnic backgrounds should be offered effective interventions that are culturally relevant and appropriate.
Chronic Nature of Addiction. Tobacco dependence is a chronic disease associated with periods of abstinence and relapse that will require repeated systematic interventions. Studies have shown that it takes the average smoker four to five quit attempts before achieving smoking-cessation success.26 Indeed, a significant number of former smokers have difficulty maintaining abstinence and relapse back to smoking even after use of pharmacotherapy. In the first year following cessation, relapse rates of 80% have been reported.47,48 Therefore, physicians should think of tobacco dependence as a chronic disease to be managed similar to other chronic diseases—with ongoing rather than simply acute care. Factors that contribute to failed quit attempts should be addressed, and the patient should be encouraged to make another quit attempt as soon as possible. Some factors to consider are patient motivation, co-morbidities, stress, availability of social support, and use of medications.
New Medications—Approved for Use
Nicotine Lozenge. Nicotine lozenge might be a more acceptable form of oral nicotine replacement therapy than nicotine gum for patients who have difficulty chewing and parking the gum correctly. In a double-blind, placebo-controlled, randomized clinical trial, the nicotine lozenge was found to be safe and effective for smoking cessation in low-and high-dependence smokers. The 2-mg lozenge had 2.1 greater odds, and the 4-mg lozenge had 3.7 greater odds of producing abstinence at six weeks compared with placebo. Significant treatment effects were maintained for a full year. The adverse events reported during use were moderate and comparable with those seen with nicotine gum.32
New Medications Under Development
NicVaxä. NicVaxä is being tested in clinical trials by Nabi Biopharmaceuticals as a novel drug approach to help curb the cravings for cigarettes. Given intramuscularly, the vaccine is designed to trigger the immune system to make antibodies that attach to nicotine molecules. This vaccine-antibody complex is too large to cross the blood-brain barrier, thereby, blocking or hindering the effect of nicotine on the body. Preliminary animal studies have shown that the nicotine-specific antibodies produced by NicVaxä also reduced the effects of nicotine on the heart and on blood pressure.49
Rimonabant. Rimonabant is the first in a new class of drugs called selective CB1 blockers. The drug works by inhibiting the CB1 receptor, one of two receptors found in the endocannabinoid system (EC system), that are located in the brain and in other parts of the body. Associated with systems regulating the body’s intake of food, the EC system also is involved in tobacco dependency. Chronic tobacco use over-stimulates the EC system creating an imbalance. By blocking the CB1 receptor, rimonabant helps restore balance to the EC system, resulting in reduced dependence on tobacco. Rimonabant, which is under development by Sanofi-Synthelabo, represents a potentially promising new treatment option that can help people stop smoking while curbing post-cessation weight gain.50
Varenicline. Varenicline is a new kind of medication being tested by Pfizer, Inc. for smoking cessation. It has the potential to ease cravings and withdrawal symptoms without being pleasurable or addictive. It works by attaching to the nicotine receptors in the brain and letting the brain think that nicotine is attached so individuals do not experience the unpleasant symptoms of nicotine withdrawal. Also, if a former smoker lapses and smokes a cigarette, the drug has the potential to reduce the sense of satisfaction associated with smoking.51,52
Conclusions
In conclusion, tobacco use remains the leading cause of preventable morbidity and mortality in the United States. Tobacco dependence is and should be treated as a chronic disease that requires systematic, ongoing management. Effective, evidence-based strategies exist for treating this costly disease, including pharmacotherapies and behavioral therapies. Also, new and better therapies are under development.
Primary care providers are well positioned to intervene with tobacco users by implementing the strategies recommended by the USPHS guideline to provide effective clinical interventions.
References
1. Giovino GA. Epidemiology of tobacco use in the United States. Oncogene 2002;21:7326-7340.
2. Doll R, Peto R. The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 1981;66:1191-1308.
3. Centers for Disease Control and Prevention. Annual smoking-attributable mortality, years of potential life lost, and economic costs—United States, 1995-1999. MMWR 2002;51:300-303.
4. Fiore MC, Smith SS, Jorenby DE, et al. The effectiveness of the nicotine patch for smoking cessation: A meta-analysis. JAMA 1994;271:1940-1947.
5. Russell MAH, Wilson C, Taylor C, et al. Effect of general practitioners’ advice against smoking. BMJ 1979;2:231-235.
6. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. Alexandria, Virginia: International Medical Publishing; 1996.
7. Fiore MC, Bailey WC, Cohen SJ, et al. Smoking cessation. Clinical Practice Guideline No 18. Rockville, Maryland: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research,1996. (AHCPR Publication No 96-0692.)
8. Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services Public Health Service; 2000.
9. Centers for Disease Control and Prevention. Cigarette smoking among adults—United States, 2001. MMWR 2003;52:953-956.
10. U.S. Department of Health and Human Services. Preventing Tobacco Use Among Young People: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health;1994.
11. Centers for Disease Control and Prevention. Cigarette Smoking Among Adults-United States, 1999. MMWR 2001;50:869-873.
12. Benowitz NLPharmacology of nicotine: Addiction and therapeutics. Annu Rev Pharmacol Toxicol 1996;35:597-613.
13. Henningfield JE, Cohen C, Pickworth WB. Psychopharmacology of nicotine. In: Orleans CT, et al, eds. Nicotine addiction: Principles and Management. New York:Oxford University Press;1993:24-45.
14. Zhuo FM, Liang Y, Dani JA. Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum. Nat Neurosci 2001;4:1224-1229.
15. Tomkins DM, Sellers EM. Addiction and the brain: The role of neurotransmitters in the cause and treatment of drug dependence. CMAJ 2001;164:817-821.
16. Stauffer HP, Riedwyl H. Interaction and pH dependence of effects of nicotine and carbon monoxide in cigarette smoke inhalation experiments with rats. Agents Actions 1977;7:579-588.
17. West R, Hajek P, Foulds J, et al. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl) 2000;149:198-202.
18. Henningfield JE, Keenan RM. Nicotine delivery kinetics and abuse liability. J Consult Clin Psychol 1993;61:743-750.
19. Ockene JK. Smoking intervention: The expanding role of the physician. Am J Public Health 1987;7:782-783
20. Herin K. Smoking cessation: The physician’s role. Postgrad Med 1982;71:99-106.
21. Centers for Disease Control and Prevention. State-specific prevalence of current cigarette smoking among adults United States, 2002. MMWR 2004;52:1277-1280.
22. U.S. Department of Health and Human Services. The Health Benefits of Smoking Cessation: A report of the Surgeon General. Atlanta: U.S Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health;1990. DHHS Publication No. 90-8416.
23. Fiore MC, Jorenby DE, Schensky AE, et al. Smoking status as the new vital sign: Effect on assessment and intervention in patients who smoke. Mayo Clin Proc 1995;70:209-213.
24. Glynn TJ, Manley MW, Pechacek TF. Physician-initiated smoking cessation program: The National Cancer Institute trials. Prog Clin Biol Res 1990;339:11-25.
25. Jaen C, Stange K, Tumiel L, et al. Missed opportunities for prevention: Smoking cessation advice and the competing demands of practice. J Fam Pract 1997;45:348-354.
26. U.S. Department of Health and Human Services. The Health Consequences of Smoking: Nicotine Addiction: A Report of the Surgeon General. Rockville, MD: U.S. Public Health Service;1988.
27. Hurt RD, Sachs DPL, Glover ED et al. A comparison of sustained-release bupropion SR and placebo for smoking cessation. N Engl J Med 1997;337:1195-1202.
28. Jorenby DE, Leishow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-691.
29. Hays JT, Hurt RD, Rigotti NA et al. Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation: A randomized controlled trial. Ann Intern Med 2001;135:423-433.
30. Physicians’ Desk Reference. 58 ed. Montvale, NJ; Thomson:2004: 1697-1701.
31. Houtsmuller EJ, Henningfield JE, Stitzer ML. Subjective effect of the nicotine lozenge: Assessment of abuse liability. Psychopharmacology 2003;167:20-27.
32. Shiffman S, Dresler CM, Hajek P, et al. Efficacy of nicotine lozenge for smoking cessation. Arch Intern Med 2002;162:1267-1276.
33. Kornitzer M, Boutsen M, Dramaix, et al. Combined use of nicotine patch and gum in smoking cessation: A placebo-controlled clinical trial. Prev Med 1995;24:41-47.
34. Puska P, Korhonen H, Vartiainen E, et al. Combined use of nicotine patch and gum compared with gum alone in smoking cessation: A clinical trial in North Karelia. Tob Control 1995;4:231-235.
35. Blondal T, Gudmundsson LJ, Olafsdottir I, et al. Nicotine nasal spray with nicotine patch for smoking cessation: Randomized trial with six-year follow-up. BMJ 1999;318:285-288.
36. Colby SM, Tiffany ST, Shiffman S, et al. Measuring nicotine dependence among youth: A review of available approaches and instruments. Drug Alcohol Depend. 2000;59:S23-S39.
37. Hughes JR. The evidence for hardening. In: National Cancer Institute ed. Those Who Continue to Smoke: Is Achieving Abstinence Harder and Do We Need to Change Our Intervention? (Smoking and Tobacco Control Monograph No. 15). Bethesda, MD: U.S. Public Health Service, National Cancer Institute. (NIH Publication No. 03-5370).
38. Glassman AH. Cigarette smoking: Implications for psychiatric illness. Amer J Psych 1993;150:546-553.
39. Trosclair A, Husten C, Pederson L, et al. Cigarette smoking among adults-United States, 2000. MMWR 2002;51:642-645.
40. Hughes JR. Smoking and alcoholism. In Hatsukami DK, Cox J, eds. Behavioral Approaches to Addiction. New York: Calmers; 1994:1-3.
41. Hall SM, Munoz RF, Reus VI, et al. Nicotine, negative affect, and depression. J Consult Clin Psychol 1993;61:761-767.
42. Brigham J, Henningfield JE, Stitzer ML. Smoking relapse: A review. Int J Addict 1991;25:1239-1255.
43. Piasecki TM, Fiore MC, Baker TB. Profiles in discouragement: Two studies of variability in the time course of smoking withdrawal symptoms. J Abnorm Psychol 1998;107:238-251.
44. Piasecki TM, Niaura R, Shadel WG, et al. Smoking withdrawal dynamics in unaided quitters. J Abnorm Psychol 2000;109:74-86.
45. Tonnesen P, Tonstad S, Hjalmarson A, et al. A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation. J Intern Med 2003;254:184-192.
46. Sims TH, Fiore MC. Pharmacotherapy for treating tobacco dependence: What is the ideal duration of therapy? CNS Drugs 2002; 16:653-662.
47. Lichenstein E, Glasgow RE, Abrams DB. Social support in smoking cessations: In search of effective interventions. Behav Ther 1986;17:607-619.
48. Murray RP, Voelker HT, Rakos RF, et al. Intervention for relapse to smoking: The Lung Health Study restart programs. Addict Behav 1997;22:281-286.
49. Nabi Pharmaceuticals. Key Facts About Nicotine Addiction and NicVAX. Available at: www.nabi.com/pdf/pipe_nicotine_nicvax.pdf. Accessed May 13, 2004.
50. SearchFN.com resources page. Rimonabant helps smokers quit while limiting post cessation weight gain. Researchers at University of Cincinnati College of Medicine present results of the STRATUS-US trial at American College of Cardiology meeting. Available at: www.searchfn.com/rimonabant.html. Accessed April 16, 2004.
51. Roan, S. Another weapon against the addiction. Drug under study could help more smokers stop. [Los Angeles Times, November 18, 2003.] Available at: www.post-gazette.com/pg/03322/240830.stm. Accessed May 5, 2004.
52. Research Matters at Harvard University resources page. New drug may give smokers promising new option for kicking habit. Available at: www.researchmatters.harvard.edu/story.php?article_id=693. Accessed May 5, 2004.
This article summarizes the major findings of the United States Public Health Service guideline: Treating Tobacco Use and Dependence, a comprehensive, evidence-based strategy for treating tobacco dependence. It also provides recommendations for delivering effective clinical interventions to treat tobacco dependence in the primary care setting including behavioral therapies, first-line medications, and second-line medications. The article concludes with updated information about new medications under development.
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