the patient, smoking, smoking cessation, nicotine replacement, nicotine patch, nicotine dependence, nicotine withdrawal, preparation stage, AMERICAN FAMILY PHYSICIAN, Nicotrol Inhaler, percent, common side effects, relapse, precontemplation, nicotine gum, Public Health Service, behavioral support, clinical practice guideline, transtheoretical model, Agency for Health Care Policy and Research, American Society of Addiction Medicine, Rustin TA, addictive behaviors, N Engl J Med, smoking in the United States, addictive behavior, J Drug Educ, Centers for Disease Control and Prevention, transdermal nicotine, Pharmacologic treatment, U.S. Dept. of Health and Human Services, Bupropion, nicotine inhaler, Combination therapy, consequences of smoking, Medical University of South Carolina, smoking rates, throat irritation, cigarette smoking, Maintenance stage, positive reinforcement, patch application, Nicotine Nasal Spray
COVER ARTICLE PRACTICAL THERAPEUTICS
Smoking Cessation: Integration of Behavioral and Drug Therapies ROBERT MALLIN, M.D., Medical University of South Carolina
, Charleston, South Carolina Family physicians should take advantage of each contact with smokers to encourage and support smoking cessation. Once a patient is identified as a smoker, tools are available to assess readiness for change. Using MOTIVATIONAL INTERVIEWING
techniques, the physician can help the patient move from the precontemplation stage through the contemplation stage to the preparation stage, where plans are made for the initiation of nicotine replacement and/or bupropion therapy when indicated. Continued motivational techniques and support are needed in the action stage, when the patient stops smoking. Group or individual behavioral counseling can facilitate smoking cessation and improve quit rates. Combined use of behavioral and drug therapies can dramatically improve the patient's chance of quitting smoking. A plan should be in place for recycling the patient through the appropriate stages if relapse should occur. (Am Fam Physician 2002;65:1107-14,1117. Copyright© 2002 American Academy
of Family Physicians.)
O A patient informa- tion handout on how to stop smoking, written by the author of this article, is provided on page 1117.
Members of various Family Practice
departments develop articles for "Practical Therapeutics." This article is one in a series coordinated by the Department of Family Medicine at the Medical University of South Carolina. Guest editor of the series is William J. Hueston, M.D.
Despite increased research on smoking, heightened awareness of the consequences of smoking, and considerable publicity about litigation against tobacco companies, statistics published within the past five years indicate that 23.5 percent of adults in the United States continue to smoke.1 Even more alarming is the increase in smoking among persons 18 to 24 years of age, almost 33 percent of whom currently use tobacco. In this age group, smoking rates increased by 32 percent between 1991 and 1997.2 Although 70 percent of patients who smoke say they would like to quit, only 7.9 percent are able to do so without help.3 The advice of a physician alone can improve the smoking cessation rate to 10.2 percent.4 The combined use of nicotine replacement, bupropion (Zyban), and social or behavioral support can increase the quit rate to 35 percent.5 Smoking cessation treatment is effective and should be offered to smokers at every office or clinic visit. This article outlines a practical approach that can increase the likelihood of successful smoking cessation.
Identification of the Smoker and Assessment of Readiness to Quit It is important to add a question about smoking to the questions routinely asked while a patient's vital signs are being taken. Physicians have been shown to be three times more likely to intervene when they know that a patient smokes.6 Further assessment using a modified CAGE questionnaire (Table 1)7 or an abbreviated form of the Fagerstrцm test (Figure 1)8,9 can provide information about whether a patient is addicted to or physically dependent on nicotine.10 Once the diagnosis of nicotine dependence is made, the next step is to assess the patient's readiness to change. The fivestage transtheoretical model for readiness to change can be applied to addictive behaviors such as smoking.11 The five stages in this model are precontemplation, contemplation, preparation, action, and maintenance. In the precontemplation stage, a patient does not believe that smoking is a problem or refuses to consider smoking cessation. In the contemplation stage, the patient recognizes that smoking is a problem and wants to stop. During the
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Only 7.9 percent of smokers are able to quit without help. The combined use of nicotine replacement, social or behavioral support, and bupropion can increase the quit rate to 35 percent. preparation stage, the patient makes specific plans to stop smoking, such as setting a quit date and determining how smoking cessation will be accomplished. In the action stage, the patient stops smoking. Finally, the maintenance stage is marked by the patient's continued abstinence from smoking. Relapse to smoking behavior is common. Patients often cycle through the stages of change
several times before reaching stable abstinence.11 Motivational Interviewing PRECONTEMPLATION STAGE To select the most appropriate interventions, the family physician needs to know the patient's present readiness to change. Offering a prescription for nicotine replacement to a patient who is in the precontemplation stage is unlikely to be successful, because doing so essentially asks the patient to move from precontemplation to action without going through the necessary intervening stages. Rather, the physician should encour- TABLE 1 CAGE Questionnaire for Smoking* 1. Have you ever tried to, or felt the need to, Cut down on your smoking? 2. Do you ever get Annoyed when people tell you to quit smoking? 3. Do you ever feel Guilty about smoking? 4. Do you ever smoke within one-half hour of waking up (Eye-opener)? *--Two "yes" responses constitute a positive screening test. Adapted with permission from Lairson DR, Harrist R, Martin DW, Ramby R, Rustin TA, Swint JM, et al. Screening for patients with alcohol problems
: severity of patients identified by the CAGE. J Drug Educ 1992;22:337-52.
age the patient in the precontemplation stage to think about his or her smoking and to consider the possibility that smoking is a problem that needs attention. Brief interventions can be effective in the precontemplation stage and as the patient moves from one stage to the next.12 Effective interventions include the following: 1. Educate the patient about the effects of smoking. 2. Recommend changes in behavior. 3. List options for achieving behavioral change
. 4. Discuss the patient's reactions to the physician's feedback and recommendations. 5. Follow up to monitor and reinforce behavioral change. This process, known as "motivational interviewing," uses empathy rather than confrontation. It acknowledges that the patient, not the physician, is responsible for changing behavior.13 CONTEMPLATION STAGE If further discussion on the return visit reveals that the patient now agrees that smoking is a problem and would like to consider quitting, the patient has entered the contemplation stage. Interventions to consider at this stage include providing further education about the effects of smoking and encouraging the patient to consider the positive aspects of not smoking, such as improved health, a more positive self image, and economic savings. PREPARATION STAGE Once the patient agrees that the benefits of not smoking outweigh the pleasure derived from smoking and has decided to quit, he or she has entered the preparation stage. At this point, it is appropriate to discuss various nicotine replacement systems, the possible use of bupropion, and the need for social and Family Support
. The physician should also help the patient develop a clear plan for smoking cessation.
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Tasks for the patient and physician during the preparation stage may include the following10: 1. Setting a definite quit date. Often, a meaningful date, such as a birthday or anniversary, provides the patient with increased motivation. 2. Gathering support for smoking cessation. The patient should let family members
and other significant persons know that he or she has decided to quit smoking on a certain date, and should ask those individuals for help. The physician might encourage the patient to take part in a support group or a community or agency program that focuses on smoking cessation. 3. Preparing the environment. The patient should be counseled to remove cigarettes, ashtrays, and other smoking-related paraphernalia from his or her home, car, and office. The patient should ask others not to smoke in his or her presence. 4. Formulating plans to avoid triggers. When prompted, many patients can identify images, rituals, sensory experiences, and emotional rewards that they associate with smoking. The physician and patient can begin to discuss healthy substitution behaviors that might help prevent relapse. Counseling patients to avoid alcohol is a good strategy because drinking lowers inhibitions, thereby reducing the chance of successful smoking cessation. 5. Selecting a nicotine replacement system, if needed. 6. Initiating bupropion, if needed. If bupropion is part of the smoking cessation plan, treatment should be initiated one to two weeks before the quit date. ACTION AND MAINTENANCE STAGES The action stage begins on the quit date. By this date, bupropion should have been started (if used), the nicotine replacement system of choice should be on hand (if used), and the patient's environment should have been cleared of smoking-related materials. During the action stage, behavioral support through self-help or professionally run group
Once a patient is in the preparation stage for quitting smoking, it is appropriate to discuss specific smoking cessation methods. meetings, frequent office visits, and/or telephone calls from support personnel can enhance the effectiveness of the cessation attempt.14 The purpose of these contacts should be to support continued smoking cessation in the recently abstinent smoker. These contacts should be made at least weekly in the first month, and again when the patients stops nicotine replacement and bupropion therapy. It is important for the patient to report perceived benefits from having stopped smoking, side effects
of medications, and current or anticipated difficulty in maintaining absti- Brief Fagerstrцm Test for Nicotine Dependence Answer the two questions below. Check your total score against the scoring key. 1. How soon after waking do you smoke your first cigarette? Less than five minutes (3 points) 5 to 30 minutes
(2 points) 31 to 60 Minutes
(1 point) 2. How many cigarettes do you smoke each day? More than 30 cigarettes (3 points) 21 to 30 cigarettes (2 points) 11 to 20 cigarettes (1 point) SCORING KEY: 5 to 6 points = heavy nicotine dependence; 3 to 4 points = moderate nicotine dependence; 0 to 2 points = light nicotine dependence. FIGURE 1. Abbreviated Fagerstrцm Test for Nicotine Dependence. Family physicians can use this quickly administered tool to evaluate intensity of nicotine dependence or addiction in their patients. Adapted with permission from Rustin TA. Pharmacologic treatment of nicotine dependence. In: The certification review course in addiction medicine for the American Society of Addiction Medicine. Chevy Chase, Md.: American Society of Addiction Medicine, 1998; based on information in Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrцm KO. The Fagerstrцm Test for Nicotine Dependence: a revision of the Fagerstrцm Tolerance Questionnaire. Br J Addict 1991;86:1119-27.
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Smoking Cessation Include "Do you smoke?" with questions routinely asked while taking the patient's vital signs.
The patient is a smoker. Assess the patient's nicotine dependence using the modified CAGE questionnaire (see Table 1) and/or the abbreviated Fagerstrцm test (see Figure 1). Use the five-stage transtheoretical model to assess the patient's readiness to change. Precontemplation stage (the patient thinks smoking is not a problem) Interventions: Educate the patient about the effects of smoking, introduce ambivalence (inquire about decision to continue smoking), express concern, and recommend quitting. Physician statement introducing ambivalence: "Today most people agree that smoking is not good for your health. What do you think about that?" Physician statement expressing concern and encouraging contemplation: "I am concerned about your health and believe you should stop smoking. I am wondering how I can help you with that."
The patient is a nonsmoker. Reinforce the patient's healthy choice.
Contemplation stage (the patient thinks smoking may be a problem) Interventions: Assess positive and negative thinking about smoking. Physician statement resolving ambivalence: "Your cough will improve when you quit smoking."
Preparation stage (the patient wants to quit smoking) Interventions: Set a quit date, select smoking cessation strategies, determine dosage of nicotine replacement if indicated, identify triggers, gather social support
for quitting, and begin bupropion (Zyban) if indicated. Physician statement encouraging planning and action: "Let's set a date for you to quit smoking and make plans for how you can do it."
Action stage (the patient quits smoking) Interventions: Begin nicotine replacement and continue bupropion. Physician and staff maintain frequent contact with the patient to provide support and help provide solutions for dealing with specific triggers.
Maintenance stage (the patient remains off smoking) Intervention: Continue positive reinforcement of the healthy choice.
Relapse (the patient starts smoking again) Interventions: Reassess readiness to change and enter at appropriate stage; identify reasons for relapse and consider how things might be done differently. Physician supports another attempt and, when the patient is ready, works with the patient to develop a more effective smoking cessation plan.
FIGURE 2. A suggested approach to smoking cessation, based on the transtheoretical model for readiness to change.
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nence. Healthy substitution behaviors may help to prevent relapse. A suggested approach to smoking cessation, based the transtheoretical model, is outlined in Figure 2. Pharmacotherapy signs and symptoms
of nicotine withdrawal include irritability, anxiety, decreased heart rate
, increased appetite, food cravings, restlessness, and difficulty concentrating.15 In patients with moderate or high nicotine dependence (Figure 1),8,9 medications that lessen these signs and symptoms can help to prevent relapse in the early stages of smoking cessation10 (Table 2). NICOTINE REPLACEMENT Nicotine replacement by any delivery system has been shown to double the smoking cessation rate.16 Currently, four forms of nicotine delivery are available: patch, gum, inhaler, and nasal spray. Some data indicate that use of a combination of delivery methods, such as the gum and the patch, may be useful in heav-
ily nicotine-dependent smokers.17 Nicotine replacement is initiated on the quit date. Nicotine Patch. A number of transdermal nicotine replacement systems (Habitrol, Nicoderm CQ, Nicotrol) are available over the counter. The results of the Fagerstrцm Test for Nicotine Dependence can be used to determine the appropriate starting patch strength for a patient.9 However, the proper initial dose can be determined more quickly using the patient's score on the abbreviated Fagerstrцm test (Figure 18,9): a score of 5 to 6 warrants use of the 21-mg nicotine patch; a score of 3 to 4 means that the 14-mg nicotine patch is appropriate for initial therapy; and a score of zero to 2 indicates initial use of the 7-mg nicotine patch.8 adverse reaction
s to transdermal nicotine replacement systems seldom cause discontinuation of therapy. From 30 to 50 percent of patients experience mild skin irritation under the patch. In most patients, this problem can be alleviated by rotating patch application sites. Sleep disruption is usually resolved by removing the patch at bedtime.16
TABLE 2 Effective Pharmacotherapy for Nicotine Withdrawal
Drug and delivery system Initial dosage
Nicotine replacement Patch (Habitrol, Nicoderm CQ, Nicotrol) Gum, 4-mg strength (Nicorette) Inhaler (Nicotrol Inhaler)
One patch per day (21 mg, 14 mg, or 7 mg, depending on degree of nicotine dependence) 10 to 15 pieces per day Four inhalers per day
Nasal spray (Nicotrol NS) Four sprays per hour
150 mg per day for 3 days
Duration of therapy
Taper to next lowest patch strength in 4 to 6 weeks.
8 to 12 weeks $89 to 124
Five to eight pieces per day Four inhalers per day, with gradual tapering of use Eight to 80 sprays per day, with gradual tapering of use
8 weeks to
8 to 12 weeks 123
8 to 12 weeks $170 to 255 (four to six bottles)
150 mg twice daily
8 to 12 weeks 96
*--Estimated cost to the pharmacist for 30 days of treatment, based on average wholesale prices (rounded to the nearest dollar) in Red book. Montvale, N.J.: Medical Economics Data, 2001. Cost to the patient will be higher, depending on prescription filling fee.
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It is important to discourage patients from smoking while they are using the nicotine patch. The combination of smoking and nicotine patch use results in discomfort from higher nicotine levels; more importantly, it increases the likelihood of relapse to virtually 100 percent.18 Concerns about sudden cardiac death as a result of concomitant smoking and nicotine patch use have been allayed by two Clinical Trials
19,20 that showed no increase in morbidity or mortality associated with nicotine patch use in smokers with heart disease. Nicotine patches should be used for about eight to 12 weeks. Tapering to the next lowest dose (e.g., 21 mg to 14 mg) can be done after four to six weeks. The patient who starts with the 7-mg patch should continue using that patch for six weeks. Nicotine Gum. Nicotine polacrilex (Nicorette) is available over the counter in 2-mg and 4-mg strengths. The gum is most effective in the 4-mg strength, with initial use of 10 to 15 pieces of gum per day. After two weeks, most patients can change to the 2-mg strength. The most important adverse events
associated with nicotine gum appear to be gastrointestinal side effects from swallowing large amounts of nicotine when the gum is used improperly. Nicotine gum is intended to be parked in the buccal area and chewed once or twice every few minutes. If the gum is chewed too quickly, nicotine is swallowed with saliva, and nausea or dyspepsia can result. Nicotine Inhaler. A nicotine inhalation system (Nicotrol Inhaler) has recently become The Author ROBERT MALLIN, M.D., is assistant professor in the Department of Family Medicine at the Medical University of South Carolina, Charleston. He received his medical degree from the University of South Carolina School of Medicine, Columbia, where he also completed a family practice residency at Richland Memorial Hospital. Dr. Mallin is board certified in family practice and is also certified by the American Society of Addiction Medicine. Address correspondence to Robert Mallin, M.D., Department of Family Medicine, Medical University of South Carolina, 295 Calhoun St., P.O. Box 250192, Charleston, SC 29425 (e-mail: [email protected]
). Reprints are not available from the author.
available by prescription. The nicotine is primarily absorbed through the oral cavity (36 percent) and the esophagus and stomach (36 percent), rather than through the lungs (4 percent). Currently, four inhalers a day must be used to achieve adequate nicotine levels. Hence, frequent dosing is required, with each inhaler containing 500 puffs. Side effects include mouth and throat irritation.21 Nicotine Nasal Spray. Nicotine replacement can also be accomplished with a nasal spray (Nicotrol NS), which is available by prescription. The use of four sprays per hour or a maximum of 80 sprays per day is recommended. Nasal and throat irritation, rhinorrhea, and nausea are common side effects. Comparison of Delivery Systems. Data are lacking on which nicotine delivery system is most effective. Because all four systems appear to be efficacious, patient preference usually determines the choice of nicotine replacement modality. For example, the patient who needs to be doing something with his or her hands may prefer the nicotine inhaler over the nicotine patch. The patient who is concerned about gaining weight may prefer to use nicotine gum, which has been shown to delay (but not prevent) weight gain associated with smoking cessation.22 BUPROPION Bupropion and nicotine replacement have been shown to have similar positive effects on quit rates. Combined use of these agents appears to be the most effective treatment for nicotine dependence. Bupropion inhibits the uptake of norepinephrine, serotonin, and dopamine. The mechanism by which bupropion enhances the ability of patients to abstain from smoking is unknown; however, the drug is believed to reduce the urge to smoke through its effect on the norepinephrine and dopamine neurotransmitter systems. One controlled trial5 found that bupropion therapy resulted in a 12-month abstinence rate of 30 percent, compared with 16 percent
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for nicotine replacement therapy alone. Combination therapy using bupropion plus nicotine replacement resulted in an even higher 12-month quit rate (36 percent). Bupropion therapy is initiated in a dosage of 150 mg per day for three days. The dosage is then increased to 150 mg twice daily. The quit date should be set for one to two weeks after bupropion therapy is initiated. Bupropion therapy is usually continued for eight to 12 weeks after the patient has quit smoking. Contraindications to the use of bupropion include a history of seizure disorder and the presence of eating disorders or uncontrolled hypertension. The most common side effects of the drug are dry mouth and sleep disturbance
. Nicotine-dependent patients with comorbid depression may benefit from bupropion therapy.22 OTHER DRUGS Silver acetate, which causes cigarettes to have a bad taste, has been used as a smoking cessation aid for many years. The literature contains no support for this agent as an effective adjunct.23 Alprazolam (Xanax) and other benzodiazepines have been used to reduce the anxiety associated with nicotine withdrawal. However, treatment with benzodiazepines has not been shown to improve smoking cessation rates. Clonidine (Catapres) initially appeared to be useful in the treatment of nicotine withdrawal,24 but long-term quit rates did not improve when this drug was used alone.15 The addition of mecamylamine (Inversine), a ganglionic blocker classified as an antihypertensive agent, to transdermal nicotine replacement has been shown to improve the abstinence rate in smokers, compared with use of the patch alone.25 Dealing with Relapse Most patients relapse within the first six to 12 months of a smoking cessation attempt. If a patient relapses, the physician needs to encourage the patient to try again. It is useful
If bupropion is to be used in smoking cessation, the drug should be started one to two weeks before the planned quit date. to review the treatment plan to determine what did and did not work. A patient may not return immediately after a relapse and may smoke for months before another visit. At that point, the patient's readiness to change needs to be reevaluated, and the smoking cessation process must be repeated. Nicotine dependence is a tenacious and difficult addiction to treat successfully. Clearly, perseverance on the part of the patient and the physician is most effective for achieving permanent abstinence. The use of nicotine replacement and bupropion can improve results, and the application of readiness-tochange strategies and motivational interviewing techniques are essential for success. Behavioral therapy and support in a group setting have been shown to improve quit rates. Individual counseling can also be effective. A supportive telephone call during the first few days of abstinence may help the patient who is trying to quit smoking.26,27 The author indicates that he does not have any conflicts of interest. Sources of funding: none reported. REFERENCES 1. State-specific prevalence of cigarette smoking among adults, and children's and adolescents' exposure to environmental tobacco smoke--United States, 1996. MMWR Morb Mortal Wkly Rep 1997; 46:1038-43. 2. Rigotti NA, Lee JE, Wechsler H. US college student
s' use of tobacco products: results of a national survey. JAMA 2000;284:699-705. 3. Cigarette smoking among adults--United States, 1993. MMWR Morb Mortal Wkly Rep 1994;43: 925-30. 4. Jorenby DE, Fiore MC. The Agency for health care
Policy and Research smoking cessation clinical practice
guideline: basics and beyond. Prim Care 1999;26:513-28. 5. Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, et al. A controlled trial of
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sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999; 340:685-91. 6. Fiore MC. Smoking cessation. Rockville, Md.: U.S. Dept. of Health and Human Services, Public health service
, Agency for Health Care Policy and Research, Centers for Disease Control
and Prevention, 1996. Clinical practice guideline no. 18; AHCPR publication no. 96-0692. 7. Lairson DR, Harrist R, Martin DW, Ramby R, Rustin TA, Swint JM, et al. Screening for patients with alcohol problems: severity of patients identified by the CAGE. J Drug Educ 1992;22:337-52. 8. Rustin TA. Pharmacologic treatment of nicotine dependence. In: The certification review course in addiction medicine for the American Society of Addiction Medicine. Chevy Chase, Md.: American Society of Addiction Medicine, 1998. 9. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrцm KO. The Fagerstrцm Test for Nicotine Dependence: a revision of the Fagerstrцm Tolerance Questionnaire. Br J Addict 1991;86:1119-27. 10. Rustin TA. Assessing nicotine dependence. Am Fam Physician 2000,62:579-84,591-2. 11. Prochaska JO, DiClemente CC, Norcross JC. In search of how people change. Applications to addictive behaviors. Am Psychol 1992;47:1102-14. 12. Barnes HN, Samet JH. Brief interventions with substance-abusing patients. Med Clin North Am 1997;81:867-79. 13. Miller WR, Rollnick S. Motivational interviewing: preparing people to change addictive behavior. New York: Guilford, 1991. 14. Fiore MC, Novotny TE, Pierce JP, Giovino GA, Hatziandreu EJ, Newcomb PA, et al. Methods used to quit smoking in the United States. Do cessation programs help? JAMA 1990;263:2760-5. 15. Rustin TA. Management of nicotine withdrawal. In: Graham AW, Schultz TK, Wilford BB, eds. Principles of addiction medicine. 2d ed. Chevy Chase, Md.: American Society of Addiction Medicine, 1998: 487-95. 16. Prochazka AV. New developments in smoking cessation. Chest 2000;117(4 suppl):169S-75S.
17. Kornitzer M, Boutsen M, Dramaix M, Thijs J, Gustavsson G. Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med 1995;24:41-7. 18. Gourlay SG, Forbes A, Marriner T, Pethica D, McNeil JJ. Prospective study of factors predicting outcome of transdermal nicotine treatment in smoking cessation. BMJ 1994;304:842-6. 19. Joseph AM, Norman SM, Ferry LH, Prochazka AV, Westman EC, Steele BG, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996; 335:1792-8. 20. Nicotine replacement therapy for patients with coronary artery disease. Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease. Arch Intern Med 1994;154: 989-95. 21. Fant RV, Owen LL, Henningfield JE. Nicotine replacement therapy. Prim Care 1999;26:633-52. 22. A clinical practice guideline for treating tobacco use and dependence: a US Public Health Service report. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. JAMA 2000;283:3244-54. 23. Lancaster T, Stead LF. Silver acetate for smoking cessation. Cochrane database
Syst Rev 2000;(2): CD000191. 24. Glassman AH, Jackson WK, Walsh BT, Roose SP, Rosenfeld B. Cigarette craving, smoking withdrawal, and clonidine. Science 1984;226:864-6. 25. Rose JE, Behm FM, Westman EC, Levin ED, Stein RM, Ripka GV. Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. Clin Pharmacol
Ther 1994;56:86-99. 26. Lancaster T, Stead LF. Individual behavioural counselling for smoking cessation. Cochrane Database Syst Rev 2000;(2):CD001292. 27. Carlson LE, Taenzer P, Koopmans J, Bultz BD. Eightyear follow-up of a community-based large group behavioral smoking cessation intervention. Addict Behav 2000;25:725-41.
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