Megan E. Wren
GENERAL PRINCIPLES
Smokers Can Quit
· Since the publication of the first Surgeon General’s Report on Smoking and Health in 1965, the rate of smoking among adult Americans has gradually decreased from 42% down to 19%.1
· Over time, the average number of cigarettes smoked per day has declined to 15; now, fewer than 10% smoke 30 or more cigarettes per day (one pack contains 20 cigarettes).1
· Among current smokers, more than two-thirds report that they want to quit and just over half have made a quit attempt in the past year.2
· Smokers wanting to quit have to overcome both a strong habit and a physiologic addiction to nicotine.
o Nicotine from cigarette smoke reaches the brain in <10 seconds.3 This rapid delivery to the mesolimbic reward system makes smoking very addicting. Because nicotine has a half-life of just 30 minutes, the smoker soon craves another cigarette.
o Smoking is also a conditioned behavior—the act of smoking is quickly rewarded with pleasurable feelings—the satisfaction of smoking. This conditioning is also tied to cues in the environment: certain places, times, or events are strong triggers for a desire to smoke.
· Since tobacco use is both a learned behavior and a physical addiction to nicotine for the majority of smokers, the combination of counseling and pharmacologic therapies can produce higher quit rates than either one alone.
· The clinician should recognize tobacco dependence as a chronic disease, subject to periods of remission and relapse, and requiring ongoing counseling. Fortunately, effective interventions are now available that may increase abstinence rates to 20% to 30%.4
· Although individual quit attempts have a low success rate, many people can be successful with repeated attempts. In fact, of all Americans who have smoked, half have successfully quit.2
Guidelines
· Multiple organizations partnered to develop a clinical practice guideline summarizing evidence-based recommendations on the treatment of tobacco use. It was published as a U.S. Public Health Service (PHS) Report and is available online at http://www.ahrq.gov/professionals/clinicians-providers/guidelines-recommendations/tobacco/clinicians/update/index.html (last accessed 1/14/15).
· Key recommendations of the PHS guideline include the following:
o Tobacco dependence is a chronic condition that often requires repeated intervention and multiple attempts to quit. Effective treatments exist that can significantly increase rates of long-term abstinence.
o It is essential to consistently identify and document tobacco use status and treat every tobacco user seen in a health care setting.
o Tobacco dependence treatments are effective. Clinicians should encourage every patient willing to make a quit attempt to use the counseling treatments and medications recommended in this guideline.
o Even brief tobacco dependence treatment is effective and should be offered to every patient who uses tobacco.
o Individual, group, and telephone counseling is effective; their effectiveness increases with treatment intensity (time). Two components of counseling are especially effective:
§ Practical counseling (problem solving/skills training)
§ Social support delivered as part of treatment
o Numerous effective pharmacotherapies for smoking cessation now exist. Except in the presence of contraindications, these should be used with all patients attempting to quit smoking.
o The combination of counseling and medication is more effective than either alone. Clinicians should encourage all individuals making a quit attempt to use both counseling and medication.
o If a tobacco user is unwilling to make a quit attempt, clinicians should use motivational treatments shown to be effective in increasing future quit attempts.
o Telephone quitline counseling is effective with diverse populations and has broad reach.
Counseling for Behavior Change
· Brief counseling should be provided to all smokers at every visit. Interventions as short as 3 minutes can increase quit rate significantly.
· The five As technique for brief office counseling of smokers is familiar to many clinicians. A brief summary is provided below; more detail is available in the PHS Report, pages 37 to 43.4
o ASK: Ask about smoking… every patient, every visit. Make it one of the vital signs so it isn’t forgotten.
o ADVISE: Advise all smokers to quit. Physicians’ advice is a strong incentive to attempt smoking cessation.
§ Be empathetic, not confrontational.
§ Use a clear, strong message such as, “Quitting smoking is the most important thing you can do to protect your health now and in the future. I can help you.”
§ Personalize the message by stressing the relevance to the patient’s current medical problems and symptoms. Most smokers are unaware of smoking’s connection with a wide array of problems from acid reflux to osteoporosis to macular degeneration, as well as vascular disease and many cancers.
o ASSESS: Assess the smoker’s willingness to make a serious quit attempt in the next 30 days (see “Readiness for Change” below).
o ASSIST: Assist in the quit attempt. If the patient is ready to make a serious attempt to quit, then make smoking cessation the focus of the visit. Three elements of successful smoking cessation treatment strategies include social support, pharmacologic therapy, and skills training or problem-solving techniques.
§ Help the patient set a specific quit date in the next couple of weeks. Write it in the chart and on a prescription pad to make it an official commitment.
§ Review prior quit attempts. What worked? What didn’t work and may have contributed to relapse?
§ The patient should enlist the aid of family and friends.
§ Discuss anticipated triggers and challenges, and strategies to cope with them (see “Challenges and Strategies” below). Anticipate nicotine withdrawal symptoms, cues to smoking, and danger situations.
§ Before the quit date, he/she should start to break the habit by avoiding smoking in the usual places. Make the home and car smoke free.
§ Provide educational materials. Offer referrals to classes, websites such as www.smokefree.gov, or a telephone quitline (1-800-QUIT-NOW) for additional counseling.
§ Recommend pharmacotherapy, unless contraindicated.
o ARRANGE: Arrange follow-up in person or by phone within the first week and again within the first month.
§ Successful quitters should be congratulated and reminded to be on guard against tempting situations and cravings, which can persist for months to years.
§ Those who did not try to quit should be assessed for willingness to change and encouraged to again set a quit date when ready.
§ Those who quit and have relapsed should be encouraged to learn from the experience.
§ Focus on the positive (congratulate for the days or weeks of abstinence).
§ Educate that “a lapse is not a relapse”; encourage the patient to try again.
§ Help the patient feel empowered to try again by discussing strategies to cope with challenging situations.
· Readiness for change: The Prochaska model of stages of change provides a useful framework for targeting interventions to the smoker’s willingness to attempt to quit. Knowing the patient’s readiness for change can guide the physician’s time allotment to counseling in each visit. See Chapter 46 for a more detailed overview of the stages of change.
Challenges and Strategies
· Practical counseling should be provided.
o Review past quit attempts including identification of what helped during the quit attempt and what factors contributed to relapse.
o Tobacco users who have failed in previous quit attempts should be told that most people make repeated quit attempts before they are successful.
o Discuss challenges/triggers and how the patient will successfully overcome them. Advise the removal of all tobacco from home, car, and work environment.
o Because alcohol can cause relapse, the patient should consider limiting/abstaining from alcohol while quitting.
o Quitting is more difficult when there is another smoker in the household. Patients should encourage housemates to quit with them or not smoke in their presence.
· Strategies to help with lifestyle changes include:
o Counterconditioning—substitute other activities or experiences when tempted by cravings or stress.
o Stimulus control—avoid situations that are likely to produce temptation or pressure.
o Reinforcement management—reward small successes.
· Withdrawal symptoms include irritability, dysphoria, restlessness, anxiety, difficulty concentrating, headache, insomnia, and increased appetite. Educate the patient that the withdrawal symptoms will abate over a few weeks. Smoking cessation also triggers cravings for cigarettes, which can last for months to years. Cravings, although intense, are usually brief. A few minutes of distraction can help the patient ride out the craving—deep breathing, exercise, or a change in activity can all be helpful.
· Delayed quitting can occur. In a study with over 2,000 participants on varenicline, bupropion, or placebo, the authors found that about 60% of successful quitters were continuously abstinent by week 2, while about 40% were “delayed quitters” who smoked during 1 or more weeks in weeks 2 to 8.5 This suggests that smokers who are motivated to quit should continue treatment despite lack of early success.
· Weight gain is a concern for many patients contemplating smoking cessation.
o Often cited as 2 to 3 kg, the actual weight gain is quite variable. A recent meta-analysis found a mean weight gain of 4 to 5 kg after a year of abstinence, but roughly one-third gained <5 kg, one-third gained 5 to 10 kg, and 14% gained >10 kg. Of note, 16% to 21% actually lost weight.6
o Exercise has been shown in some studies to reduce cigarette cravings and tobacco withdrawal symptoms.7
o Pharmacologic therapy with nicotine, bupropion, or varenicline attenuated weight gain in the short term but not at 1 year postcessation.8
· Coughing may temporarily increase in the weeks following smoking cessation as cough reflex sensitivity is restored.9
· Depression and anxiety may be exacerbated in patients with a history of psychiatric illness. Those patients should be offered counseling and/or medications.
· Cost is an issue for many patients; smoking cessation products are expensive, and insurance coverage is variable.
o Since bupropion is an antidepressant, it is more likely to be covered by insurance plans.
o Some smoking cessation products are available through quitlines or community clinics.
o Smoking cessation products are often less expensive than smoking, but cigarette prices vary considerably: from $4.41/pack in North Dakota to $10.05/pack in New York for monthly costs of $132.00 to $301.00 for 1 pack/day.10
For Patients Unwilling to Quit
· Patients may be unwilling to attempt to quit smoking for many reasons: lack of knowledge, lack of money or health insurance, or fears or concerns about quitting, or they may be demoralized because of previous relapses. Such patients may respond to brief interventions based on principles of motivational interviewing (MI), a patient-centered counseling technique.11
· Clinician lectures or arguments for quitting tend to increase the patient’s resistance to change. MI techniques help patients find their own reasons for change.
· MI techniques focus on exploring the smoker’s feelings, beliefs, and values in an effort to uncover any ambivalence about using tobacco. Once ambivalence is uncovered, the clinician selectively elicits, supports, and strengthens the patient’s “change talk” (e.g., reasons, ideas, and need for eliminating tobacco use) and “commitment language” (e.g., intentions to take action to change smoking behavior, such as not smoking in the home). See Table 45-1 for details.4
TABLE 45-1 General Principles of Motivational Interviewing and Examples of Language to Use
Modified from Fiore MC, Jaen CR, Baker TB, et al. Clinical Practice Guideline. Treating Tobacco Use and Dependence: 2008 Update. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service; 2008. http://www.ahrq.gov/professionals/clinicians-providers/guidelines-recommendations/tobacco/clinicians/update/index.html. Last accessed 1/14/15.
MEDICATIONS
Recommendations
· Pharmacologic therapy can approximately double the quit rate as compared to placebo and should be offered to all patients except in the presence of limited special circumstances (see below).
· First-line treatments include nicotine replacement therapy (NRT), sustained-release bupropion (bupropion SR), and varenicline (see Table 45-2).
TABLE 45-2 Medications to Aid Smoking Cessation
aInformal survey of prices in several pharmacies in the St. Louis, MO area, January, 2013.
bNot FDA approved for smoking cessation.
OTC, over the counter; ppd, pack per day; Rx, by prescription only; TTFC, time to first cigarette after waking.
Nicotine Replacement Therapy
· NRT provides an alternative source of nicotine to ease withdrawal symptoms while the patient learns new nonsmoking behaviors. Many studies have documented that the use of NRT can increase long-term success rates 1.5-fold (nicotine replacement gum) to 2-fold (other NRT) compared to placebo.4
· NRT is most effective when combined with counseling. The effectiveness of counseling increases with the intensity of treatment, but even brief interventions are of benefit.
· Some experts advocate so-called harm reduction—the use of NRT for as long as it takes to keep patients from smoking.12
Safety of Nicotine Replacement Therapy
· Smokers smoke in order to get nicotine, but essentially all of the adverse health effects of smoking stem from other constituents in tobacco and its smoke. Thus, a cigarette is a contaminated drug delivery device. Cigarette smoke contains over 4,000 chemical compounds (the tar), ranging from carbon monoxide to hydrogen cyanide, and 69 of which are known carcinogens, including arsenic, benzene, and polonium 210.13
· The dose-response relation for nicotine is flat making the effects of smoking plus NRT similar to smoking alone.
· NRT is a safe alternative to cigarettes and does not cause heart attacks, lung cancer, or asthma, as some have claimed.14
· The most common side effect of nicotine is local irritation, such as a rash under a nicotine patch or throat irritation from inhaled nicotine.
· Overuse of nicotine, whether from smoking or from NRT, can cause symptoms of nausea, vomiting, dizziness, sweating, palpitations, or anxiety.
· Massive overdose can cause seizures and cardiovascular collapse. All nicotine-containing products should be disposed of out of reach of small children and pets to avoid accidental poisoning. NRT is unlikely to cause addiction due to the low level of nicotine (<="" li="">
Safety of NRT in Patients with Cardiovascular Disease
· Oxidizing chemicals in smoke likely contribute to an increased risk of thrombotic complications and reduction in nitric oxide availability.4 Unlike cigarette smoking, NRT does not cause platelet aggregation or thrombotic complications.15
· Transdermal nicotine in smokers with known coronary artery disease (CAD) has been shown to cause no significant differences in heart rate, in blood pressure, or in duration or frequency of ischemic episodes on ambulatory ECG monitoring.16
· NRT use was not associated with an increased risk of adverse cardiovascular events in the first year after acute coronary syndrome (ACS).17
· The use of nicotine gum did not increase cardiovascular deaths or hospitalizations, even in patients who smoked while using NRT and/or used NRT for more than a year.18
· Stress testing in smokers with known CAD showed that addition of a nicotine patch improved exercise tolerance and decreased ischemia, despite continued smoking and increased serum nicotine levels. The reduction in ischemia correlated with reduced exhaled carbon monoxide levels, as the subjects spontaneously reduced their smoking while wearing the nicotine patches.19,20 This clearly shows that smoking while wearing a nicotine patch is not dangerous.
· NRT use in high-risk smokers hospitalized with ACS or decompensated heart failure was safe and was associated with a decrease in readmissions and a decrease in all-cause mortality.21
· The American Heart Association and the American College of Cardiology support the use of NRT to aid in smoking cessation in patients with atherosclerotic vascular disease.22–24
Assessing Nicotine Dependence
· An estimate of a person’s dependence on nicotine can guide dosing of NRT. Plasma levels of nicotine and cotinine vary from person to person, and only weakly correlate with the number of cigarettes smoked per day. A study in regular smokers found that among 1 pack per day (ppd) smokers, plasma cotinine levels varied 74-fold.25
o Highly dependent persons smoke within 30 minutes of waking and typically smoke >one-half ppd.
o Persons with low nicotine dependence wait more than 30 minutes for the first cigarette of the day and usually smoke <1 ppd.
· On an adequate dose of NRT, the patient will still have cravings but should feel relatively comfortable between cravings. If the NRT dose is too low, the patient will experience ongoing withdrawal symptoms and strong cravings. If the dose is too high, the patient will experience symptoms of nicotine overdose.
Specific Products
· Nicotine gum (polacrilex) is available over the counter in 2-mg and 4-mg strengths; the 4-mg strength is recommended for those who smoke more than 1 ppd and/or smoke within 30 minutes of awakening.
o The nicotine is absorbed only through the buccal mucosa, and absorption is decreased by acidic beverages, so the patient should be instructed not to eat or drink while chewing the gum or 15 minutes before. Eating or drinking or rapid chewing will cause the nicotine to be swallowed, and it will cause heartburn, hiccups, or dyspepsia.
o The gum should be chewed slowly until a peppery taste emerges, then left between the cheek and gum for buccal absorption. The gum should be chewed slowly and intermittently for approximately 30 minutes or until the taste dissipates.
o It takes several minutes for the nicotine to reach the bloodstream, so there will not be the immediate satisfaction of smoking.
o Patients will be more successful if they use at least 9 pieces a day.26,27 They should use it on a fixed schedule, one piece every 1 to 2 hours for at least 1 to 3 months, then start to slowly taper the number of pieces per day (one piece per day every 4 to 7 days). The maximum daily dose is 24 pieces. Common side effects include mouth soreness, dyspepsia, and hiccups.
· Nicotine lozenges are available over the counter in 2-mg and 4-mg strengths; the 4-mg strength is recommended for those who smoke within 30 minutes of awakening.
o Similar to the nicotine gum, the nicotine is absorbed through the buccal mucosa, so patients must not eat or drink while using it.
o Patients will be more successful if they use at least 9 pieces a day: 1 piece every 1 to 2 hours for at least 1 to 3 months, then taper off. The maximum daily dose is 24 pieces. Side effects include mouth soreness, dyspepsia, and hiccups.
· Nicotine patches are available over the counter in several strengths, typically 21, 14, or 7 mg/day.
o Most patients should start with the strongest patch, unless they smoke <10 cigarettes/day and wait more than 30 minutes to smoke after awakening. The highest strength patch is used for 2 to 6 weeks, then the intermediate strength for 2 weeks, and then the lowest strength for 2 weeks.
o Highly dependent smokers may need 2 or more full-strength patches for adequate replacement therapy.
o Each morning, a patch should be placed on a relatively hairless location on the trunk or upper arm (hair may be shaved). Locations should be rotated to minimize skin irritation. Hands should be washed after handling patches. The used patch should be folded in half and thrown away out of reach of children and pets.
o Patches either may be used overnight to minimize morning cravings or may be taken off at bedtime to minimize insomnia and vivid dreams. If the patch is not worn overnight, morning withdrawal symptoms may be treated with a faster-acting form of nicotine.
o The most common side effects include insomnia and skin irritation. It is common to feel tingling under the patch for the first hour.
· Nicotine nasal spray is available by prescription only and is less popular with patients (expensive and awkward to use).
o The spray has a faster onset of action than the gum or patch and therefore has greater potential for dependence.
o The most common side effect is nasal irritation, which can be minimized by avoiding sniffing or inhaling while administering.
o Patients should use one spray in each nostril (for a total dose of 1 mg) and should use 1 to 2 doses/hour with a maximum of 40 doses/day.
· Nicotine inhalers are available by prescription only and are also less popular with patients (expensive and awkward to use).
o Each cartridge delivers 4 mg nicotine over 80 inhalations. Patients should use 6 to 16 cartridges daily for up to 6 months. The vapor is absorbed in the mouth and throat and has a fairly fast onset of action. The inhaler is puffed frequently for 20 minutes (much more frequently than a cigarette).
o Because the nicotine is absorbed only through the buccal mucosa and absorption is decreased by acidic beverages, the patient should be instructed not to eat or drink while using the inhaler or 15 minutes before.
o The most common side effects are irritation of the mouth and throat, coughing, dyspepsia, and rhinitis.
Nonnicotine Medications
Bupropion
· Bupropion SR is thought to work by enhancing dopaminergic activity in the central nervous system.
· In randomized controlled trials, subjects treated with bupropion SR had abstinence rates of about twice that of the placebo group.28 Efficacy is independent of a history of depression.
· Bupropion SR should be started 1 to 2 weeks before the quit date at 150 mg each morning for 3 days, then 150 mg twice daily for 7 to 12 weeks. Evening dosing may lead to insomnia so the second dose should be in the late afternoon. A lower dose of 150 mg once daily may be as effective as twice-daily dosing.29
· Studies have used bupropion for 7 to 52 weeks. Longer duration was associated with delay and attenuation of relapse and weight gain.30
· The most common side effects are insomnia (about 20%), dry mouth, and nausea.
· Due to a risk of seizures (approximately 1 in 1,000), bupropion SR should not be used in patients with a history of seizure, head trauma, and brain tumor; in those with anorexia/bulimia and hepatic failure; or in those using drugs that may increase the risk of seizures (theophylline, systemic steroids, antipsychotics, antidepressants, hypoglycemics/insulin, or abuse of alcohol or stimulants).
· Bupropion SR is contraindicated in patients with use of a monoamine oxidase inhibitor within 14 days.
· In 2008, the U.S. Food and Drug Administration (FDA) warned of neuropsychiatric symptoms and suicidal events, even in individuals with no history of psychiatric disease, based on postmarketing reports.31 Patients should be monitored for changes in behavior, hostility, agitation, depressed mood, or suicidal ideation.
Varenicline
· The newest medication approved for smoking cessation is varenicline, a partial nicotine agonist. It binds to the α4β2-nicotinic acetylcholine receptors, stimulating dopamine release to reduce craving and withdrawal symptoms while also blocking binding of nicotine to reduce the reinforcing effects of smoking (satisfaction).
· Varenicline has been shown to more than double the placebo quit rate and may be more effective than bupropion.4,32,33
· Varenicline should be started at least a week prior to the patient’s quit date at 0.5 mg once daily for 3 days, then 0.5 mg twice daily for 4 days, and then 1 mg twice daily. Varenicline should be continued for 12 weeks; successful quitters may be continued for an additional 12 weeks to reduce relapses.
· The most common adverse effects of varenicline were nausea (in more than one-quarter patients), headache, vomiting, flatulence, insomnia, abnormal dreams, and dysgeusia. Nausea is reduced when varenicline is taken with food and a glass of water.
· The FDA has warned of neuropsychiatric symptoms and suicidal events, even in individuals with no history of psychiatric disease, based on postmarketing reports.31 Patients should be monitored for changes in behavior, hostility, agitation, depressed mood, or suicidal ideation. The FDA also warned that patients taking varenicline may experience impairment of the ability to drive or operate heavy machinery.34
· In 2011, the FDA warned that varenicline may increase the risk of adverse cardiovascular events in patients with known cardiovascular (CV) disease.35 This was based on a trial that showed a nonsignificant increase in CV events.36 A 2011 meta-analysis showed a statistically significant increase in CV events, while a 2012 meta-analysis showed no statistically significant difference in rates of CV events with varenicline.37,38 A large prospective cohort study published in 2012 showed no increase in the risk of major cardiovascular events in varenicline users versus bupropion.39
Other Medications
· Nortriptyline is considered a second-line agent.
o It is not FDA approved for smoking cessation, but there have been several published reports that demonstrate efficacy in smoking cessation that exceeds placebo but is less than bupropion.40
o As with other tricyclic antidepressants, nortriptyline often causes dry mouth, constipation, and sedation.
o An advantage of nortriptyline is its affordability.
· Clonidine is considered a second-line agent.
o Clonidine can approximately double the quit rate and is inexpensive. However, it is rarely used for smoking cessation due to troublesome side effects including dry mouth, sedation, and orthostatic hypotension. Abrupt cessation of high-dose clonidine can cause rebound hypertension.
o For smoking cessation, clonidine is usually used at low doses, 0.1 to 0.2 mg twice daily.
· Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are not effective for smoking cessation.
Combination Therapy
· Combination therapy with the nicotine patch and a faster-acting form (gum, lozenge, spray, inhaler) has been shown to be more effective than with either alone.4,41
· Bupropion combined with NRT is more effective than with either alone.4,21,42
Special Circumstances
Pregnancy and Lactation
· Clinicians should provide intensive counseling to help pregnant and lactating women quit smoking.
· Nicotine gum is rated category C, and the patches are rated category D, but the circulating nicotine levels are only about half those seen in pack-a-day smokers, and NRT lacks the carbon monoxide and toxic chemicals of tobacco smoke.
o It has been suggested that NRT be considered if prior attempts to quit have been unsuccessful and the patient continues to smoke while pregnant.43
o The American Congress of Obstetricians and Gynecologists (ACOG) opinion states that NRT “must be used under close medical supervision and only after weighing the known risks of smoking against the possible risks of the NRT during pregnancy.”44
o Each patient should be informed about the presumed risks and benefits.
· Bupropion is rated as category C. ACOG reviewed the literature on the use of antidepressants during pregnancy and concluded that the limited data available do not suggest an increased risk of fetal anomalies or adverse pregnancy events with bupropion.45
· Varenicline is rated as category C. There are no studies of its use in pregnancy.
Cardiovascular Disease
· NRT has been extensively studied and has been found to be safe for patients with stable coronary artery disease and to actually decrease myocardial ischemia (see above section on “Safety of NRT in Patients with Cardiovascular Disease”).
· Bupropion has been found to be safe and effective in a study of patients hospitalized with ACS or decompensated heart failure.21 The intervention group received counseling plus bupropion and/or NRT (47% used bupropion with or without NRT). Over the 2-year follow-up period, the intervention patients had less than half as many readmissions and only one-quarter of the mortality rate; the absolute risk reduction in mortality was 9.2% with a number needed to treat of 11.
· Bupropion overdose can cause tachycardia, conduction delays, and arrhythmias.
· The studies to date on varenicline in CV patients have had mixed results (see “Varenicline” section above).
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