Smoking Cessation

Tobacco use is the leading preventable cause of morbidity and mortality in the United States. Approximately 440,000 deaths each year are attributed to smoking. It is the most common cause of cancer-related deaths in this country, including deaths from lung cancer, laryngeal cancer, esophageal cancer, oral cancer, and bladder cancer. Tobacco use is also a leading cause of heart disease, stroke, and chronic obstructive pulmonary disease. Research suggests that tobacco use results in more than $157 billion in annual health-related costs.

Definition

Nicotine dependence is characterized by both tolerance and withdrawal symptoms in relation to nicotine use. Nicotine dependence can occur with cigarette smoking, smokeless tobacco use, or cigar or pipe smoking. For the purposes of this chapter, the phrases “quitting smoking” will be used to represent complete abstinence from tobacco products, and “success” will be used to represent lifetime abstinence.

Prevalence and Risk Factors

Fifty-five percent of Americans have tried smoking. Approximately 22.8% of Americans are current smokers and 30% are ex-smokers. The rates of smoking in the general U.S. population decreased from nearly 42% in 1965 to just over 25% in 1990, but the rate of decline has slowed markedly since 1990. Approximately 20% of all Americans meet criteria for nicotine dependence at some point in their lives. Among smokers, 50% to 80% are estimated to meet criteria for nicotine dependence.

Nicotine dependence is more prevalent in persons with mental disorders, especially mood disorders and schizophrenia. According to DSM-IV-TR, 55% to 90% of those with a mental disorder smoke compared with 22% of the general population.

In 2001, 25.2% of U.S. males and 20.7% of females were smokers. There appear to be genetic factors that contribute to nicotine dependence; the risk for those with a first-degree relative who smokes is three times that of those in a family of nonsmokers. In children, depressed mood, poor grades, and antisocial behavior correlate with smoking rates, but the effects of modeling by peers and family are also likely to be critical factors.

Pathophysiology

From the first use of nicotine, physical effects increase the likelihood of repeated nicotine consumption. Nicotine binds to cholinergic receptors in the central nervous system. In response to repeated nicotine use, the receptors rapidly desensitize and increase in number, and both these phenomena conspire to increase the addictive power of nicotine. Dopaminergic neurons within the nucleus accumbens (a brain structure associated with rewards and reinforcement) are activated by projections from nicotine-stimulated neurons. Cell bodies in the ventral tegmental area (a structure associated with perception and modulation of pleasure) are stimulated directly by nicotine, and these neurons project directly to the nucleus accumbens (NAcc). As a result of the widespread neuronal activation, nicotine users experience pleasure, reduced fatigue, increased information-processing ability, reduced anxiety, and other reinforcing effects.

Tolerance develops as the frequency and dose of nicotine use increase. Increasingly desensitized cholinergic receptors on neurons projecting to the NAcc are quickly produced (upregulated) to compensate for the actions of nicotine on the brain. The release of dopamine in the NAcc falls as these desensitized neurons fail to produce the necessary baseline stimulation without the presence of sufficient concentrations of nicotine. Withdrawal symptoms occur when the concentration of nicotine fails to maintain stimulation of the ventral tegmental area and the NAcc. These effects are mediated by increases in noradrenergic outflow from the locus coeruleus and other areas.

Smoking increases the metabolism of several medications, including cyclobenzaprine, naproxen, verapamil, propranolol, and warfarin. Conversely, the blood levels of these medications can increase when smoking cessation is attempted.

Signs, Symptoms, and Diagnosis

The first step in treating nicotine dependence is identifying tobacco users. Practice guidelines for nicotine dependence include those from the U.S. Department of Health and Human Services and the American Psychiatric Association. These guidelines suggest asking patients systematically at each visit whether they use tobacco. This question should be part of an expanded vital signs assessment or in a computer reminder system that is part of the electronic medical record. There is strong evidence that documenting smoking status at every visit increases clinician recognition of nicotine dependence and intervention. The criteria for diagnosis of nicotine dependence follow those for other forms of substance dependence.

The following are DSM-IV-TR criteria for diagnosis of nicotine dependence. The user must demonstrate at least three of the following criteria occurring at the same time during a 12-month period:

Tolerance; signs of tolerance are a need for a markedly increased amount of nicotine to produce the desired effect or a diminished effect with continued use of the same amount of nicotine.
Withdrawal, as manifested by either the characteristic nicotine withdrawal syndrome, or nicotine (or a closely related substance) is taken to relieve or avoid withdrawal symptoms.
Nicotine is used in larger amounts or over a longer period than intended.
The user has a persistent desire or makes unsuccessful attempts to cut down on tobacco.
A great deal of time is spent in obtaining or using the substance (e.g., chain smoking).
Important social, occupational, or recreational activities are reduced because of tobacco use.
Use of the substance continues despite recurrent physical or psychological problems caused or exacerbated by tobacco: for example, continuing to smoke despite diagnoses such as hypertension, heart disease, cancer, bronchitis, and chronic obstructive lung disease.

Nicotine withdrawal is defined by the DSM-IV-TR as a condition in which a person, after using nicotine daily for at least several weeks, exhibits at least four of the following symptoms within 24 hours after reduction or cessation of nicotine use:

Dysphoric or depressed mood
Insomnia
Irritability, frustration, or anger
Anxiety
Difficulty concentrating
Restlessness
Decreased heart rate

Once a diagnosis of nicotine dependence is made, it is useful to characterize the degree to which the patient is physically dependent on smoking. The Fagerström Test for Nicotine Dependence (FTND) (Table 1), can be helpful in determining whether nicotine replacement will be necessary and to what degree. The six-question FTND deals with total tobacco intake and craving severity.

Table 1 Fagerstrom Test for Nicotine Dependence

Question	0 Points	1 Point	2 Points	3 Points
How soon after you wake up do you smoke your first cigarette?	>60 min	31-60 min	6-30 min	<5 min
Do you find it difficult to refrain from smoking in places where it is forbidden, eg, church, library, cinema?	No	Yes
Which cigarette would you hate most to give up?	Any other	First one in the morning
How many cigarettes per day do you smoke?	<10	11-20	21-30	>30
Do you smoke more frequently during the first hours of waking than during the rest of the day?	No	Yes
Do you still smoke if you are so ill that you are in bed most of the day?	No	Yes
Classification of Dependence
0-2	Very low
3-4	Low
5	Moderate
6-7	High
8-10	Very high

Adapted with permission from Heatherton TF, Kozlowski LT, Frecker RC, et al: The Fagerström Test for Nicotine Dependence: A revision of the Fagerström Tolerance Questionnaire. Br J Addict 1991;86:1119-1127.

Treatment

Primary care providers are likely to be most effective in using brief interventions and providing advice and/or prescriptions for pharmacologic interventions. They may also be an important link in providing patients with referrals to more intensive counseling programs and additional education.

Brief Interventions for a Primary Care Setting

Minimal or brief interventions require little cost or time from the provider. There is strong evidence that patients who are consistently advised by health care providers to quit smoking are more likely to take steps to stop. Decision trees (Fig. 1) can be helpful in guiding clinicians through smoking-cessation counseling with patients.

Figure 1: Click to Enlarge

Interventions as short as 3 minutes can substantially increase cessation rates. One common brief intervention designed for health care providers is the five-A method, which involves the following:

Asking about tobacco status at each visit
Advising all tobacco users to quit
Assessing the patient’s willingness to quit
Assisting the patient in quitting
Arranging for follow-up contact

Providers can assess a patient’s readiness to quit using the transtheoretical model of behavior change. If the patient has not thought about quitting or is considering quitting but not in the next few months, they are in the precontemplation or contemplation stage. At this stage, the provider can use motivational interviewing skills to help increase readiness for cessation.

Health care providers can use the five Rs to help enhance a patient’s motivation to quit:

Discuss why quitting is personally relevant.
Identify potential risks associated with smoking.
Identify potential rewards and benefits related to quitting.
Identify potential barriers or roadblocks that might impede the quitting process.
Repeat motivational interventions at each visit.

In general, patients at this stage are unlikely to benefit from advice-giving as much as a nonthreatening discussion of what is keeping them from quitting at this time.

Patients who have made plans to quit or who are in the process of quitting are in the preparation or action stage. These are the patients who will most benefit from brief interventions such as:

Helping the patient identify a “quit date”
Asking the patient to elicit support from friends and family
Having the patient write down the reasons for quitting or coping strategies
Having patients remove tobacco products from their environment
Discussing coping strategies such as replacements (sugar-free gum, water) and distraction (keeping busy, exercising)
Referring the patient to an intensive smoking cessation counseling program
Providing the patient with advice about nicotine replacement and/or discussing use of bupropion or varenicline as a cessation aid

Preventing relapse is important for patients in the maintenance stage (those who have quit smoking). Providers at this stage can educate patients in issues important in preventing relapse, such as being aware of the potential impact of stressful events. In patients who have never smoked, providing reinforcement and encouraging continued abstinence can be effective strategies for prevention. In patients who have relapsed, it is important to deflect guilt and self-doubt with reminders about the frequency of relapse and the need for a renewed commitment to abstinence. Consistently working with patients on smoking cessation increases the chances of success.

Primary care providers may also choose to refer their patients to intensive counseling programs for smoking cessation. Intensive interventions are recommended by national guidelines as first-line treatments and refer to specifically tailored educational programs involving repeated face-to-face contact in an individual or group setting and including a psychotherapy component. More-intensive programs appear to generate better outcomes. Intensive programs help patients cope with nicotine withdrawal through a number of behavioral strategies including using social supports, relaxation training, and cognitive restructuring.

Pharmacologic Options

National guidelines recommend that pharmacologic therapy be considered for all smokers attempting to quit unless the drug is medically contraindicated. Research suggests that pharmacologic interventions are most effective in the context of a behavioral counseling program.

Nicotine Replacement Therapies

Nicotine replacement therapies (NRTs) work by delivering nicotine into the body to ease withdrawal while allowing the smoker to break the behavioral habits associated with the cigarette itself. The fact that 50% of all quitters report withdrawal symptoms makes clear the value in reducing or eliminating the likelihood that these symptoms will impair a quitter’s ability to remain abstinent. Behavioral counseling (either brief or intensive) is an important adjunct to any pharmacologic intervention for smoking cessation.

Nicotine gum is available in 2-mg and 4-mg pieces and is sold without a prescription. Patients must be instructed to soften the gum and park it between the cheek and gum rather than chew it. Chewing the gum continuously or drinking acidic beverages reduces nicotine absorption. Advantages include rapid absorption of nicotine, with resultant reduction in withdrawal symptoms.

Nicotine patches have the advantage of a delivery system that maintains nicotine levels throughout a longer period than any other system. Patches are designed to deliver nicotine transdermally over a 16- or 24-hour period. The most common side effects are rash and insomnia. Switching from 24-hour to 16-hour release systems can often solve sleep problems associated with longer-release patches. Patients usually use patches at a steady dose daily for 6 to 12 weeks, then taper slowly over an additional 6 to 12 weeks. Nicotine nasal sprays, inhalers, and lozenges are also available.

Non-Nicotine Medications

Bupropion hydrochloride (Zyban) also has demonstrated efficacy in smoking cessation. Bupropion is an atypical antidepressant with noradrenergic and dopaminergic effects. Numerous studies have shown that bupropion therapy, given in the context of a comprehensive smoking cessation program, doubled the number of subjects reporting no nicotine use in the week before the follow-up contact. The recommended and maximum dose of bupropion is 300 mg a day, given as 150 mg twice daily. Dosing should begin at 150 mg a day—given every day for the first 3 days—followed by a dose increase for most patients to the recommended usual dose of 300 mg a day.

Therapy is typically begun 1 to 2 weeks before the patient’s predetermined smoking quit date. Treatment should continue for 12 weeks. Bupropion is contraindicated in those with a seizure disorder, those with anorexia or bulimia, or those who have used a monoamine oxidase inhibitor (e.g., selegiline [Eldepryl], tranylcypromine [Parnate], or phenelzine [Nardil]) within the previous 14 days. Health care providers interested in prescribing bupropion should thoroughly review the manufacturer’s product information before deciding to initiate therapy.

Varenicline was approved by the FDA in 2006 for the treatment of nicotine dependence and is recommended by the treatment guidelines as first-line treatment. This medication appears to represent a partial agonist that binds with high affinity to the neuronal nicotinic acetylcholine receptor. Nicotine stimulation of this particular receptor, with which varenicline binds with high specificity, is associated with significant mesolimbic dopamine release, which serves to reinforce nicotine ingestion. The high affinity with which varenicline binds to this receptor prevents nicotine itself from stimulating the receptor, thereby reducing the reinforcing properties of nicotine ingestion.

In three studies comparing varenicline with buproprion, placebo, or both, varenicline 1 mg twice daily resulted in 52-week continuous abstinence rates of 21% to 23% (95% confidence intervals [CIs] ranging from 17% to 28%), whereas buproprion and placebo produced rates of 14% to 16% (95% CI, 11%-20%) and 4% to 10% (95% CI, 1%-13%), respectively.^1-3 The most commonly reported side effects have been nausea, insomnia, and headache. Disturbing or bizarre dreams have been reported at higher rates than placebo, but these have rarely been so severe as to lead to discontinuation of treatment. The FDA has advised clinicians to monitor patients taking varenicline for changes in behavior, agitation, depressed mood, suicidal thoughts or behavior, and worsening of preexisting psychiatric illnesses.

Alternative therapies for smoking cessation include a wide range of strategies from herbal supplements to laser treatments. Two popular alternative therapies include hypnosis and acupuncture. Currently, both acupuncture and hypnosis should be considered as supplements to well-established treatments rather than first-line recommendations because the research has not been conclusive concerning the effectiveness of these treatments.

Treatment Outcomes

Abstinence Rates

Fully 70% of smokers report wanting to quit, and 46% attempt to quit each year. Only 5% to 7% of them are abstinent from smoking for an entire year after quitting. Several factors appear to affect rates of abstinence in different groups. Women have less success with quitting smoking and higher rates of relapse. Patients with higher levels of nicotine dependence (as evidenced by higher FTND scores) and those with a history of depression also have lower abstinence rates. African Americans and Chinese Americans have lower smoking cessation numbers than European Americans. The primary care provider should consider referring patients in these groups to a more-intensive smoking cessation program and adding nicotine replacement or bupropion (or both) to increase the likelihood of successful abstinence.

Meta-analysis of multiple research studies suggests that intensive counseling programs significantly increase cessation rates. Research suggests that more is better, with more frequent counseling leading to better cessation rates. Bupropion and nicotine gum have been shown to double the rate of abstinence.

Weight Gain

Weight gain is a common problem that can negatively affect rates of successful smoking cessation. Weight gain in patients following smoking cessation can be attributable to replacing the oral nicotine habit with another oral habit: consuming food. Patients undergoing cessation are also likely to be able to taste and smell food better following smoking cessation, which may contribute to overeating. Other mechanisms contributing to weight gain after smoking cessation include increased caloric intake, decreased resting metabolic rate, and decreased physical activity. Estimated average weight gain as a result of smoking cessation is approximately 4 pounds for both men and women.

To help alleviate concerns about gaining weight, health care providers can discuss healthy replacement strategies for nicotine including drinking water, exercising, and eating healthful foods such as raw fruits and vegetables. Many patients also benefit from a discussion of the benefits of quitting smoking versus the risks of the small amount of actual weight gain.

Future Directions

Research on the genetic contributions to nicotine dependence suggest that someday, genetic profiles of smokers may be used by providers to choose the type, duration, and dose of treatments for individual smokers to improve treatment outcomes.

Prevention and Screening

Considering the highly addictive nature of nicotine and the difficulties smokers face in becoming abstinent, perhaps the best approach to reducing smoking rates is to educate the public regarding the dangers of smoking and to prevent exposure to nicotine before an addictive pattern establishes itself. Clinicians can have an effect on the formation of attitudes regarding smoking in young people by clearly explaining the negative health effects and costs of exposure to cigarettes. Health care providers should also consider supporting tobacco control legislation, such as smoke-free laws. Reviewing available practice guidelines such as Treating Tobacco Use and Dependence: 2008 Update by the U.S. Department of Health and Human Services and the American Psychiatric Association’s 2006 Practice Guideline for the Treatment of Patients with Nicotine Dependence can help clinicians stay up to date on the current state of understanding of this significant public health problem.

Summary

Ask every patient about tobacco use.
Engage patients in brief counseling.
Discuss pharmacologic options including nicotine replacement, varenicline, and bupropion therapy.
Consider referral to intensive smoking cessation treatments.

References

Gonzales D, Rennard SI, Nides M, et al: Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47–55.
Jorenby DE, Hays JT, Rigotti NA, et al: Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006;296:56–63.
Tonstad S, TØnneson P, Hajek P, et al: Effect of maintenance therapy with varenicline on smoking cessation: A randomized controlled trial. JAMA 2006;296:64–71.

Cleveland Clinic Smoking Cessation