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Table of Contents

Published November 15, 2005

Kathleen R.
Ashton, PhD

Departments of
Psychiatry and
Psychology

David
Streem, MD

Departments of
Psychiatry and
Psychology

Print Chapter

Definition

Prevalence

Pathophysiology

Signs and
Symptoms

Treatment

Outcomes

References

Fifty-five percent of Americans have tried smoking. Approximately 22.8% of Americans are current smokers and 30% are exsmokers.⁴ The rates of smoking in the general US population decreased from nearly 42% in 1965 to just over 25% in 1990, but the rate of decline has slowed markedly since 1990.^1,5

Nicotine dependence is more prevalent in persons with other mental disorders. According to DSM-IV-TR, 55% to 90% of those with a mental disorder smoke compared with 22% of the general population. There is a high comorbidity of depression with nicotine dependence.⁶ 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.

In the United States, the rates of smoking are decreasing more rapidly for males than for females, although male smokers continue to outnumber female smokers. In 2001, 25.2% of US males and 20.7% of females were smokers.⁴ The incidence of tobacco use is higher in African Americans, in those with less education, and in those of lower socioeconomic status.⁷ 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.⁸ Genes may account for as much as 54% of the variance in failed smoking cessation according to one study.⁹ Risk factors for development of nicotine dependence include a history of alcohol or drug use disorders, primary psychotic disorders (like schizophrenia) and attention-deficit disorders. 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.⁸

Fully 70% of smokers report wanting to quit, and 46% attempt to quit each year.¹⁰ Only 5% to 7% of them are abstinent from smoking for an entire year after quitting.⁶

From the first use of nicotine, physical effects serve to increase the likelihood of repeated nicotine consumption. Nicotine binds to cholinergic receptors in the central nervous system including the anterior nuclei of the thalamus and the cerebral cortex among other areas. In response to repeated nicotine use, the receptors rapidly desensitize and increase in numbers, 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). Nicotine also causes the release of serotonin, beta endorphins, vasopressin, and glutamate. Nonnicotine components of tobacco smoke inhibit the enzymes monoamine oxidase type A (MAO_A) and type B (MAO_B), further increasing neurotransmitter expression. 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 increases. Increasingly desensitized cholinergic receptors on neurons projecting to the NAcc are quickly produced (up-regulated) 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 mailtain 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.

Withdrawal effects occur in about half of smokers trying to quit.⁸

Smoking increases the metabolism of several medications. The effect does not appear to be attributable to nicotine, but rather to a number of other chemicals present in tobacco smoke. By inducing the cytochrome 1A2 hepatic metabolism pathway, the blood levels of the following medications may be lower than expected:

Conversely, the blood levels of these medications may increase when smoking cessation is attempted.

While the pharmacologic effects of nicotine and the other components of tobacco smoke very clearly affect the structures in the brain associated with substance dependence, the behavioral aspects of habitual smoking must not be underestimated. Smokers develop strong associations between smoking and other activities—eg, taking breaks at work, eating, and sexual activity. These associations are stored in neural memory circuits associated with emotional memory (amygdala), reward (nucleus accumbens) and determining priority/importance of elements of one's surroundings (orbitofrontal cortex and cingulate gyrus).¹¹ Resisting the cravings associated with activation of these pathways is often the greatest challenge smokers face when attempting to quit.

The first step in treating nicotine dependence is identifying tobacco users. Clinical guidelines for tobacco dependence treatment suggest asking patients systematically at each visit whether they use tobacco.¹² 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.¹²

The criteria for diagnosis of nicotine dependence follow those for other forms of substance dependence.³ According to the 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:

1. Tolerance—Signs of tolerance are a need for an increased amount of nicotine to produce the desired effect or a diminished effect with continued use of the same amount of nicotine. Nausea and dizziness are not present when using nicotine.
2. Withdrawal (see Table 1).
3. Nicotine is used in larger amounts than intended.
4. The user has a persistent desire or makes unsuccessful attempts to cut down on tobacco.
5. A great deal of time is spent in using the substance (eg, chain smoking).
6. Important social or occupational activities are reduced because of tobacco use.
7. 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.

In addition, smoking may create negative interactions among family members.

Once a diagnosis of nicotine dependence is made, it is useful to characterize the degree to which the patient is physically dependent on smoking. Tthe Fagerstrom Test for Nicotine Dependence(FTND)¹³ (Table 2), can be very 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. However, two of the six questions are weighted to comprise a large portion of a patient's total score. These are:

• "How many cigarettes per day do you smoke?"
• "How soon after you wake up do you smoke your first cigarette?"

In fact, if a patient reports that the total number of cigarettes is greater than thirty and the time after arising before the first morning cigarette is less than five minutes, he or she can be classified as (at least) "highly" nicotine dependent without further questioning.

Psychosocial Interventions and Pharmacologic Options:
Effective smoking cessation treatment essentially starts with each health care provider assessing tobacco status and offering treatment tools and motivation. Smoking status should be queried at each visit by health care providers. The goal of any therapy is to help smokers to quit. Primary care physicians are likely to be most effective in using brief interventions and providing advice and/or prescriptions for pharmacological 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
In smoking cessation research and treatment, psychosocial interventions are often characterized as either "minimal/brief" or "intensive".⁸ Both types of interventions can increase quit attempts and quit success rates to different degrees. A primary care provider may choose to provide either or both types of services in their office settings. "Minimal/brief" interventions require little cost and/or time from the intervener. These would include brief advice in a primary health care provider's office, tailored mailings, or brief telephone counseling. 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.¹⁴ Decision trees (Figure 1) can be helpful in guiding providers through smoking-cessation counseling with patients. By referring patients to local and national resources (Table 3), even providers with limited resources can make a significant difference in educating patients with nicotine dependence.

At the primary care level, national guidelines recommend brief interventions.¹² Interventions as short as 3 minutes may substantially increase cessation rates. One common brief intervention designed for health care providers is the "5 A" method, which involves: (1) asking about tobacco status at each visit, (2) advising all tobacco users to quit, (3) assessing the patient's willingness to quit, (4) assisting the patient in quitting, and (5) arranging for follow-up contact (Table 3). Follow-up contact may consist of a brief visit or phone call 2-3 days after quit date.¹⁴

Providers can assess a patient's readiness to quit using the transtheoretical model of behavior change.¹⁵ If the patient has not thought about quitting, they are in the Precontemplation stage. At this stage, the provider can use motivational interviewing skills to help increase readiness for change¹⁴ (Table 5). When applying motivational interventions, it is important to meet the patient at the patient's level of readiness to be most effective. The goal for a patient who is in "precontemplation" for example, is to start to think about quitting, not quit after the current visit. Health care providers can use the "5 Rs" (Table 5) to help enhance a patient's motivation to quit: (1) discuss why quitting is personally relevant; (2) identify potential risks associated with smoking; (3) identify potential rewards and benefits related to quitting; (4) identify potential barriers or roadblocks that might impede the quitting process; and (5) repeat motivational interventions at each visit. There is some evidence that smoking reduction advice along with offering nicotine replacement and/or buproprion (Zyban) may be an effective strategy for smokers initially unwilling to quit.^16,17 However, in general, patients at this stage are unlikely to benefit from advice-giving as much as a non-threatening discussion of what is keeping them from quitting at this time.

If the patient is considering quitting but not in the next few months, the patient is in the Contemplation stage. The above motivational interventions along with encouragement and education are likely to be beneficial for patients at this stage.

Patients who have made plans to quit are in the Preparation stage. These are the patients who will most benefit from brief interventions. There are some brief techniques that a provider can use to help patients quit:

• Help them identify a "quit date"
• Identify any barriers to quitting for the individual
• Ask them to elicit support from friends and family
• Have patients write down their reasons for quitting or coping strategies
• Discuss removing all tobacco products from their environment
• Encourage patients to eliminate some of their "links" to smoking before quitting, ie, eliminating smoking in the car, on the phone, at work, etc.
• Discuss having patients ask family members to smoke outside while they are trying to quit
• Discuss coping strategies such as replacements (sugar free gum, water) and distraction (keeping busy, exercising)
• If the patient is interested, refer him or her to an intensive smoking cessation counseling program (For information on the CCF Smoking Cessation Program, visit their website).
• Provide patients with advice about nicotine replacement and/or discuss utility of bupropion

Patients in the Action stage (those in the process of quitting) are also likely to benefit from the above brief interventions.

Relapse prevention is important for patients in the Maintenance stage (those who have quit smoking). Providers at this stage can educate individuals 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.

Intensive Behavioral Interventions
Primary care physicians may also choose to refer their patients to intensive counseling programs for smoking cessation. "Intensive" interventions are recommended by national guidelines as effective 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. "Intensive" smoking cessation programs are usually conducted by a clinical nurse specialist, psychologist, chemical dependency counselor, or other healthcare provider with special training or experience in nicotine dependence treatment. Patients are enrolled after assessment of the patient's tobacco use and readiness to change. More intensive programs appear to generate better outcomes. Treatments generally lasts for four or more sessions, of 10 or more minutes each¹². Education regarding pharmacotherapy to supplement the education provided by the primary care physician is usually a part of the program. Research with inpatients supports the use of combining pharmacotherapy and intensive counseling.¹⁸

Intensive counseling and behavioral therapies for smoking cessation may contain the following elements:

• Problem solving/skills training
• Identifying coping strategies for potential relapse situations
• Identifying triggers of smoking/relapse such as situations, events, and people
• Providing psychoeducation about the facts about quitting successfully, nicotine withdrawal, and addiction
• Social support
• Encouragement and reinforcement
• Discussion about the patient's experiences in quitting
• Discussion of both behavioral and pharmacological coping strategies for withdrawal

Intensive programs help patients cope with nicotine withdrawal through a number of behavioral strategies. Patients benefit from social support within a group-discussing withdrawal can help the patient cope with the emotional effects. Many intensive programs also offer cognitive strategies to cope with withdrawal such as developing coping phrases (eg, "One day at a time"). Intensive programs may offer training in relaxation strategies, such as diaphragmatic breathing, which can counteract both physical and emotional withdrawal symptoms.

Pharmacological Interventions
National guidelines recommend that pharmacologic therapy be considered for all smokers attempting to quit unless medically contraindicated.¹² Pharmacologic interventions include nicotine replacement strategies and antidepressant treatment.

Nicotine replacement therapies (NRTs) include transdermal nicotine patches, gums, nasal spray, lozenges, and inhalers. Both transdermal nicotine patches and nicotine gum are available without prescription. Nicotine replacement options 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 half 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. The advantages of NRT include rapid onset of action, a wide variety of delivery mechanisms, and a step-down approach that allows the patient to gradually decrease nicotine intake over time and minimize withdrawal symptoms.

NRT has potential disadvantages as well. Patients can become dependent on nicotine replacement systems (although the likelihood of this is low).¹⁹ In addition, it is possible for patients to focus too much of their smoking cessation program on nicotine replacement, while neglecting social and behavioral reinforcers of their addiction. As a result, when the NRT is discontinued they find themselves unable to tolerate cravings cued by behaviors, places and even sensations (eg, encountering the aroma of tobacco in a place he/she associated with smoking or finding a forgotten favorite lighter). Because of these behavioral and cognitive aspects of nicotine addiction, behavioral counseling (either brief or intensive) is an important adjunct to any pharmacological intervention for smoking cessation.

Nicotine Gum and Patch
Nicotine gum is a product that releases nicotine for absorption into the buccal mucosa. It 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 against the buccal mucosa rather than chewing it. Chewing the gum continuously or drinking acidic beverages will reduce nicotine absorption. The vast majority of patients tolerate nicotine gum quite well. Patient acceptance of the taste of these products varies. 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 6-12 weeks, then taper slowly over an additional 6-12 weeks. Patients may combine the sustained-release properties of a nicotine patch with the rapid-absorption effects of nicotine gum during high-risk situations. This approach may increase abstinence rates by 5-10%.⁸

Nicotine Nasal Sprays, Iinhalers and Llozenges
Nicotine nasal sprays, inhalers, and lozenges are also available. These delivery systems seem to have similar pharmacokinetics and similar applications as nicotine gum. That is, they all produce a rapid absorption of nicotine and may benefit patients in high-risk situations. By virtue of its design, nicotine inhalers may also serve as a behavioral replacement for smoking. Lozenges come in 2 mg and 4 mg dosages (just like nicotine gum) and are taken sublingually. Absorption is essentially the same as nicotine gum. Some patients who have difficulty using nicotine gum may have more success with lozenges.

Bupropion hydrochloride (Zyban)
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 buproprion therapy, given in the context of a comprehensive smoking cessation program, doubled the number of subjects reporting no nicotine use in the week prior to the follow-up contact. According to the GlaxoSmithKline package insert information,

"The recommended and maximum dose of Zyban is 300 mg/day, given as 150 mg twice daily. Dosing should begin at 150 mg/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/day"

Doses should be separated by at least eight hours between successive doses, and each dose should be taken whole (not crushed, divided or chewed). Therapy is begun before the patient's predetermined smoking quit date. It takes about seven days for steady-state blood levels of buproprion to be attained, so the quit date is typically 1-2 weeks after Zyban is initiated. Treatment should be continued for twelve weeks. The most commonly reported side effects are insomnia, bronchitis, dry mouth, and numbness. Its use is contraindicated in those with a seizure disorder, those with anorexia/bulimia, or those who have used a monoamine oxidase inhibitor (eg, selegiline (Eldepryl), tranylcypromine (Parnate), or phenelzine (Nardil)) within the previous 14 days. Some research suggests that the combination of nicotine replacement and bupropion may have additional benefits in quitting.¹⁶ Health care providers interested in prescribing Zyban should thoroughly review the manufacturer's product information before deciding to initiate therapy.

Nortriptyline (Pamelor), a tricyclic antidepressant, has also been studied as a potential aid in helping smokers quit.²⁰ While some studies suggest nortriptyline may be equally effective as buproprion SR, the poorer tolerability and increased rate of adverse cardiovascular effects have limited the practical utility of this agent. Nortriptyline is not an FDA-approved treatment for nicotine dependence. In patients for whom buproprion SR is contraindicated, though, nortriptyline may be considered.

In the Cleveland Clinic Foundation’s Smash the Ash program, we tend to recommend buproprion and the nicotine replacement patch (along with behavioral counseling) above other pharmacological treatments because of their utility for managing withdrawal symptoms while dissociating the links of nicotine with other habits and behaviors.

Addressing Weight Gain Concerns
Weight gain is a common problem that can negatively impact 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 weight gain. Other mechanisms contributing to weight gain after smoking cessation include increased caloric intake, decreased resting metabolic rate, and decreased physical activity.²¹ Changes in adipose tissue metabolism and lipoprotein lipase activity during smoking cessation may also lead to weight gain. Neuropeptides and peptide hormones like leptin and neuropeptide Y have effects on food intake and nicotine (or other components of tobacco smoke) may alter activity of these molecules. Monoamines like norepinephrine, dopamine and serotonin clearly have effects on appetite, and nicotine definitely changes monoamine activity. Some studies have suggested a relationship between smoking and insulin sensitivity. Some have theorized that weight gain may contribute to a lower rate of successful smoking cessation in women, although there is no actual scientific data supporting this.²¹ Estimated average weight gain due to smoking cessation is approximately four pounds for both men and women.¹⁰

To help alleviate weight gain concerns, providers can discuss healthy replacement strategies for nicotine including drinking water, exercising and eating healthy 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. Emphasizing that quitting has other appearance-related benefits including reduced wrinkles, increased skin quality, and whiter teeth may also motivate patients who are conscious of their self-image.

Alternative Therapies
There are literally hundreds of alternative therapies for smoking cessation including everything from herbal supplements to laser treatments. Two popular alternative therapies include hypnosis and acupuncture. Although some recent research suggests that acupuncture is superior to a placebo control, ^22,23 other researchers have not found promising results.^24,25 One metanalytic study suggested a small benefit of hypnosis over an education-only control.²⁵ However, studies looking at the effectiveness of hypnosis suggest a high amount of variability, with quit rates ranging from 4 to 90%.³⁰ More research is needed to clarify the utility of both acupuncture and hypnosis in smoking cessation. Currently, both acupuncture and hypnosis should be considered as supplements to well-established treatments rather than first line recommendations. In the CCF program, we find self-hypnosis a useful adjunct to our intensive counseling program in managing withdrawal symptoms and teaching the effectiveness of relaxation as a coping strategy.

Several factors appear to affect rates of abstinence in different groups. Women have less success quitting smoking and higher rates of relapse.⁶ Patients with higher levels of nicotine dependence (as evidenced by higher FTND scores) and those with a history of depression also suffer lower abstinence rates.⁶ African-Americans and Chinese-Americans appear to metabolize nicotine more slowly than Euro-Americans and this may be related to lower smoking cessation numbers in these groups as compared to Euro-Americans.⁷ The primary care provider should consider referring patients in these groups to a more intensive smoking cessation program and adding nicotine replacement or buproprion SR (or both) to increase the likelihood of successful abstinence.

Buproprion and nicotine gum have been shown to not only double the rate of abstinence; in addition, both interventions appear to attenuate cessation-related weight gain.²¹ Unfortunately, these benefits may wane after the therapy is discontinued. It is therefore important to use this time to encourage patients to establish other healthy habits such as diet and exercise.

Meta-analysis of multiple research studies suggests that intensive counseling programs significantly increase cessation rates.²⁰ Research suggests that "more is better," with more frequent counseling leading to better cessation rates.²⁷ In 2006, the American Psychiatric Association is expected to release its updated practice guidelines for substance use disorders, including nicotine dependence. This document will discuss recent scientific and product developments, and should help us in helping our patient abstain from this very harmful and costly behavior.

Return to Medicine Index

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