The FDA recommends that (a) patients tell their healthcare providers about any

history of psychiatric illness before starting varenicline, and (b) clinicians and

patients monitor for changes in mood and behavior during treatment with

varenicline.

69 A large, randomized, controlled trial that included a cohort of smokers

with current or past psychiatric disorders evaluated the neuropsychiatric safety of

varenicline, bupropion, nicotine patch, and placebo. No difference in

neuropsychiatric adverse events was reported between groups.

70 Additionally, a

review of published cases and clinical trials using varenicline in patients with

schizophrenia and schizoaffective disorder concluded that psychiatric symptoms

were not worsened significantly in stable, carefully monitored patients with these

conditions.

71 The prescribing information for varenicline was revised to include

warning for a possible increased risk of cardiovascular events (MI, ischemic and

hemorrhagic stroke) in patients with stable cardiovascular disease.

69 However, a

published meta-analyses examining the risk concluded that there is no significant

increase in the risk of serious cardiovascular events with varenicline in tobacco

cessation.

72 Seizures have been reported in patients treated with varenicline, most

often within the first month of therapy. These events occurred in individuals who had

no seizure history, as well as in those with a remote history or well-controlled

seizure disorder.

69

PRODUCT SELECTION CONSIDERATIONS

Varenicline is a first-line agent for the treatment of tobacco use and dependence.

7,23

It

offers a convenient oral dosing regimen and a new mechanism of action that might be

particularly appealing for patients who have failed quit attempts with other first-line

agents (e.g., NRT or sustained-release bupropion). Given its potential for inducing

negative neuropsychiatric effects, varenicline should be used with extreme caution in

patients with a current or past history of psychiatric illness.

P.J. has tried the nicotine gum and transdermal patch during previous quit attempts.

Because he was intolerant to the nicotine gum (sore jaw), this form of NRT is not

appropriate. P.J.’s experience with the transdermal patch suggests he may benefit

from a short-acting NRT formulation that enables active administration and titration

of drug as needed to alleviate symptoms of withdrawal and situational cravings.

Other first-line therapies include the nicotine nasal spray, inhaler, and lozenge;

sustained-release bupropion; or varenicline. P.J. should not use the nicotine nasal

spray because he has allergic rhinitis and may be more susceptible to the irritant

effects of the spray. In addition, some data suggest that the bioavailability of nicotine

is reduced in patients with rhinitis.

63 Furthermore, the safety and efficacy of the nasal

spray in patients with chronic nasal disorders have not been adequately studied.

Reasonable choices for P.J. therefore include sustained-release bupropion, nicotine

lozenge, nicotine inhaler, or varenicline. Any of these options are reasonable, and the

choice of therapy should be dictated by P.J.’s individual preference. If varenicline is

chosen, given P.J. has underlying cardiovascular disease, he should be instructed to

notify a healthcare provider for new or worsening cardiovascular symptoms and to

seek immediate medical attention if he experiences signs and symptoms of

myocardial infarction. Finally, it is reasonable to consider combination therapy (see

Case 91-3, Question 1).

p. 1920

p. 1921

Safety of Nicotine Replacement Therapy Among

Patients with Cardiovascular Disease

CASE 91-2, QUESTION 4: P.J. would like to try the nicotine inhaler. Is NRT safe for use in patients with

cardiovascular disease?

Nicotine activates the sympathetic nervous system, leading to an increase in heart

rate, blood pressure, and myocardial contractility. Nicotine also may cause coronary

artery vasoconstriction.

74 These known hemodynamic effects of nicotine have led to

doubts about the safety of using NRT in patients with established cardiovascular

disease, particularly those with serious arrhythmias, unstable angina, or recent MI.

Soon after the nicotine patch was approved, anecdotal case reports in the lay press

linked NRT (patch and gum) with adverse cardiovascular events (i.e., arrhythmias,

MI, stroke). Since then, several randomized, controlled trials have evaluated the

safety of NRT in patients with cardiovascular disease.

75–77 The results of these trials

suggest no significant increase in the incidence of cardiovascular events or mortality

among patients receiving the nicotine patch when compared with placebo. However,

because these trials specifically excluded patients with unstable angina, serious

arrhythmias, and recent MI, the manufacturers of NRT products recommend that these

agents be used with caution among patients in the immediate (within 2 weeks) postMI period, those with serious arrhythmias, and those with unstable angina.

7

Although two small, retrospective studies have raised questions regarding the

safety of NRT use in intensive care settings,

77,78 NRT use in patients with

cardiovascular disease has been the subject of numerous reviews, and it is widely

believed by experts in the field that the risks of NRT in this patient population are

small in relation to the risks of continued tobacco use.

2,53,72,74,75 The 2008 Clinical

Practice Guideline concludes that there is no evidence of increased cardiovascular

risk with these medications.

7 Although the use of NRT may pose some theoretic risk

in a patient like P.J., cigarette smoking is far more hazardous to his health. Cigarettes,

unlike NRT, deliver numerous toxins that induce a hypercoagulable state, reduce the

oxygen-carrying capacity of hemoglobin, and adversely affect serum lipids. The

amount of nicotine that P.J. would receive using the recommended dose of any NRT

product will not exceed the amount he previously obtained from his 2 PPD smoking

habit. The clinician should strongly encourage pharmacotherapy during P.J.’s current

quit attempt. P.J. is 10 lb overweight; the additional risk imposed by a modest weight

gain after smoking cessation likely will not be of clinical significance compared with

that of continued smoking.

Combination Therapy for Tobacco Dependence

CASE 91-3

QUESTION 1: J.B. is a 60-year-old man referred to the pulmonary clinic for further evaluation and

management of his chronic obstructive pulmonary disease (COPD). He complains of decreased exercise

tolerance and has noted increasing shortness of breath (SOB) with minimal exertion (e.g., while golfing or

climbing stairs). He currently uses an albuterol inhaler (90 mcg/puff), 2 puffs every 4 hours regularly for SOB.

His medical history is otherwise unremarkable except for osteoarthritis controlled with acetaminophen 1 g TID.

He has smoked approximately 1.5 to 2 PPD for more than 40 years. J.B. indicates he has made several quit

attempts during the past year. On the first attempt (quitting “cold turkey”), J.B. relapsed within 2 days. J.B.

successfully quit for nearly 2 weeks on his second attempt (using the 4-mg nicotine lozenge), but he found it

difficult to adhere to the frequent dosing schedule and relapsed shortly after discontinuing the lozenge. His most

recent quit attempt was 6 months ago using varenicline. After 1 month of abstinence, J.B. self-terminated

varenicline (I thought I didn’t need it anymore) and relapsed within 1 week. On further questioning, J.B. states

that he did not enroll in a behavioral counseling program or seek additional assistance (other than

pharmacotherapy) during any of his quit attempts. He expresses an interest in smoking cessation but is

discouraged by his prior lack of success. On physical examination, coarse breath sounds that clear after

coughing are noted. A chest radiograph obtained in the office shows no infiltrates. J.B. is concerned about his

worsening pulmonary function and is committed to making another effort to quit. What treatment options are

appropriate for J.B.?

Tobacco smoking is the single most important risk factor for the development of

COPD,

3 and nearly all patients diagnosed with COPD are current or former

smokers.

79 Given his escalating pulmonary symptoms, it is imperative that he stop

smoking as soon as possible. J.B. should be advised that medications for COPD offer

only limited symptomatic relief, and the most important component of his treatment is

smoking cessation.

79,80 The clinician should commend J.B. for his interest in quitting

and help him devise a patient-specific treatment plan.

Plasma levels of nicotine achieved with standard doses of NRT are generally

much lower than those attained with regular smoking.

63,81 As such, conventionally

dosed NRT may deliver subtherapeutic nicotine levels for some individuals, and in

particular, for moderate-to-heavy smokers.

Combination NRT regimens, which typically consist of a long-acting agent

(nicotine patch) in combination with a short-acting formulation (i.e., gum, lozenge,

inhaler, or nasal spray), are often used as initial therapy. The long-acting formulation,

which delivers nicotine at a relatively constant level, is used to prevent the onset of

severe withdrawal symptoms, and the short-acting formulation, which delivers

nicotine at a more rapid rate, is used as needed to control withdrawal symptoms that

may occur during potential relapse situations (e.g., after meals, during times of stress,

when around other smokers).

Controlled trials suggest that the nicotine patch in combination with short-acting

NRT formulations (i.e., gum, lozenge, nasal spray, or inhaler) significantly increase

quit rates relative to placebo. Similar results have been observed in trials using

combination therapy with sustained-release bupropion and the nicotine patch.

Aggressive combination regimens including triple-agent NRT (e.g., patch, inhaler,

and nasal spray) with or without sustained-release bupropion, triple-combination

therapy (e.g., patch, inhaler, and sustained-release bupropion)

82 may be a safe and

effective treatment approach. Some data suggest that adding varenicline alone

83 or

sustained-release bupropion and varenicline to nicotine patch,

84,85

therapy may

improve cessation rates; however, addition of bupropion sustained-release to

varenicline had little effect on long-term abstinence and increased rates of

depression and anxiety.

85

Clinicians should be aware that although the combination of the nicotine patch and

sustained-release bupropion has been approved by the FDA, the concurrent use of

multiple NRT products is not FDA-approved for tobacco cessation. Furthermore, the

optimal agents, dosages, and durations of therapy for NRT combination therapy are

currently unknown.

Given the severity of J.B.’s condition and his willingness to quit now, the clinician

should initiate treatment as soon as possible. His treatment should consist of

pharmacotherapy in conjunction with behavioral counseling and appropriate followup.

p. 1921

p. 1922

PHARMACOTHERAPY

The clinician should work with J.B. to select the most appropriate pharmacotherapy.

As noted previously, appropriate options would include the various NRT

formulations, sustained-release bupropion, varenicline, or an effective combination

of first-line agents. For patients reporting a positive experience with a given

medication, retreatment with the same agent or a combination of agents might be

appropriate, with consideration given to increasing the dose, frequency, or duration

of therapy. For patients reporting a negative experience with pharmacotherapy (e.g.,

poor adherence, side effects, palatability issues, cost), an alternative agent should be

considered. Given J.B.’s previous adherence issues with the nicotine lozenge as

monotherapy, it might be preferable to use a long-acting cessation medication such as

the nicotine patch, sustained-release bupropion, or varenicline. Combination therapy

might also be appropriate.

BEHAVIORAL COUNSELING

Although medications are effective alone in helping patients quit smoking, the

combination with pharmacotherapy maximizes patients’ chances for a long-term,

successful quit attempt. J.B.’s previous 1-month-long quit attempt highlights the

success of varenicline in this patient; however, J.B.’s relapse likely is attributable to

a shortened course of therapy and the absence of a behavioral change program. J.B.

should be advised that the medications are designed to make patients more

comfortable while quitting and that behavioral counseling is needed to address the

“habit” of smoking by helping him cope with difficult situations and triggers for

relapse. J.B. should be advised to JB should be advised to pursue behavioral therapy

options in addition to pharmacotherapy. J.B. should be reminded that adherence with

the medication regimen—daily adherence, as well as duration of therapy—will

increase his chances of quitting for good. Clinician-delivered counseling might also

include a personalized message to further enhance his motivation to quit. For

example, the clinician could perform pulmonary function testing and translate J.B.’s

spirometry results into an effective “lung age” (e.g., the age of the average healthy

individual with similar spirometry values). This educational approach has been

found to significantly increase long-term (12-month) quit rates in a recent controlled

trial.

86

Drug Interactions with Smoking

CASE 91-4

QUESTION 1: M.K. is a new patient requesting Ortho Cyclen (norgestimate/ethinyl estradiol). The new

patient history form completed by M.K. reveals that she is 32 years old, weighs 65 kg, and is 70 inches tall. She

takes no prescription medications but occasionally uses loratadine 10 mg as needed for allergies, and ibuprofen

400 mg as needed for dysmenorrhea. She has no significant medical history. Her father has hypertension and

suffered an MI last year. Her mother has type 2 diabetes and dyslipidemia. Her social history is significant for

tobacco use (1 PPD for 15 years), alcohol (1 glass of wine/night), and caffeine (3–4 cups of coffee daily). Are

there any potential drug interactions with M.K.’s new prescription?

SMOKING AND COMBINED HORMONAL CONTRACEPTIVES

One of the most important precautions to consider with oral contraceptive use is the

potential interaction between tobacco smoke and estrogens in combination hormonal

contraceptives (see Chapter 47, Contraception). Estrogens are known to promote

coagulation by altering clotting factor levels and increasing platelet aggregation. As

described in Case 91-2, Question 1, substances present in tobacco smoke induce a

hypercoagulable state, increasing the risk of acute cardiovascular events. Exposure to

both factors (smoking and high levels of estrogen) greatly increases the risk of

thromboembolic and thrombotic disorders. Considerable epidemiologic evidence

indicates that cigarette smoking substantially increases the risk of adverse

cardiovascular events, including stroke, MI, and thromboembolism in women who

use oral combination hormonal contraceptive agents.

87,88 This risk is age-related, in

that the absolute risk of death as a result of cardiovascular disease in oral

contraceptive users who smoke is 3.3/100,000 women ages 15 to 34 years compared

with 29.4/100,000 women ages 35 to 44 years. To put this in perspective, the

corresponding risk of death as a result of cardiovascular disease in nonsmoking

women who use oral contraceptives is much lower, with a death rate of 0.65/100,000

women ages 15 to 34 years and 6.21/100,000 women ages 35 to 44 years.

89 Because

of the increased risk of adverse cardiovascular events, current guidelines

89 state that

combination estrogen–progestin contraceptives should not be used in women who are

older than 35 years of age and smoke, and progestin-only or nonhormonal

contraceptives are recommended for use in this population. M.K. is 32 years of age,

and despite smoking 20 cigarettes/day, oral contraceptive use is not contraindicated

at this time. However, the clinician should strongly advise M.K. to quit smoking and

assess her readiness to do so. M.K. should be informed that if she continues to smoke

while using oral combined hormonal contraceptives, her risk of developing a blood

clot, stroke, or heart attack will continue to increase with time.

ALTERNATIVE THERAPIES

CASE 91-4, QUESTION 2: M.K. asks whether e-cigarettes or vapes are effective for smoking cessation.

Some patients or clinicians may ask about the efficacy of electronic nicotine

delivery systems (ENDS) in tobacco cessation. These devices seem to offer an

attractive solution in that they may eliminate exposure to the toxic substances inhaled

when tobacco is burned in cigarettes. Little data are available to support use of

ENDS as a tobacco-cessation therapy. A systematic review concluded that ENDS

may help smokers successfully stop smoking, although more robust data on the safety

and efficacy of ENDS are needed.

90 Preliminary data suggest that adding ENDS use

to cigarettes does not increase cessation.

91 Data are unclear on the safety of ENDS as

a cessation method, although to date few adverse events have been reported.

90, 91

M.K. should be advised that the efficacy of ENDS as cessation therapies is not well

established, and use of these agents cannot be recommended at this time.

Although many herbal and homeopathic products are available to help people quit

smoking, data that support their safety and efficacy are lacking. Furthermore, patients

should be cautioned that herbal cigarettes are not safe alternatives because they result

in the inhalation of other toxins present in smoke.

CASE 91-4, QUESTION 3: M.K. is not considering quitting smoking in the next 30 days. She cannot

discontinue her oral contraceptives because she is sexually active and needs a reliable form of birth control. She

wonders whether the new low-dose birth control pills or other formulations (e.g., patch, vaginal ring) are safer

for smokers.

Combined oral contraceptives available in the United States contain estrogen in

doses ranging from 20 to 50 mcg of ethinyl estradiol. Higher doses of ethinyl

estradiol appear to have greater procoagulant effects.

92–94

In 2001, the US Surgeon General stated that lower-dose oral contraceptives may

be associated with a reduced risk for coronary

p. 1922

p. 1923

heart disease (CHD) compared with higher-dose formulations. Despite this

conclusion, the report cautioned that heavy smokers who use oral contraceptives still

have a greatly elevated risk for CHD.

94

Serum estrogen levels obtained with the vaginal ring are significantly lower than

those achieved with either transdermal or oral combined contraceptive formulations,

and data have not shown the patch or the ring to be safer options for women who

smoke. Current guidelines apply the same precautions to all contraceptives

containing estrogen.

89

M.K.’s prescribed oral contraceptive agent (Ortho Tri-Cyclen) contains 35 mcg of

ethinyl estradiol in combination with 0.25 mg norgestimate. Although some clinicians

recommend the use of low-dose (20 mcg) estrogen preparations in smokers, the

available evidence suggests that the prescribed regimen poses no additional risk in

M.K. The clinician should inform M.K. that there are currently no studies

demonstrating a reduced risk of adverse cardiovascular events in smokers using oral

contraceptives containing low doses (e.g., 20 mcg) of estrogen or the newer

transdermal and vaginal ring formulations.

95

In the absence of published data, only

smoking cessation can be advocated to definitively reduce the risk of stroke, MI, and

thromboembolism in women who use combined hormonal contraceptives.

BEHAVIORAL COUNSELING

Although M.K. is not considering quitting at this time, it is appropriate for the

clinician to apply the 5 R’s (Table 91-2) to promote motivation to quit. This

counseling should be relevant to M.K.’s situation and should highlight the risks of

continued tobacco use, such as her elevated risk for thromboembolic and thrombotic

disorders (associated with continued use of oral contraceptives). M.K. should be

asked to think about the rewards of quitting and any potential roadblocks to quitting.

At subsequent encounters, the clinician should sensitively assess M.K.’s tobacco use

status and motivation to quit, and offer assistance with quitting when M.K. is ready. If

M.K. decides to quit, it would be important to reassess her caffeine intake because

caffeine, which is metabolized via CYP450 1A, levels have been reported to

increase by 56% in patients who quit smoking.

21

Brief Interventions to Promote Tobacco Cessation

CASE 91-5

QUESTION 1: J.C. is a 52-year-old man with a history of asthma requesting a refill of his albuterol inhaler

prescription. This is the third request for an albuterol inhaler (200 doses/inhaler) during the past 2 months.

Before this period, his last refill was more than a year ago. J.C. reports that he has been using albuterol on most

days of the week for coughing and SOB. He has no other medical conditions and takes no other medications.

His social history is significant for tobacco use (smokes 1.5 PPD; he recently started smoking again after

starting a new job where “everyone smokes”). J.C. previously quit smoking 20 years ago using the “cold

turkey” approach (e.g., no medications or counseling), and although he was successful, he was miserable for

weeks and he expresses reluctance to “go through this again” during a stressful job transition.

The clinician is running behind schedule and does not have the time to provide comprehensive smokingcessation counseling during this patient encounter. What brief smoking-cessation interventions can the clinician

provide to J.C. to assist him with quitting?

TELEPHONE QUITLINES

Clinicians should become aware of local, community-based resources for tobacco

cessation, including telephone quitlines. When time or expertise does not afford

provision of comprehensive tobacco-cessation counseling during a patient visit,

clinicians are encouraged to apply a truncated 5 A’s model, whereby they ask about

tobacco use, advise tobacco users to quit, and refer patients who are ready to quit to

a telephone quitline. Effective brief interventions can generally be accomplished in

fewer than 3 minutes. Telephone services provide low-cost interventions that can

reach patients who might otherwise have limited access to medical treatment because

of geographic location or lack of insurance or financial resources. Data support the

efficacy of quitline counseling in promoting abstinence.

30,32 The addition of

medication to quitline counseling significantly improves abstinence rates compared

with medication alone.

7

In addition, preliminary evidence suggests that quitlines are

also effective for smokeless tobacco cessation.

96 The telephone number for the tollfree tobacco quitline is 1-800-QUIT NOW.

J.C.’s asthma is not well controlled (e.g., increased use of short-acting

bronchodilator). The change in J.C.’s asthma control is temporally related to his

recent job change and relapse to daily smoking. Exposure to tobacco smoke is a

potent trigger for asthma exacerbations and an important cause of poor asthma

control. Given that the clinician is unable to provide comprehensive smokingcessation counseling at this time, a brief intervention is appropriate. The clinician

should strongly advise J.C. to quit as a key component of his asthma management plan

and refer him to a telephone quitline or to other resources that are available within

the community (e.g., local individual or group counseling programs). The clinician

should briefly explain that pharmacologic treatment combined with support should

increase the likelihood of a successful quit attempt compared to his previous, “cold

turkey” experience. clinician could address J.C.’s previous negative experience with

quitting by educating on the benefits of medications in reducing nicotine withdrawal

symptoms.

Smoking Among Individuals with Mental Illness

CASE 91-6

QUESTION 1: J.D. is a 42-year-old woman presenting to clinic for follow-up of her depression management.

Nine months ago, she was started on venlafaxine XR 75 mg daily. At her 3-month follow-up visit, she was

stable on venlafaxine XR 150 mg daily, and her depressive symptoms had improved. She also reported that she

was sleeping much better. J.D. has no other significant past medical history, and she takes no other

medications. Her social history is positive for current tobacco use (1 PPD for 25 years) and caffeine use (1–2

Diet Cokes a day). She does not drink alcohol. During the appointment, J.D. indicates that she would like to quit

smoking because her depression is better, and she knows that her overall health will improve if she quits. She

also states that the last time she attempted to quit (several years ago, using the nicotine gum), she felt “down

and had difficulty concentrating and couldn’t sleep.” She is now fearful that her depression will return if she

quits. Is smoking cessation appropriate for J.D. at this time, and what are her treatment options?

Although persons with mental illness constitute 20% of the US population, nearly

36% smoke cigarettes.

9

In the past, the mental health community has not addressed

smoking cessation with their patients, but increasing evidence suggests that quitting is

possible and should be promoted. For patients with mental

p. 1923

p. 1924

illness to achieve wellness, smoking-cessation intervention is an essential

component of the overall care plan.

97

Given that J.D. is currently willing to quit, and her depression has been stabilized

for more than 4 months, it is appropriate for the clinician to discuss a quitting plan

with J.D. and initiate therapy. The therapeutic approach should include counseling

and pharmacotherapy, with ongoing monitoring of progress toward quitting and

depressive symptoms.

TREATMENT SELECTION

Pharmacotherapy

Because no contraindications are present, any of the FDA-approved medications for

cessation are appropriate. Although data are mixed on efficacy of varenicline in

patients with psychiatric illness,

98 varenicline seems to be safe. In a pooled analysis

of patients without psychiatric disorders, only sleep disorders and disturbances

exhibited a higher incidence in patients treated with varenicline.

98

Regardless of whether sustained-release bupropion, varenicline, or NRT

product(s) are selected, the clinician should monitor J.D. closely to assess incidence

of depressive symptomatology. If sustained-release bupropion or varenicline is

selected, J.D. should be advised to stop taking the medication and contact the

clinician immediately if she experiences agitation, depressed mood, and any changes

in behavior that are not typical of nicotine withdrawal, or if she experiences suicidal

thoughts or behavior.

BEHAVIORAL COUNSELING

Because J.D. has indicated that she is ready to quit, the clinician should commend her

for making the important decision that will positively impact her overall health. J.D.

should be advised that quitting is a process, and it will be important for them to work

closely together to address the physiologic as well as psychological aspects of

quitting during the upcoming months.

CASE 91-6, QUESTION 2: After discussing the various treatment options with the clinician, J.D. decides

that she would like to add sustained-release bupropion to her regimen because the nicotine gum by itself did not

help her much last time. She also thinks that the combination of venlafaxine with bupropion might help to “keep

her depression more stable” whereas she is quitting. She confides in the clinician that her biggest fear is the

ability to avoid smoking when she is stressed because of her job. She is a survey researcher and must meet

client-induced deadlines. How can J.D. cope with stressfulsituations?

A variety of coping mechanisms can be applied to alleviate the need to smoke

during stressful situations or when exposed to other triggers for smoking (Table 91-

3). The clinician should encourage J.D. to think about strategies that would be

effective for her in these situations, such as deep breathing or calling a supportive

friend. Additionally, the clinician should consider suggesting use of a short-acting

NRT product (e.g., nicotine gum, lozenge, inhaler, or nasal spray) as needed to

alleviate situational cravings to smoke. Appropriate dosing of sustained-release

bupropion should be reviewed (Table 91-4). A follow-up appointment should be

scheduled for approximately 3 months after the quit date, and the patient should be

advised to contact the clinician if she encounters any difficulties before then.

CASE 91-6, QUESTION 3: Four weeks later, J.D. calls and reports that she has a dry mouth, is having

difficulty sleeping, and feels jittery and anxious. She also is currently using nicotine gum (2 mg), approximately

four pieces daily. How should J.D. be managed?

As noted above, insomnia and dry mouth are commonly associated with sustainedrelease bupropion therapy and usually lessen with continued use.

67 The nicotine gum

dose is low and not likely contributing to this condition. To address insomnia, J.D.

can be advised to take the second dose of the day earlier, but not less than 8 hours

after the first dose of the day. Alternatively, the clinician could consider reducing the

daily dose to 150 mg in the morning and omitting the evening dose. Although the

manufacturer recommends 300 mg/day, the 150-mg dose has been shown to have

comparable outcomes with those of the 300-mg dose and is better tolerated.

99, 100 The

clinician also should assess J.D.’s caffeine consumption patterns and, if appropriate,

suggest that she reduce her caffeine intake by 50% and not drink caffeinated

beverages after 12 noon so her system is clear of its stimulatory properties before

sleep.

22

Extended-Use Medications for Cessation

CASE 91-6, QUESTION 4: J.D. returns to the clinician’s office 3 months later and indicates that she is doing

well but had a few “slips” and smoked four times. She has not felt depressed and has been handling her stress

at work through deep-breathing exercises. She uses the nicotine gum a few times a week and does not feel

ready to discontinue the sustained-release bupropion. She wonders whether it is possible to continue the therapy

for a bit longer, untilshe feels more stable as a nonsmoker.

Extended-duration medication therapy appears to be safe and effective. Long-term

follow-up data indicate that approximately 15% of long-term quitters continued

nicotine gum therapy with no serious side effects.

101 The 2008 Clinical Practice

Guideline states that extended use of medications might be beneficial in individuals

who report persistent withdrawal symptoms during treatment, those who have

relapsed shortly after medication discontinuation, or those who are interested in

long-term therapy.

7

Clinicians should be aware that although many of the medications (sustainedrelease bupropion, varenicline, nicotine nasal spray, and inhaler) are approved by

the FDA for long-term (6-month) use, the effectiveness of additional weeks on

therapy is not well established. A meta-analysis of eight trials found that extended

treatment with varenicline might prevent relapse, extended treatment with bupropion

is unlikely to have a clinically important effect, and studies of extended treatment

with nicotine replacement are needed.

102 Given J.D.’s current depression and

because she is interested in continuing therapy, it is reasonable for the clinician to

recommend continuation of therapy for an additional 12 weeks and reassess progress

at that time. If JD does decide to discontinue her bupropion, then it should be with

close monitoring by her mental health professional to assess for any rebound

depressive symptoms.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Benowitz NL. Nicotine addiction. N EnglJ Med. 2010;362(24):2295. (19)

Benowitz NL et al. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol. 2009;

(192):29. (22)

p. 1924

p. 1925