American College of Physicians: Internal Medicine — Doctors for Adults ®


With smoking cessation drugs, dosing is key

From the April ACP-ASIM Observer, copyright 2002 by the American College of Physicians-American Society of Internal Medicine.

By Gina Rollins

Second-line therapies for smoking cessation
How you can convince patients it's time to quit

When it comes to smoking cessation, the statistics can be disheartening. Nearly a quarter of all U.S. adults smoke, and nearly two-thirds of them want to quit.

But while about half try to kick the habit each year, only about 7% who try to stop on their own do so for good. Just as depressing, those who eventually quit typically try between five and seven times.

What you may not know, however, is how cigarettes deliver nicotine and how you can best prescribe commonly available drug therapies to mimic that delivery system. Over the years, experts have learned some valuable lessons about how to make the most of drug therapies for smoking cessation.

While counseling and behavioral therapy are important strategies to help patients stop smoking, many experts say nearly all of them will need help in the form of drug therapy. By using the right drug doses and combining therapies, they say, you can take some concrete steps to help patients quit for good.

The right dose

The FDA has approved five first-line drug therapies to treat tobacco dependence. Four involve nicotine replacement, including transdermal patches, gum, vapor inhalers and nasal sprays. The fifth, sustained-release bupropion (Zyban), is a monocyclic antidepressant.

Nicotine patches are now available as an over-the-counter (OTC) drug only. Nicotine nasal sprays and inhalers are prescription-only; gum is OTC-only.

According to U.S. Public Health Service guidelines, nicotine gum improves long-term abstinence rates by approximately 30% to 80% over placebo. The patch improves those rates between 70% and 120%. Far fewer studies of the inhaler and nasal spray have been done, but meta-analyses of studies on both products indicate they offer double the cessation rates of placebo.

There are no hard-and-fast rules about which medication will work best for individual patients. The key, however, is to make sure your patient gets enough nicotine.

"Underdosing is not uncommon," explained Richard D. Hurt, FACP, director of the Mayo Clinic Nicotine Dependence Center in Rochester, Minn. "Studies have found that a standard dose of patch therapy results in a cotinine level-the nicotine metabolite—of only about half what the patient would get through smoking. Heavy smokers in particular need more treatment."

If your patients use a patch, for example, Dr. Hurt recommended asking how many cigarettes they smoke each day to establish the right level of nicotine replacement. He gave these guidelines, which he uses in his practice:

  • Patients who smoke fewer than 10 cigarettes per day need a patch dose of 7 mg to 14 mg per day.
  • Patients who smoke between 10 and 20 cigarettes a day need a dose of 14 mg to 22 mg per day.
  • Patients who smoke between 21 and 40 cigarettes daily need a patch dose of 22 mg to 44 mg daily.
  • Heavy smokers—people who smoke more than 40 cigarettes a day-need at least 44 mg per day from the patch.

Another key to successful smoking cessation strategies is giving patients detailed instructions. "I would not encourage gum usage unless you spend a few minutes explaining how to use it," said Tim McAfee, MD, executive medical director for the Center for Health Promotion at Group Health Cooperative of Puget Sound in Tukwila, Wash. Tell patients not to chew the gum, but rather take a few bites until the gum's distinct taste indicates nicotine is being released. At that point, Dr. McAfee said, patients should hold the gum between their teeth and gum so the nicotine can be absorbed through the oral mucosa.

And if patients are using gum only, give them a schedule that specifies when they should use it. "You need to put them on a regimen," Dr. McAfee said. (Guidelines from the U.S. Public Health Service recommend one piece per hour, up to 24 pieces per day.)

Dual therapies

Another issue to watch out for: cravings. If your patient has tried to quit before—and many have—and couldn't overcome cravings, you should consider using more than one therapy.

"The nicotine patch is the base product, but if the patient experiences breakthrough withdrawal cravings, you might want to pair it with gum, inhaler or nasal spray," said Nancy A. Rigotti, FACP, director of the Tobacco Research and Treatment Center at Massachusetts General Hospital and Harvard Medical School in Boston. This dual therapy will give a steady background nicotine level and allow patients to increase their nicotine intake when they experience cravings.

Dual therapies illustrate one of the great challenges of smoking cessation. While nicotine replacement therapies deliver nicotine in different ways, none are as efficient as smoking.

Cigarettes, after all, pump nicotine into the bloodstream quickly and give smokers easy access to the drug any time they wish. Nicotine enters the bloodstream within five to seven heartbeats after a puff on a cigarette.

With the patch, on the other hand, blood nicotine levels peak within two to four hours and stay constant for 16 or 24 hours, depending on the dosage. Other smoking cessation drugs peak much sooner and don't last as long. Nasal sprays, for example, work within five to 10 minutes, and both the gum and inhaler work within 20 minutes.


Duration is another critical consideration of smoking cessation treatments. Dr. Hurt said that under physician guidance, most patients use the patch for four to eight weeks. (The FDA has approved the patch for a maximum of eight weeks.) Dr. Hurt, however, explained that it is safe to use the patch longer if necessary. Smokers trying to quit on their own tend to use the patch for even less time, making it far less effective. Dr. McAfee from Group Health, for example, said that most people who purchase patches over-the-counter on their own use them an average of one to two weeks.

FDA-approved timeframes for taking the other drugs range from seven to 12 weeks for bupropion and three to six months for nicotine vapor inhalers and nasal sprays.

Contraindications and side effects

In a few circumstances, smoking cessation medications may be contraindicated. Pregnant smokers, for example, should first try to quit without medications.

Dr. Rigotti, however, said that if a pregnant smoker does not succeed in quitting with a behavioral program, it is safer to have her use nicotine replacement drugs than to continue smoking. She noted that many obstetricians prescribe nicotine replacement therapies in this situation.

In addition, the safety of nicotine replacement therapies has not been established in patients who have had myocardial infarction in the past two weeks and in patients with severe or unstable angina. U.S. Public Health Service guidelines say that you can use the products with these patients, but you should prescribe with caution.

The safety of nicotine patches in patients who have stable angina or have had a heart attack more than two weeks ago has been demonstrated in randomized studies. Dr. Rigotti said that physicians should not hesitate to use the patch in these patients.

Remember that nicotine replacement can create problems for some patients. The patch, for example, can cause skin irritation and "insomnia or excessively vivid, disturbing dreams," according to Dr. McAfee, and nasal sprays can also cause nasal irritation. Some patients have also reported difficulty tapering their use of nasal sprays because their mechanism of delivering nicotine to the brain is so similar to cigarettes, he added.

Experts suggest that you talk about nicotine withdrawal symptoms, possible side effects and the appropriate use of drugs before starting treatment to prepare patients and head off some problems. Removing the patch before going to bed, for example, may help prevent disturbing dreams.


If your patient wants to quit smoking and has a history of depression or is currently battling the disease, bupropion may be a good choice because it doubles as an antidepressant.

What if your patient is already taking an antidepressant? Experts say that under certain circumstances, you can give bupropion to patients who are already taking low doses of selective serotonin reuptake inhibitors (SSRI) like fluoxetine or paroxetine. Dr. McAfee said that if you combine the two therapies, however, you should consider having the patient take 150 mg of bupropion once a day. Bupropion studies suggest that long-term cessation rates are equivalent at one year for 150 mg and 300 mg.

Dr. McAfee added that it's probably not a good idea to switch a patient to bupropion from an SSRI solely for the purpose of smoking cessation. "I have done it, but only with patients who were not happy with the SSRI anyway," he said. He added that he would be cautious about making the switch because smoking cessation increases the likelihood of depression relapse. Switching from an anti-depressant that is working well for an individual to an untried one solely to help the patient stop smoking may have unpredictable results.

Bupropion can also be a good choice for patients who don't want to wear a patch. Family physician Gregg Omura, MD, of Grand Junction, Colo., said he regularly favors bupropion over nicotine patch therapy. "I'm not a great advocate of patches," he explained. "I think the psychological addiction of nicotine is greater than the physical aspect."

Bupropion is not recommended for people with histories of seizures, serious head traumas with a loss of consciousness or eating disorders, or for patients taking other medications that lower the seizure threshold. It should be started seven days before a patient's scheduled quit date in order to have adequate levels in the system.

While experts say that bupropion can produce fairly mild side effects like insomnia and dry mouth, the symptoms can be enough to cause some patients to stop therapy. Dr. McAfee said there are two ways to get around this problem. First, you can have the patient take the second dose earlier in the day, at around 5:00 p.m. instead of 8:00 p.m. Second, you can suggest patients take the drug once a day instead of twice a day and cut back to a single, 150-mg dose.

As with other smoking cessation therapies, pairing bupropion with the patch may be a good choice for patients who have unsuccessfully tried to quit many times or smoke heavily.

Patient preferences

Some final tips: In many cases, absent any contraindications, the decision about which drug to use comes down to patient preference, past experience with the products and insurance coverage.

"I try to find out about patients' previous experiences trying to quit," explained Anne M. Joseph, ACP- ASIM Member, assistant professor of medicine at the Minneapolis Veterans Administration Hospital and the University of Minnesota. "The vast majority have made prior attempts, and if they had success with a certain agent, but had a late relapse, then I'll retry them on that agent."

And don't automatically accept at face value patients' statements that previous products didn't work. "You need to delve a little deeper to understand why they think they didn't work," Dr. McAfee said. "The patient might say the therapy didn't work, but what really happened is that he had a relapse after six months."

Finally, while drug therapy will give your patients a critical edge in kicking the habit, studies show that the best way to make sure they quit for good is to provide education and support. Dr. McAfee suggested scheduling check-back visits with physicians or nurses, calling patients to check on their progress, or referring them to smoking-cessation resources in the community. (For more on how to motivate patients to stop smoking, see "How you can convince patients it's time to quit," below.)

Gina Rollins is a freelance writer in Silver Spring, Md.

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP-ASIM.


Second-line therapies for smoking cessation

If your patient can't take any of the first-line smoking cessation drugs, you can choose from two second-line therapies.

Nortriptyline is a tricyclic antidepressant, and clonidine is an antihypertensive agent. While neither drug has FDA approval for tobacco dependence treatment, both have been effective in clinical trials.

"I use nortriptyline, but rarely," said Tim McAfee, MD, executive medical director for the Center for Health Promotion and Tobacco Programs at Group Health of Puget Sound in Tukwila, Wash. "I prescribe it to patients who have a strong history of depression, do not want to use patches and for whom bupropion is strongly contraindicated, such as patients with a seizure disorder or a bupropion allergy."

For clonidine, however, some of the side effects—particularly drowsiness and dizziness—are intolerable for certain patients and keep it from being prescribed more widely, according to Nancy A. Rigotti, FACP, director of the Tobacco Research and Treatment Center at Massachusetts General Hospital in Boston.

Second-line therapies offer one big advantage: cost. At about $1 per day, both nortriptyline and clonidine cost about one-third as much as bupropion, and one-sixth or less what nicotine replacement therapies cost.

This is significant, considering the poor coverage available for nicotine dependence treatment. Fee-for-service Medicare does not pay for smoking cessation medications. HMOs generally do, but coverage among other payers is spotty.


Smoking cessation resources


How to convince patients it's time to quit

By Gina Rollins

Nowhere do the science and art of medicine interact more than when you're working with patients to stop smoking.

The science is well-established. Nicotine is highly addictive and should be treated like a chronic disease. In addition, smoking cessation almost always requires repeated attempts, and even brief counseling from a physician boosts cessation rates.

The art, however, is a little trickier. You want to motivate patients so they actually want to quit, gently nudging them to explore the reasons they smoke and the barriers that keep them from kicking the habit.

While you need to persistently tout the benefits of smoking cessation, you can't nag patients so much that they stop listening. You must instead find the motivation that best fits each patient's individual circumstances—and do it in just a few moments of your already-packed patient visits.

To make this delicate choreography of facts and persuasion easier, experts say, make it a regular part of your office routine. "Smoking cessation should be part of primary care and incorporated into your practice rather than isolated sledgehammer incidents," said Tim McAfee, MD, executive medical director for the Center for Health Promotion at Group Health Cooperative of Puget Sound in Tukwila, Wash. "Even a brief mention is one of the most important things we can do as physicians."

Nancy A. Rigotti, FACP, director of the Tobacco Research and Treatment Center at Massachusetts General Hospital and Harvard Medical School in Boston, said that preparing patients to kick the habit usually requires a long-term effort. "To get patients to the point of quitting, keep bringing it up at every visit in a nonthreatening, nonjudgmental way," she said. "You build empathy by acknowledging their ambivalence about stopping, supporting their autonomy to make a responsible decision, and bolstering their self-confidence to make a change."

To start, she said, consider creating a system in your practice so that you're not working alone to identify which patients smoke. "Even a simple thing like having your medical assistant check and mark smoking status on the chart will remind you to mention it," Dr. Rigotti explained.

The five Rs

Motivational interviewing techniques are emerging as a popular smoking cessation strategy. First used in treating drug addiction, motivational interviewing techniques prompt patients to explore their reasons for smoking and barriers to stopping. The technique can eventually help smokers go from merely thinking about quitting and become determined enough to stop that they actually try to quit.

Guidelines from the U.S. Public Health Service, for example, suggest using the 5 "R"s: relevance, risks, rewards, roadblocks and repetition.

  • Relevance. Ask patients to indicate why quitting is important to them.

  • Risks. Address the specific risks patients face by continuing to smoke. This allows you to introduce other variables that might be significant to them, such as how secondhand smoke affects their families.

    "It's often a very powerful thing to put smoking in the context of other things you're doing with their health and to say, 'If you quit, it will do more than any of these other treatments,' " said Anne Joseph, ACP-ASIM Member, assistant professor of medicine at the Minneapolis Veterans Administration Hospital and the University of Minnesota.

  • Rewards. It's easy to focus on all the negatives associated with smoking, but don't forget to ask patients what they see as rewards to stopping. Patients may look forward to cleaner breath, for example, or saving money they used to spend on cigarettes.

  • Roadblocks. Ask smokers why they continue to smoke. Their answers may provide insight about overcoming the barriers they face as they try to stop smoking.

  • Repetition. Repeat the process until patients are ready to try to kick the habit. Even if your other motivational remarks don't hit home, experts say, sheer repetition will often break through.

    "Patients realize that if doctors keep talking about not smoking, it must be important," said Jasjit S. Ahluwalia, FACP, chair of the department of preventive medicine at the University of Kansas Medical School in Kansas City.

Other resources

Not every patient needs additional support like smoking cessation counseling, but it can often be the key to success. Patients trying to quit for the third or fourth time, those with a history of depression, or individuals who lack significant social or family support often gain the most from counseling.

Prepare a list of resources in your community or a list of places where patients can access such information. Various nonprofit groups like the American Cancer Society, American Lung Association and American Heart Association offer smoking cessation classes, and 28 states now offer telephone hotlines to help people quit. Manufacturers of smoking cessation drugs also offer toll-free hotlines.

Consider stocking up on pamphlets that explain the smoking cessation process. This material will help reinforce your explanation of withdrawal symptoms and the chronic nature of nicotine dependence.

If at all possible, contact patients a few days into their attempts to quit. Experts say that nicotine withdrawal symptoms typically peak at about that time, making patients very vulnerable to picking up a cigarette again.

"Just a phone call from a nurse is shown to be effective," said Dr. Ahluwalia. "It doesn't have to be the doctor."

Finally, after shepherding a patient through a quit attempt, don't be surprised or frustrated if you have to go through the whole process again.

"Remember, quitting smoking is a process that involves unlearning behaviors and breaking a nicotine addiction," Dr. Rigotti advised. "It takes time, so don't be disappointed when patients fail or don't want to try. Keep working with them."

Gina Rollins is a freelance writer in Silver Spring, Md.

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP-ASIM.


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