American movies often glamorize the singular efforts of their heroes or heroines. Early audiences were thrilled to see tall handsome heroes in Westerns face the bad guys alone at high noon on Main Street and bring them to justice. Later audiences cried when strong-willed women overcame outdated standards to achieve personal, social, or economic success. It's no wonder, then, that we often hear people express the belief that overcoming another hardship—beating a tobacco habit—is something to be accomplished alone. Whether this springs from culture or from unfamiliarity with therapeutic options, the truth is that no one need go unarmed or unaccompanied into battle with nicotine addiction.
Physicians, pharmacists, and counselors are professionals who can join smokers in their fight to overcome a tobacco habit. They bring with them nicotine replacement therapies in an array of forms to help tobacco users meet the challenge, whether it is a teenager who needs a therapy that is not evident to peers or an adult who needs the oral stimulation provided by gum or lozenges. They also have drugs that can ameliorate the ups and downs of nicotine withdrawal. Professionals can tailor the therapy to meet the patient's needs.
Patients can choose an individual course. They can choose a pharmacologic aids to help or they can choose nonpharmacologic methods: stopping cold turkey, tapering use, undergoing individual psychological therapy or participating in group therapy, or reading self-help materials and following the advice. Most effective—that is, the method most likely to help a person quit smoking and sustain abstinence— is using a combination of these therapies. Because a combination of a nicotine replacement therapy and an antidepressant is dramatically more effective than a single therapy alone, the government's report on treating tobacco dependence urges that "all patients attempting to quit should be encouraged to use effective pharmacotherapies for cessation except in the presence of special circumstances."
First-line therapies for smoking cessation are (a) nicotine replacement therapy, which is available in many forms (gum, patches, lozenges, nasal spray, and an oral inhaler), and (b) a psychotropic drug (bupropion/Zyban). Nicotine gum first became available about two decades ago, but lozenges only emerged in 2002 (Fig. 1).
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Second-line pharmacologic therapies, which have proven efficacy in helping patients to quit but do not have an FDA indication for smoking cessation and have undesirable side effects compared to first-line agents, include clonidine (Catapres) and nortriptyline (Pamelor;Aventyl), both available by oral administration. Clonidine also comes in a transdermal patch. With these therapies, the estimated odds of quitting relative to placebo range from 1.7 (nicotine patch and gum) to 2.7 (nasal spray) (Fig. 2).
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For patients unable to quit with monotherapy, there is evidence of benefit when agents are used in combination. For example, the use of bupropion with the nicotine patch increased quit rates an estimated 5.2 percentage points, from 30.3% to 35.5% (Fig. 3).
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Pharmacotherapy is thought to be effective because it reduces the effects of physical withdrawal from nicotine, permitting patients to focus on behavioral and psychological aspects of tobacco cessation. Nicotine replacement therapy results in lower levels of nicotine than smoking and does not provide the rapid satisfaction as that of smoking. Here we will examine first-line medications for cessation. Each section concludes with the bottom line—advantages and disadvantages of the recommended therapy. The medications cannot be rank ordered by effectiveness because there is insufficient information to demonstrate superiority of one agent over another. Instead the medications are organized by their non-prescription verses prescription classes. We begin with over the counter therapies (nicotine gum, transdermal nicotine patch, and nicotine lozenge) and conclude with prescription therapies (nicotine nasal spray, nicotine oral inhaler and bupropion).
Nicotine gum, sold without a prescription since 1996, remains a commonly used nicotine-replacement therapy. Nicorette and its generic form offer nicotine in a resin complex with polacrilin in a sugar-free chewing gum base. Like the nicotine lozenges, nicotine gum is available in two formulations (2 mg and 4 mg). It also may be purchased in regular, mint, or orange flavors. Choosing the right dose is based on how many cigarettes the patient smokes per day: if the patient smokes fewer than 25 cigarettes per day, the prescriber should choose the 2-mg form; if the patient smokes 25 or more cigarettes per day, then the 4-mg dose is recommended. The gum appears to be particularly helpful with patients who have weight gain concerns or who report boredom as a trigger for smoking. However, those with dental appliances or dentures sometimes find it is the one nicotine replacement therapy they cannot use because the highly viscous gum can cause havoc with expensive dental work.
Chewing nicotine gum requires careful patient education. Patients should be instructed on when to chew and when not chew the gum. This is because chewing releases the nicotine, and once the tingling sensation of nicotine affects the buccal membranes, the gum should be not be chewed —it should be "parked"—until the tingle fades. Here are the instructions every patient needs to use nicotine gum effectively:
Chew too slowly and the nicotine craving may not be satisfied promptly. Chew too quickly and excessive nicotine may be released, causing lightheadedness, nausea and vomiting, feelings of indigestion, irritation of throat and mouth, and hiccups. It is recommended that patients who want to improve their chances of quitting not use less than nine pieces of gum daily at the initiation of therapy. The effectiveness of nicotine gum may be reduced by acidic beverages such as coffee, juices, wine, or soft drinks. These beverages transiently reduce the salivary pH, resulting in decreased absorption of nicotine across the buccal mucosa. Patients should be advised not to eat or drink for 15 minutes before or while using the nicotine gum.
Despite the importance technique takes on when using nicotine gum, be reassured that it can be mastered and about a fifth of all patients who use it are able to be tobacco free at more than 5 months after quitting. Like other nicotine- replacement therapies, nicotine gum should be tapered off. Some patients like to decrease the time they chew each piece; others like to decrease the number of pieces they chew.
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Discrete and little trouble, the transdermal nicotine patch delivers continuous nicotine directly to the systemic circulation. Plasma nicotine levels obtained with the patch are approximately 50% lower than those achieved with cigarette smoking. Lower levels of nicotine still alleviate the symptoms of withdrawal but are far less likely to lead to dependence when compared to tobacco or other forms of NRT. There are four marketed transdermal nicotine formulations. Three of the products (Nicoderm CQ and two generic formulations) deliver the labeled dose of nicotine continuously over 24 hours. The Nicotrol formulation provides continuous nicotine delivery over 16 hours. This system, which more closely approximates typical smoking patterns, is applied in the morning and removed at bedtime. The dosing schedules for the nicotine patches vary (Table 2).
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Before recommending a specific product and a dosing schedule, it is important to know how many cigarettes the patient smokes per day and if he or she has strong morning cravings for cigarettes. In general, heavy smokers will require higher strength formulations for a longer duration of therapy. Patients with strong morning cravings for cigarettes might have better success with a 24-hour patch. Some patients may need to switch patch strengths during the first two weeks of therapy to determine correct strength. Patients experiencing substantial withdrawal symptoms or cravings should increase to a higher dose. Patients experiencing side effects (e.g., dizziness, perspiration, nausea, vomiting, diarrhea, headache) should consider a lower dose.
Because the patch is applied directly to the skin, dermatologic conditions become a major concern. Choose an area of skin on the torso or the top outside area of the arm that is naturally hairless, and clean and dry. Do not use an area with inflammation, a burn, or any type of irritation. These conditions interfere with nicotine absorption. Patches should be placed on a different area each time, and no area should be reused for at least 1 week. Patients with psoriasis, eczema, atopic dermatitis, or other similar dermatologic conditions are not good candidates for this method of therapy.
To make sure the patch is firmly in place, apply pressure with the palm of the hand for about 10 seconds. Once the patch is adhered cohesively to skin around all edges, it can almost be forgotten until time to change it. Water and perspiration should not compromise the delivery of nicotine, and patients can bathe, swim, shower, and exercise without worry. However, there is one word of warning: patients should wash their hands carefully after applying the patch because nicotine that haphazardly gets in the eyes or nose from the hands can be irritating.
Immediate side effects include mild itching, burning, and tingling. Later, vivid dreams, sleep disturbances, or headache may cause discomfort. Though it is normal for the covered skin to appear red after patch removal, any inflammation that persists for more than 4 days should be reported to a physician and patch therapy at least temporarily discontinued. Half of patients experience local erythema, burning, and/or pruritus, but less than 5% discontinue therapy.
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Called "Commit," this newly approved NRT delivers about 25% more nicotine than an equivalent gum dose and is available in a 2-mg and a 4-mg mint-flavored lozenge.
Unlike other NRT formulations in which the dosage is based on the number of cigarettes smoked per day, the nicotine lozenge is dosed based on the how long the patient can wait until the first cigarette of the day. Patients who smoke their first cigarette of the day within 30 minutes of waking should use the 4-mg strength lozenge. Patients who smoke their first cigarette of the day more than 30 minutes after waking should use the 2-mg strength. It is recommended that during the first six weeks of therapy patients take no more than 20 lozenges per day but no fewer than nine. In general, patients should use one lozenge every one to two hours while awake. Lozenges take about 20–30 minutes to dissolve, but may take longer. By the seventh week, patients should extend the interval between doses to about half the initial dose (1 lozenge every 2–4 hours). After 3 weeks on that schedule, the recommended dosage is cut again to about half (1 lozenge every 4–8 hours).
Difficult for some patients are the restrictions on eating and drinking associated with lozenge use. Proper use of the lozenge requires the patient to refrain from chewing or swallowing it (to prevent excessive release of nicotine) and to occasionally rotate the lozenge to different areas of the mouth while it dissolves (to reduce mouth irritation). Furthermore, patients must not eat or drink for 15 minutes before or while using the lozenge so as not to decrease nicotine absorption across the lining of the mouth. Although the lozenge may satisfy some of the oral cravings patients experience while trying to quit, it will not provide the rapid satisfaction that smoking provides. The lozenge is generally well tolerated with nausea, hiccups, cough, heartburn, headache, flatulence, insomnia reported in less than 5% of patients.
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Rapidly absorbed across the nasal mucosa, nicotine nasal spray delivers 0.5 mg nicotine in each metered 50-µL dose of spray. One dose (1 mg nicotine) includes a metered spray in each nostril. Patients usually start with 1–2 doses per hour, but dosing should not increase beyond 5 doses per hour daily. Patients should use at least 8 doses daily for the first 6-8 weeks of therapy. Gradually tapering the dose over an additional 4–6 weeks should successfully lead to termination of therapy. Patients need about one bottle of spray per week.
Side effects during the first week are similar to those of a typical cold: sneezing, coughing, watery eyes, and a runny nose. Accompanying these is a hot peppery feeling in the back of the throat or the nose. Though these effects of the spray are irritating, with regular use, they should lessen during the first week of therapy. If patients experience persistent irritation, they should contact the prescriber. At this follow-up visit, it is important to make sure that the patient is not using the product more than five times per hour or 40 times per day. Patients with chronic nasal disorders (e.g., rhinitis, polyps, sinusitis) or patients with severe reactive airway disease should not use this form of NRT because of the irritant effects of the spray.
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More than any other nicotine replacement therapy, the nicotine inhaler is most like smoking. Similar, in fact, to a cigarette holder, the nicotine inhaler is held to the mouth like a cigarette, its nicotine vapor is inhaled like cigarette smoke, and then it is removed from the mouth after inhalation, just like a cigarette. But what looks, feels, and may taste like a cigarette, in this case, isn't a cigarette. Available by prescription since 1997, the nicotine inhaler comprises a two-part mouthpiece into which the patient presses and inserts a nicotine cartridge. Pressing causes the cartridge's seal to break and permits the nicotine to escape the cartridge (Figure 4).
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When the patient puts the mouthpiece to the lips and inhales, the nicotine turns to vapor which is absorbed across the oropharyngeal mucosa. Puffing in short breaths (as if smoking a pipe) is the recommended way to use the nicotine inhaler. It is not to be inhaled like a cigarette (deeply into the lungs)
Unlike a cigarette that once lit is smoked or lost, the cartridge maintains its potency for 24 hours, so it does not have to be used all at once. Active inhaling or puffing, however, will deplete one in about 20 minutes. Initially, patients may use between 6 and 16 cartridges per day, as needed. Therapy may extend from 3 to 12 weeks, but an additional 6–12 weeks may be necessary to achieve complete cessation. Mouthpieces, though they require routine cleaning with detergent, are reusable.
First-time users sometimes experience an unpleasant taste, others report a cough, and still others say they have mild irritation in the mouth or throat. These symptoms too have parallels in smoking. Most adapt to these discomforts in a short time. Less common side effects reported include rhinitis, dyspepsia, hiccups, and headache.
During therapy, patients are warned to avoid eating or drinking for 15 minutes before using the inhaler and throughout the time they are inhaling or puffing. Some foods and beverages are thought to affect the therapy's effectiveness, and temperatures below 59ºF may compromise vapor delivery. As with the nicotine gum and lozenge, patients should be advised not to eat or drink for 15 minutes before or while using the nicotine inhaler. It is recommended that patients use the nicotine dose of the inhaler completely and take doses more often during initial therapy to help control tobacco cravings. Continual puffing during the 20 minutes achieves maximal effect. As cravings subside, patients may find that skipping doses is a good method for reducing the dosage.
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Sustained-release bupropion (Zyban) fights nicotine dependence by decreasing the craving for cigarettes and ameliorating the symptoms of nicotine withdrawal by affecting dopamine and norepinephrine levels in the brain. To ensure therapeutic plasma levels of drug when patients quit, the manufacturer recommends patients initiate therapy one to two weeks before their quit date. For the first three days, patients take 150 mg every morning. If the medication is tolerated, patients increase the dosage to 150 mg twice a day for 7 to 12 weeks. Because it increases the risk of seizure, it should be avoided in anyone with a history of seizures or those taking medications that lower the seizure threshold. Physicians are advised that bupropion also is contraindicated for patients with a history of anorexia or bulimia nervosa and should be used with extreme caution in severe liver cirrhosis. Patients undergoing therapy with Wellbutrin, Wellbutrin SR, or monoamine oxidase inhibitors, and those abruptly discontinuing alcohol or sedatives (including benzodiazepines) are not candidates for bupropion therapy. Women who are pregnant should try nondrug treatment first.
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Combining types of nicotine-replacement therapy (e.g., sustained patch therapy combined with therapy in which dose can be titrated (gum, lozenge, inhaler, or nasal spray therapy) is usually reserved for patients for whom monotherapy fails to help them quit. In addition, providers sometimes prescribe second-line agents (clonidine and nortriptyline) for patients unable to use first-line medications.
Overall, medications for tobacco cessation approximately double the long-term quit rates compared to placebo. Little information is available to substantiate the use of one form of pharmacotherapy over another for a given patient. The choice of therapy is therefore largely based on patient preference and tolerability of the available dosage forms. Pharmacotherapy should be combined with behavioral counseling to further increase patients' chances for success. In the next module, we'll look at smoking among special populations. The groups we will examine include pregnant women, parents of infants and young children, and adolescents. We will also explore the role that genetics plays in tobacco use.
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