A Review of Smoking Cessation Interventions

Ashish Maseeh, MD, and Gagandeep Kwatra, MD

In This Article


Despite considerable evidence supporting the efficacy of different interventions for smoking cessation,[19,20] barely 20% of smokers who try to quit seek professional assistance.[6,21] Both pharmacotherapy and behavioral therapy are effective, but a judicious combination of the 2 has been reported to afford superior results.[22,23,24,25]

Of all pharmacologic agents that have been purported to be effective in smoking cessation, only 2 drugs, namely nicotine and bupropion, are currently approved for this purpose. A vaccine against nicotine is also undergoing clinical trials, and initial results are encouraging.

Attenuating the symptoms of abstinence and satisfying craving by substituting the nicotine of the cigarettes through safer means forms the rationale of nicotine replacement therapy.[12,26] Nicotine replacement therapy has been reported to approximately double the cessation rates compared with placebo[27,28,29] regardless of the extent and intensity of reinforcement with support and encouragement.[2,12] Despite the considerable differences in compliance,[30] kinetics,[28] duration of action, routes of administration, and adverse effects among the various nicotine preparations, the overall efficacy is approximately the same.[30]

Nicotine Gum. Available since 1984,[20] the gum contains either 2 mg or 4 mg of nicotine in an ion resin base "polacrilex" that is buffered in an alkaline pH to optimize buccal absorption.[31]

It requires a special chewing technique to derive optimal therapeutic effect. The gum should be chewed slowly until a pungent "peppery" taste is liberated due to the release of nicotine. It should then be left between the gum and the cheek ("parked") until the taste fades and the process repeated intermittently over 20-30 minutes[4] to release 90% of the available nicotine.[31] Roughly 25% of the released nicotine is swallowed and then metabolized. The bioavailability of nicotine is approximately 53% to 72%, subject to substantial individual variation.[32] Thus, the systemic dose of nicotine using even the 4-mg gum is much inferior to that obtained from smoking.[18,33] A 2-mg gum used regularly throughout the day provides one to two thirds the level of nicotine obtained from smoking[18]

Efficacy: The use of nicotine gum increases cessation rates by 50% to 70%.[19] A meta-analysis of randomized controlled trials found success rates for nicotine gum vs placebo to be 27% vs 18% at 6 months and 23% vs 13% at 1 year, respectively.[32] Higher abstinence rates are achieved when a patch is combined with a 2-mg gum.[34,35] The 4-mg gum has been shown to be much more effective when treating heavily dependent smokers (≥25 cigarettes per day).[20,22]

Dosage: Nicotine gums should be consumed at the rate of 1 per hour up to a maximum of 24 pieces a day to preclude subtherapeutic plasma levels and underdosing that may result in failure of therapy or relapse.[20]

Advantages: The sensory stimulation provided by the gum, in addition to faster onset and shorter duration of action compared with patches,[22] makes it well suited for relief of acute craving.[36] Recently, a gum has been developed that permits even faster release compared with the polacrilex gum, for better nicotine-craving relief.[37]

Unlike with the patch, smokers can control the dose and, thus, can personalize dosage to best suit their needs. The process of using gum constitutes a ritual, in some ways analogous to smoking, which may render a distinct advantage.[7,38] Its availability over the counter makes it accessible to a wider cross-section of smokers even if they do not approach a physician for assistance.[4]

Adverse Effects & Disadvantages: The overall tolerability of the gum is fairly high, with adverse effects usually related to the amount and strength of gum used and improper chewing technique.[38] Commonly encountered adverse effects include jaw fatigue and soreness and gastrointestinal symptoms such as gaseous distension, hiccups, and nausea.[39] An isolated case of breathing difficulties in an asthmatic person has been reported.[20] Approximately 5% to 20% of smokers can become addicted to nicotine gum,[40,41] and acute nicotine withdrawal may occur on abrupt discontinuation.[4] It is contraindicated in patients with gastric ulcers and is unsuitable for denture users.[42]

While improper chewing technique may contribute to inadequate dosage despite compliance, being aware of the per-piece cost, the smoker may restrict his consumption (having too few pieces or discontinuing therapy early[30]) resulting in underdosing and, consequently, therapeutic failure or relapse.[18]

Nicotine Patch. Available since 1991, transdermal patches are designed to release nicotine slowly and steadily when applied to a dry and relatively hairless area of the skin.[43] Plasma levels peak 2-4 hours after application[22] and release occurs over 16 or 24 hours.[20] Immediately after application, there is rapid transfer of nicotine from the patch until steady state is attained. At this point, nicotine exists in the patch, a skin "reservoir," and in the circulation. The reservoir ensures that the plasma levels of nicotine do not decay too rapidly upon sudden discontinuation of patch usage.[7] The patch should not be put in the same place again for at least 1 week and should be removed during strenuous exercise to prevent excessive absorption.[44]

Efficacy: Patches have been shown to increase cessation rates by approximately 1.5 to 2 times compared with placebo[15,45,46,47,48] when used alone. Even better results are achieved when they are used in combination[19,49,50] with other products especially, bupropion.[51,52] Although the short-term efficacy of patches in effecting smoking cessation is good, tolerance may develop over time and the smoker may eventually relapse to smoking.[47] While the high-dose patch is more effective especially while treating highly dependent smokers,[2,53] no difference in efficacy has been demonstrated between the 16- or 24-hour usage patches.[2]

Dosage: Patches are available in different dosage strengths ( Table ) and intended for delivery over 16 hours (15 mg) or 24 hours (7, 14, and 21 mg). Depending upon the degree of dependence[2,53] and body size, treatment should start with the maximum (15 or 21 mg) patches,[39] administered for 8 weeks with tapering doses for the 24-hour patches. In case of adverse effects, such as insomnia, the smoker may switch to the 16-hour patch or a lower dose patch. Because it produces a constant serum concentration of nicotine much less than that with cigarettes,[45] current wisdom advocates reinforcement of the patch with faster and shorter acting products that may help tide over acute craving.[2]

Advantages: The patch is relatively safe and mostly free from serious side effects. It can be worn discreetly, does not require any complex instructions or manipulations, ensures reliable nicotine levels from the first day of use,[45] and carries a low risk of habituation. It can be used by denture users and is safe in patients of gastric ulcer. Simple and once-a-day usage along with easy access may result in a better compliance and outcome[30] compared with other nicotine products.

Adverse Effects & Disadvantages: Adverse effects commonly encountered include local skin irritation, muscle aches or stiffness, sleep disturbances, altered dream patterns, tachycardia, nausea or vomiting, and dizziness[43,44] The dose of nicotine, individual skin characteristics, and the duration of application[43] may influence the incidence and nature of side effects. The user cannot control the dose, and the rate of rise as well as the total plasma levels is far less than that obtained with smoking.[45] Consequently, patches suppress acute nicotine cravings unsatisfactorily, resulting in high long-term relapse rates.

Nasal Sprays. Nasal sprays provide the fastest delivery and the highest nicotine levels[54] among all the nicotine replacement products, although not as much as with cigarettes.[55]

Efficacy: The use of sprays roughly doubles the long-term cessation rates compared with placebo. A randomized double-blind study demonstrated almost 3 times better 6-month efficacy compared with placebo (32% and 12% abstinent patients in treatment and placebo groups, respectively).[55] A recent study[46] reported a better efficacy for patch (21.1%) than for the spray (13.6%), although the combination of the 2 produced the best result (27.1%).

Dosage: Each spray delivers 0.5 mg of nicotine, and a single dose (1 mg) consists of a spray in each nostril. Absorption occurs through the nasal mucosa, and peak plasma nicotine concentrations are reached within 10-15 minutes. The smoker should begin with 1-2 doses per hour and then titrate the dose per his individual requirement up to a maximum of 40 mg per day. This dose should be continued for 6-8 weeks followed by a gradual tapering off (usually by halving the doses, missing a dose, or by reducing the frequency) over 3-6 months[4]

Advantages: The fastest and highest delivery of nicotine among all NRT products, and an ability to emulate the nearly instantaneous rewarding effects of cigarette smoke, makes the sprays, ideally suited to control urgent crises faced by an abstaining smoker. Unlike with patches, the user can control the dose using the spray to best cater to their nicotine needs. The alternative sensory stimulus to substitute the ritual of smoking offers a clear advantage.[36]

Adverse Effects & Disadvantages: There is a high incidence of nasal and airway adverse effects associated with the use of sprays that is directly related to the amount of product used.[20] The common adverse effects are irritation of the nose and throat, sneezing, coughing, and watery eyes. Palpitations, nausea, headache, dizziness, and sweating can occur infrequently.[4]

Abrupt discontinuation may precipitate acute withdrawal in some individuals. Sprays appear to have a higher potential for long-term use (beyond the therapeutically recommended period) as opposed to other nicotine replacement products.[54] Its use can be embarrassing, and it also has addictive potential.[43] They may be unsuitable for use in patients with asthma, allergies, nasal polyps, sinus problems, rhinitis, or recurrent epistaxis.[56]

Nicotine Inhaler. Released in 1998, it is more of a "puffer" than an inhaler, composed of a plastic tube that contains a nicotine cartridge. As the patient puffs on the inhaler, the cartridge provides a 4 mg of nicotine vapor from a porous plug (containing 10 mg of nicotine and 1 mg of menthol) that is then absorbed from the mouth.[57] The menthol is an inactive ingredient included to reduce the irritation due to nicotine. Each inhaler can produce approximately 300 puffs, and the same cartridge can be used up to 5 times before replacing with a new one.[58]

Efficacy: Double-blind, placebo-controlled trials have demonstrated individuals to have twice the continuous abstinence rates with nicotine inhalers compared with placebo.[59] As with other NRT products, the efficacy can be enhanced by combining with nicotine patches. Compliance has been reported to be the lowest for the inhaler and nasal spray among all products.[30]

Dosage: Patients should be encouraged to use at least 6 cartridges per day for the first 3-6 weeks of therapy, although, up to 12-16 cartridges can be used.[29] Treatment should continue at the selected dose for a minimum of 1.5 to 3 months followed by a gradual tapering off over 3 months by reducing usage by 25% per month.[60]

Advantages: By mimicking the hand-to-mouth routine of smoking, inhalers can attenuate some of the behavioral difficulties associated with smoking cessation.[4,61] There is less local irritation with the inhaler compared with the nasal spray.[20] The control over the dose that a user has allows better matching with individual needs. The probability of long-term use is markedly less than that with nicotine gum and spray but more than the patch.[4]

Adverse Effects & Disadvantages: Its use is perceived as the most embarrassing among all the NRT products.[30] Because absorption occurs primarily through the mouth, the onset of action of nicotine takes approximately 20 minutes.[62] There is a relative underuse as well as lower compliance for both inhaler and nasal spray, presumably due to their side effects. Adverse effects depend on the amount of use and are primarily limited to the respiratory passage.[20] Abrupt discontinuation can precipitate withdrawal symptoms.

Nicotine Sublingual Tablets and Lozenges. Newer oral forms of nicotine therapy include a microtablet that releases nicotine sublingually and sugar-free nicotine lozenges. Whereas the microtab provides less nicotine than the nicotine gum, the lozenges deliver 25% and 27% more nicotine than corresponding doses of the gum.[63] The mint-flavored lozenge should be sucked slowly until the taste become strong. It should then be kept between the gum and the cheek and slowly sucked again after the taste has faded. Neither should it be bitten into or chewed like a hard candy, nor should it be swallowed. It is not recommended for use along with other nicotine product (gum or patch), and the patient also should not take the lozenge if he continues to smoke or chew tobacco.[43]

Efficacy: A placebo-controlled trial found the odds for abstinence at 6 weeks using 2-mg and 4-mg lozenges to be 2.1 and 3.69 times greater than placebo. The continuous abstinence rates remained greater than placebo even at 1 year. Both 2-mg and 4-mg lozenges reduced craving significantly and greater lozenge use was significantly associated with abstinence at 6 weeks. The success rates achieved with this study approximate the upper range of results reported with other forms of replacement therapy, suggesting that this treatment may be more effective.[63]

Dosage: The sublingual microtabs need to be taken more frequently as they deliver less nicotine and up to 80 mg can be taken per day. Smokers should be encouraged to use at least 7-8 lozenges per day with a maximum of 25 lozenges per day.[29] The recommended dose for the 12-week program is 1 lozenge every 1-2 hours for 6 weeks, followed by 1 lozenge every 2-4 hours for 3 weeks, and finally 1 lozenge every 4-8 hours for another 3 weeks.[43]

Advantages: Both products are easy to use and, unlike the nicotine gum, require no complex instruction or technique for use. The user controls the dose, and higher doses are not associated with any change in the character or pattern of adverse effects. The higher nicotine delivery with lozenges, compared with nicotine gum, may result in higher efficacy. Smoking cessation-related weight gain is significantly reduced with 4-mg lozenges as opposed to placebo. It can be used by denture users, is discreet, and acts fast enough to produce prompt and significant relief from craving.[63]

Adverse Effects & Disadvantages: Both these products share many of the adverse effects associated with nicotine gums, eg, hiccups, irritation in the mouth and throat, belching, dizziness, nausea, and vomiting. Other adverse effects that may occur with lozenges include headache, dizziness, diarrhea, anorexia, dysmenorrhea, and sweating.[44] There exists a possibility of overdose, especially if the individual continues to take some other form of nicotine or if children accidentally consume them.[43] Abrupt discontinuation of the lozenges may precipitate withdrawal symptoms.

Cudgels have been drawn over the safety of replacement therapy in pregnant or lactating women,[20] as well in patients with cardiovascular diseases. While evidence of adverse sequelae of NRT in these groups is as yet wanting, avoidance as far as possible or, cautious use is advised.[53] NRT is safe in patients with stable cardiovascular disease, such as angina pectoris,[64,65,66] but evidence is lacking in acutely unstable patients.[7] Quitting smoking early in pregnancy reduces the risk of low birth weight[6] but pregnant women often find it difficult to quit smoking on their own.[67] All NRT products are pregnancy Category D drugs, except the gum, which is Category C.[4] Despite the risks involved with nicotine administration in pregnancy, it is doubtlessly a preferable alternative to smoking.[68] The risk-benefit ratio appears favorable if efforts to quit without medication have failed[69] and if NRT does, eventually, result in the mother quitting smoking.[53]

Other medical conditions where caution should be exercised are pheochromocytoma (nicotine activates the sympathetic nervous system), recent stroke, inflammation of the mouth or throat, and disorders of the temporomandibular joint (gum may aggravate it).[44] The safety of newer preparations such as lozenges, sublingual tablets, and inhalers in geriatric patients needs further evaluation, and cautious use is advocated. On the whole, however, nicotine replacement therapy has generally been seen to be safe for the vast majority of smokers.[70]

There is negligible direct evidence of the superiority of one form of NRT over another, consequently individual preferences should be accommodated.[2] Replacement therapy with nicotine rarely leads to dependence and, when it does, is less harmful and easier to break than smoking.[29] No doubt NRT should be promoted, but for it to genuinely rival cigarettes, it needs to be made more effective and faster methods of delivery developed. All products produce trough plasma nicotine levels less than half of what a moderately heavy smoker is accustomed to.[45] These factors in addition to the immediately evident adverse effects of replacement therapy (as opposed to the distant prospect of injury to health by smoking) and the prohibitive cost of NRT in many countries, may all contribute in varying degrees to the failures and relapses associated with this therapy.


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