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Am Fam Physician. 2001;63(11):2245-2248

See editorial on page 2130.

See patient information handout on using nicotine replacement therapy, written by the author of this article.

Clinical Scenario

A 32-year-old woman presents with an upper respiratory infection and is advised to quit smoking. The woman has smoked more than one pack per day for more than 10 years, is in the action stage of change (wanting to quit now) and has a Fagerstrom score of 7 (severe dependence).

The Fagerstrom Tolerance Questionnaire (FTQ) is the most widely used tool for assessing severity of nicotine tolerance and dependence.2 It is a seven-item scale with scores ranging from zero to 11 points. The mean score is usually five to seven points with a standard deviation of about two. FTQ scores of seven or above are considered to reflect a high level of dependence.3

Clinical Question

Should you recommend nicotine replacement therapy (NRT) to this patient?

Evidence-Based Answer

Yes. The patient is highly nicotine-dependent, and for smokers with moderate to severe nicotine dependence, nicotine replacement therapy with or without bupropion should be offered as part of an intensive program of physician advice, counseling and follow-up. This answer is based on an evaluation of the Cochrane review summarized below.

Cochrane Abstract

Nicotine Replacement Therapy for Smoking Cessation

Background. The objective of nicotine replacement therapy (NRT) is to replace nicotine from cigarettes. This therapy reduces withdrawal symptoms associated with smoking cessation and helps patients resist the urge to smoke cigarettes.1

Objectives. The goals of this review were to determine the effectiveness of the different forms of NRT (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarette smoking; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used or the intensity of additional advice and support offered to the smoker; and to determine whether combinations of NRT are more effective than monotherapy.

Search Strategy. The author searched the Cochrane Tobacco Addiction Group Trials Register, which includes a number of published articles and abstracts from several scientific disciplines.

Selection Criteria. Randomized trials in which NRT was compared with placebo or no treatment, or where different doses of NRT were compared, were applied. Trials that did not report smoking cessation rates and those with follow-up of less than six months were excluded from the analysis.

Data Collection and Analysis. Two persons independently extracted data on the type of patients, the dose, duration and form of nicotine therapy, the outcome measures, the method of randomization and the completeness of follow-up.

The principal outcome measure was abstinence from smoking after at least six months of follow-up. The authors applied the most rigorous definition of abstinence for each trial and biochemically validated rates, if available. Biochemical validation uses either carbon monoxide breath testing, or urine or serum cotinine levels. When sufficient numbers of patients from similarly designed trials were available, the authors performed meta-analysis using standard statistical methods (fixed effects model).

Primary Results. A total of 94 trials met inclusion criteria: 49 of nicotine chewing gum, 32 of the transdermal nicotine patch, four of intranasal nicotine spray, four of inhaled nicotine and two of the nicotine sublingual tablet. Three trials compared combinations of two forms of nicotine therapy with one form alone.

The odds ratio for smoking abstinence with NRT compared with control was 1.72 (95 percent confidence interval [CI], 1.60 to 1.84). In other words, subjects who used any form of nicotine therapy were 1.72 times more likely than subjects who used placebo or control subjects to be abstinent at six months or more. The odds ratios for the different forms of NRT were 1.63 for gum, 1.77 for transdermal patches, 2.27 for intranasal nicotine spray, 2.08 for inhaled nicotine and 1.73 for nicotine sublingual tablet. These odds were largely independent of the intensity of additional support provided or the setting in which the NRT was offered. Eight weeks of patch therapy were as effective as longer courses of therapy, and there was no evidence that tapered therapy was better than abrupt withdrawal of NRT. Wearing the patch only during waking hours (16 hours per day) was as effective as wearing it 24 hours per day. The odds ratio for abstinence in the trials that directly compared 4-mg gum with 2-mg gum in highly dependent smokers found a significant benefit in favor of 4-mg gum (odds ratio, 2.67; 95 percent CI, 1.69 to 4.22). There was no strong evidence that combinations of forms of NRT were more effective. Only one study directly compared NRT with another pharmacotherapy (bupropion), and it found that the latter was significantly more effective alone or in combination with the transdermal nicotine patch than the nicotine patch used alone.

Reviewer's Conclusions. All of the commercially available forms of NRT (nicotine gum, transdermal patch and, in some countries, the nicotine nasal spray, nicotine inhaler and nicotine sublingual tablets) are effective as part of a strategy to promote smoking cessation. They increase quit rates by approximately one and one-half to twofold, regardless of setting.

The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the smoker. Because reported trials of NRT have included advice to the smoker about its benefits, advice is the minimum that should be offered to patients to help advance its effectiveness. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT.

There is promising evidence that bupropion may be more effective than NRT (either alone or in combination). However, its most appropriate place in the therapeutic armamentarium requires further study and consideration.

These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (

Cochrane Critique

The authors of the Cochrane review on nicotine replacement therapy addressed a focused and clinically important question. The inclusion criteria were appropriate. This review excluded studies with shorter follow-up because lumping results from shorter follow-up periods (i.e., three months) with longer follow-up periods (i.e., six months) would not be valid. Six-month quit rates for a given population are generally lower than three-month quit rates for that same population, and long-term quit rates are fairly stable after six months. To add short-term quit rates may cause overestimation of long-term abstinence.

It is likely that a small number of unpublished articles may have been missed (publication bias)4,5; however, the authors took extra steps, with limited success, to acquire unpublished studies. The validity of the articles was adequately appraised, and the assessments of the studies are reproducible. Results of the studies were similar. Of the 94 trials reviewed, 87 trials found a beneficial effect of NRT. However, 51 of these trials had odds ratios including unity, meaning they did not reach statistical significance.

When meta-analyses were performed, statistically significant benefits of NRT in any form were found, compared with control or placebo. No benefit was seen for one form of NRT over another; 4 mg of nicotine gum was significantly more efficacious than 2 mg. Bupropion, used alone or in combination with NRT, was more efficacious than NRT. No significant benefits were seen in low-dependency smokers. The results were precise, using pooled odds ratios for six- to 12-month abstinence, but precision may have been limited by assuming that all dropout patients resumed smoking. These results have important implications for the health care of smokers. Conclusions make biological and clinical sense, and the benefits of NRT seem to outweigh the harms.

Practice Pointers

This comprehensive review of 94 randomized control trials of NRT offers compelling evidence for the efficacy of NRT in the treatment of smokers with moderate to severe nicotine dependence. Even in patients with established coronary disease, there is no evidence of negative health consequences resulting from use of the transdermal nicotine patch. Patients should be asked at every visit if they smoke and advised each time to quit. Patients in the preparation stage (wishing to quit in the next 30 days) or action stage (wishing to quit now) with moderate to severe dependence should be offered NRT, bupropion or the combination, unless contraindicated. Physicians should consider the individual barriers to the success of each smoker when choosing the form of NRT, as well as the side effects of each form. For example, physicians may not wish to use a nasal spray in patients with allergic rhinitis.

NRT should be continued for at least eight weeks. Expense is a barrier to implementation of NRT because most insurance companies do not cover the cost. Physicians might consider approaching manufacturers of NRT for samples or entry into clinical trials to cover this expense. Physicians can also inform patients that the monthly cost of cigarettes is about the same or less than the monthly cost of NRT.

Other studies have shown that physician advice, followup, self-help materials, system-wide approaches, nurse advice, and individual and group counseling are effective and can be synergistic with NRT.6 At a minimum, physicians should counsel all smoking patients to quit, provide self-help materials and arrange for follow-up.

Odds ratio
A differentiation of the terms “risk” and “odds” is important in understanding the odds ratio. “Odds” denotes the number of persons with a characteristic (e.g., exposure or disease) expressed relative to the number without the characteristic. Therefore, if two of 10 people are exposed to something (e.g., nicotine replacement therapy [NRT]), the exposure odds are 2:8, whereas the exposure risk is 2/10. The odds ratio is the exposure odds among cases (i.e., quitters) divided by the exposure odds among controls (nonquitters).1 For example, if two of 10 quitters used NRT (odds: 2:8) and one of 10 who did not quit used NRT (odds: 1:9), the odds ratio would be 2:8 divided by 1:9, or 2.27. In other words, smokers who used NRT were 2.27 times as likely to quit smoking as smokers who did not use NRT.
In actual studies, sample sizes are generally much larger, definitions of smokers and quitting are defined more precisely, and more complex statistical methods (i.e., logistic regression) are often used.7

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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