BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine from cigarettes. This reduces withdrawal symptoms associated with smoking cessation thus helping resist the urge to smoke cigarettes. OBJECTIVES: The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; 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; to determine whether combinations of NRT are more effective than one type alone; and to determine its effectiveness compared to other pharmacotherapies. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register in July 2002. SELECTION CRITERIA: Randomized trials in which NRT was compared to placebo or no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow-up of less than six months. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects, the dose and duration and form of nicotine therapy, the outcome measures, method of randomization, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model (Peto). MAIN RESULTS: We identified 110 trials; 96 with a non NRT control group. The odds ratio for abstinence with NRT compared to control was 1.74 (95% confidence interval 1.64 - 1.86), The odds ratios for the different forms of NRT were 1.66 for gum, 1.74 for patches, 2.27 for nasal spray, 2.08 for inhaled nicotine and 2.08 for nicotine sublingual tablet/lozenge. These odds were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2mg gum (odds ratio 2.67, 95% confidence interval 1.69 - 4.22). There was weak evidence that combinations of forms of NRT are more effective. Higher doses of nicotine patch may produce small increases in quit rates. Only one study directly compared NRT to another pharmacotherapy, in which bupropion was significantly more effective than nicotine patch or placebo. REVIEWER'S CONCLUSIONS: All of the commercially available forms of NRT (nicotine gum, transdermal patch, the nicotine nasal spray, nicotine inhaler and nicotine sublingual tablets/lozenges) are effective as part of a strategy to promote smoking cessation. They increase quit rates approximately 1.5 to 2 fold regardless of setting. The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the smoker. 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.

Nicotine replacement therapy for smoking cessation.

Evidence for benefit from nicotine replacement therapy in hospital patients is inconclusive, although the results of a trial reported in this issue of Thorax give cause for optimism and should stimulate further studies.

Most smokers become nicotine dependent and, when they stop smoking, experience withdrawal symptoms and craving. Nicotine replacement therapy (NRT) reduces these unpleasant symptoms and, theoretically, should decrease the risk of relapse. Smoking cessation is properly defined as validated sustained abstinence from cigarettes and/or other tobacco products for at least 6 months, but preferably for 1 year. This editorial includes evidence only from those studies which have applied such a definition and which have specified their settings and populations.

NRT is available as chewing gum, transdermal patches, sublingual tablets, lozenges, inhalation cartridges and nasal spray. In specialised cessation clinics1–8 and in primary care,9,10 prospective randomised clinical trials have shown that NRT, used as an adjunct to advice and support, results in better cessation rates than does advice and support alone. In the clinics success rates with NRT tend to be higher (11–30%) and more consistent than in primary care, where some studies have found no significant difference from placebo.11–14 One study in primary care showed 8% success with nicotine chewing gum compared with 4% with advice plus leaflet, but there was no placebo controlled arm.15 Two studies of transdermal nicotine in primary care have shown success rates of around 10%, which were superior to those with placebo (around 6%).9,10 The benefit for transdermal nicotine in cessation clinics6–8 and in primary care9,10 is thus clear, whereas nicotine chewing gum,1–5 inhaler,16,17 …

https://thorax.bmj.com/content/thoraxjnl/58/6/464.full.pdf

Nicotine replacement therapy in smoking cessation

Objective To describe weight gain and its variation in smokers who achieve prolonged abstinence for up to 12 months and who quit without treatment or use drugs to assist cessation. Design Meta-analysis. Data sources We searched the Central Register of Controlled Trials (CENTRAL) and trials listed in Cochrane reviews of smoking cessation interventions (nicotine replacement therapy, nicotinic partial agonists, antidepressants, and exercise) for randomised trials of first line treatments (nicotine replacement therapy, bupropion, and varenicline) and exercise that reported weight change. We also searched CENTRAL for trials of interventions for weight gain after cessation. Review methods Trials were included if they recorded weight change from baseline to follow-up in abstinent smokers. We used a random effects inverse variance model to calculate the mean and 95% confidence intervals and the mean of the standard deviation for weight change from baseline to one, two, three, six, and 12 months after quitting. We explored subgroup differences using random effects meta-regression. Results 62 studies were included. In untreated quitters, mean weight gain was 1.12 kg (95% confidence interval 0.76 to 1.47), 2.26 kg (1.98 to 2.54), 2.85 kg (2.42 to 3.28), 4.23 kg (3.69 to 4.77), and 4.67 kg (3.96 to 5.38) at one, two, three, six, and 12 months after quitting, respectively. Using the means and weighted standard deviations, we calculated that at 12 months after cessation, 16%, 37%, 34%, and 13% of untreated quitters lost weight, and gained less than 5 kg, gained 5-10 kg, and gained more than 10 kg, respectively. Estimates of weight gain were similar for people using different pharmacotherapies to support cessation. Estimates were also similar between people especially concerned about weight gain and those not concerned. Conclusion Smoking cessation is associated with a mean increase of 4-5 kg in body weight after 12 months of abstinence, and most weight gain occurs within three months of quitting. Variation in weight change is large, with about 16% of quitters losing weight and 13% gaining more than 10 kg.

https://www.bmj.com/content/bmj/345/bmj.e4439.full.pdf

Weight gain in smokers after quitting cigarettes: meta-analysis

© 2018 The Cochrane Collaboration. Background: Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Objectives: To determine the effectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions. Search methods: We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search is July 2017. Selection criteria: Randomized trials in people motivated to quit which compared NRT to placebo or to no treatment. We excluded trials that did not report cessation rates, and those with follow-up of less than six months, except for those in pregnancy (where less than six months, these were excluded from the main analysis). We recorded adverse events from included and excluded studies that compared NRT with placebo. Studies comparing different types, durations, and doses of NRT, and studies comparing NRT to other pharmacotherapies, are covered in separate reviews. Data collection and analysis: Screening, data extraction and 'Risk of bias' assessment followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. Main results: We identified 136 studies; 133 with 64,640 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The majority of studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. We judged the evidence to be of high quality; we judged most studies to be at high or unclear risk of bias but restricting the analysis to only those studies at low risk of bias did not significantly alter the result. The RR of abstinence for any form of NRT relative to control was 1.55 (95% confidence interval (CI) 1.49 to 1.61). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 56 trials, 22,581 participants) for nicotine gum; 1.64 (95% CI 1.53 to 1.75, 51 trials, 25,754 participants) for nicotine patch; 1.52 (95% CI 1.32 to 1.74, 8 trials, 4439 participants) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials, 976 participants) for nicotine inhalator; and 2.02 (95% CI 1.49 to 2.73, 4 trials, 887 participants) for nicotine nasal spray. The effects were largely independent of the definition of abstinence, the intensity of additional support provided or the setting in which the NRT was offered. A subset of six trials conducted in pregnant women found a statistically significant benefit of NRT on abstinence close to the time of delivery (RR 1.32, 95% CI 1.04 to 1.69; 2129 participants); in the four trials that followed up participants post-partum the result was no longer statistically significant (RR 1.29, 95% CI 0.90 to 1.86; 1675 participants). Adverse events from using NRT were related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. Attempts to quantitatively synthesize the incidence of various adverse effects were hindered by extensive variation in reporting the nature, timing and duration of symptoms. The odds ratio (OR) of chest pains or palpitations for any form of NRT relative to control was 1.88 (95% CI 1.37 to 2.57, 15 included and excluded trials, 11,074 participants). However, chest pains and palpitations were rare in both groups and serious adverse events were extremely rare. Authors' conclusions: There is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. NRT often causes minor irritation of the site through which it is administered, and in rare cases can cause non-ischaemic chest pain and palpitations.

Nicotine replacement therapy versus control for smoking cessation

Background—Stopping smoking is associated with many important improvements in health and quality of life. The use of cessation medications is recommended to increase the likelihood of quitting. However, there is historical and renewed concern that smoking cessation therapies may increase the risk of cardiovascular disease events associated within the quitting period. We aimed to examine whether the 3 licensed smoking cessation therapies—nicotine replacement therapy, bupropion, and varenicline—were associated with an increased risk of cardiovascular disease events using a network meta-analysis. Methods and Results—We searched 10 electronic databases, were in communication with authors of published randomized, clinical trials (RCTs), and accessed internal US Food and Drug Administration reports. We included any RCT of the 3 treatments that reported cardiovascular disease outcomes. Among 63 eligible RCTs involving 21 nicotine replacement therapy RCTs, 28 bupropion RCTs, and 18 varenicline RCTs, we found no i...

Cardiovascular Events Associated With Smoking Cessation Pharmacotherapies A Network Meta-Analysis

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi- squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p<0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates. Eur Respir J 1999; 13: 238-246.

https://erj.ersjournals.com/content/erj/13/2/238.full.pdf

Saracci R

Papers

Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial