title: Nicotine replacement therapy for smoking cessation.
abstract: BACKGROUND
  The aim of nicotine replacement therapy (NRT) is 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.
  
  
  OBJECTIVE
  The aims of this review were: To determine the effect of NRT compared to placebo in aiding smoking cessation, and to consider whether there is a difference in effect for the different forms of NRT (chewing gum, transdermal patches, oral and nasal sprays, inhalers and tablets/lozenges) in achieving abstinence from cigarettes. To determine whether the effect is influenced by the dosage, form and timing of use of NRT; the intensity of additional advice and support offered to the smoker; or the clinical setting in which the smoker is recruited and treated. To determine whether combinations of NRT are more likely to lead to successful quitting than one type alone. To determine whether NRT is more or less likely to lead to successful quitting compared to other pharmacotherapies.
  
  
  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 July 2012.
  
  
  METHODS
  Randomized trials in which NRT was compared to placebo or to 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.
  
  
  METHODS
  We extracted data in duplicate on the type of participants, the dose, 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. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model.
  
  
  RESULTS
  We identified 150 trials; 117 with over 50,000 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The risk ratio (RR) of abstinence for any form of NRT relative to control was 1.60 (95% confidence interval [CI] 1.53 to 1.68). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 55 trials) for nicotine gum; 1.64 (95% CI 1.52 to 1.78, 43 trials) for nicotine patch; 1.95 (95% CI 1.61 to 2.36, 6 trials) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials) for nicotine inhaler; and 2.02 (95% CI 1.49 to 2.73, 4 trials) for nicotine nasal spray. One trial of oral spray had an RR of 2.48 (95% CI 1.24 to 4.94). The effects were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. The effect was similar in a small group of studies that aimed to assess use of NRT obtained without a prescription. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2 mg gum, but weaker evidence of a benefit from higher doses of patch. There was evidence that combining a nicotine patch with a rapid delivery form of NRT was more effective than a single type of NRT (RR 1.34, 95% CI 1.18 to 1.51, 9 trials). The RR for NRT used for a short period prior to the quit date was 1.18 (95% CI 0.98 to 1.40, 8 trials), just missing statistical significance, though the efficacy increased when we pooled only patch trials and when we removed one trial in which confounding was likely. Five studies directly compared NRT to a non-nicotine pharmacotherapy, bupropion; there was no evidence of a difference in efficacy (RR 1.01; 95% CI 0.87 to 1.18). A combination of NRT and bupropion was more effective than bupropion alone (RR 1.24; 95% CI 1.06 to 1.45, 4 trials). Adverse effects from using NRT are related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. There is no evidence that NRT increases the risk of heart attacks.
  
  
  CONCLUSIONS
  All of the commercially available forms of NRT (gum, transdermal patch, nasal spray, inhaler 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 70%, regardless of setting. The 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.
authors.affiliation: Department of Primary Care Health Sciences, University of Oxford,Oxford,UK. lindsay.stead@phc.ox.ac.uk.
authors.forename: Lindsay F
authors.initials: LF
authors.lastname: Stead
authors.forename: Rafael
authors.initials: R
authors.lastname: Perera
authors.forename: Chris
authors.initials: C
authors.lastname: Bullen
authors.forename: David
authors.initials: D
authors.lastname: Mant
authors.forename: Jamie
authors.initials: J
authors.lastname: Hartmann-Boyce
authors.forename: Kate
authors.initials: K
authors.lastname: Cahill
authors.forename: Tim
authors.initials: T
authors.lastname: Lancaster
mesh_terms: D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D002638:Chewing Gum; D006801:Humans; D009538:Nicotine / Q000008:administration & dosage; D018722:Nicotinic Agonists / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D013607:Tablets; D061485:Tobacco Use Cessation Devices
chemical_list: D002638:Chewing Gum; D018722:Nicotinic Agonists; D013607:Tablets; D009538:Nicotine