Stead LF, Perera R, Bullen C, Mant D, Lancaster T

1 Nicotine replacement therapy for smoking cessation (Review) Stead LF, Perera R, Bullen C, Mant D, Lancaster TThis is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published inThe Cochrane Library2008, Issue 3 replacement therapy for smoking cessation (Review)Copyright 2008 The Cochrane Collaboration. Published by John Wiley & Sons, A B L E O F C O N T E N T S1 HEADER ..1 ABSTRACT ..2 PLAIN LANGUAGE SUMMARY ..2 BACKGROUND ..3 OBJECTIVES ..4 METHODS ..8 RESULTS ..13 DISCUSSION ..16 AUTHORS CONCLUSIONS ..17 ACKNOWLEDGEMENTS ..17 REFERENCES ..35 CHARACTERISTICS OF STUDIES ..113 DATA AND ANALYSES ..Analysis Comparison 1 Any type of NRT versus placebo/ no NRT control, Outcome 1 smoking cessation at 6+months follow up.

2 118 Analysis Comparison 2 Subgroup: Definition of abstinence, Outcome 1 Nicotine gum. smoking cessation ..123 Analysis Comparison 2 Subgroup: Definition of abstinence, Outcome 2 Nicotine patch: smoking cessation ..126 Analysis Comparison 3 Subgroup: Level of behavioural support, Outcome 1 Nicotine gum. smoking cessation ..128 Analysis Comparison 3 Subgroup: Level of behavioural support, Outcome 2 Nicotine patch. smoking Comparison 3 Subgroup: Level of behavioural support, Outcome 3 Long versus short support..133 Analysis Comparison 4 Subgroup: Recruitment /treatment setting, Outcome 1 Nicotine gum. smoking Comparison 4 Subgroup: Recruitment /treatment setting, Outcome 2 Nicotine patch.

3 smoking Comparison 4 Subgroup: Recruitment /treatment setting, Outcome 3 Nicotine Inhaler/inhalator. Smokingcessation..139 Analysis Comparison 4 Subgroup: Recruitment /treatment setting, Outcome 4 Nicotine tablet/lozenge. Smokingcessation..140 Analysis Comparison 4 Subgroup: Recruitment /treatment setting, Outcome 5 Nicotine Intranasal spray. Smokingcessation..141 Analysis Comparison 4 Subgroup: Recruitment /treatment setting, Outcome 6 Combination of NRT. Smokingcessation..142 Analysis Comparison 4 Subgroup: Recruitment /treatment setting, Outcome 7 Choice of NRT. smoking Comparison 5 Nicotine gum: 4mg versus 2mg dose,Outcome 1 smoking cessation ..143 Analysis Comparison 6 Nicotine gum: Fixed versus ad lib dose schedule, Outcome 1 smoking cessation .

4 144 Analysis Comparison 7 Nicotine patch: High versus standard dose patches, Outcome 1 smoking cessation at maximumfollow up..144 Analysis Comparison 8 Nicotine patch: 16hr or 24hr use, subgroups & direct comparison, Outcome 1 SmokingCessation..145 Analysis Comparison 9 Nicotine patch: Duration of therapy, subgroups & direct comparison, Outcome 1 SmokingCessation..148 Analysis Comparison 10 Nicotine patch: Effect of weaning/tapering dose at end of treatment, Outcome 1 SmokingCessation..151 Analysis Comparison 11 Combinations of different types of NRT, Outcome 1 Long-term smoking cessation ..153 Analysis Comparison 12 Purchased NRT without support versus physician support, Outcome 1 smoking cessationusing physician prescribed NRT versus NRT without support (allNRT purchased).

5 154 Analysis Comparison 13 Direct comparisons between NRT types, Outcome 1 smoking cessation ..155 Analysis Comparison 14 Precessation treatment with nicotine patch, Outcome 1 smoking cessation ..156 Analysis Comparison 15 Nicotine patch and bupropion; direct comparisons and combinations, Outcome 1 Smokingcessation at longest follow up..157157 FEEDBACK ..160 WHAT S NEW ..160 HISTORY ..iNicotine replacement therapy for smoking cessation (Review)Copyright 2008 The Cochrane Collaboration. Published by John Wiley & Sons, OF AUTHORS ..161 DECLARATIONS OF INTEREST ..161 SOURCES OF SUPPORT ..161 NOTES ..162 INDEX TERMS ..iiNicotine replacement therapy for smoking cessation (Review)Copyright 2008 The Cochrane Collaboration.

6 Published by John Wiley & Sons, Ltd.[Intervention Review]Nicotine replacement therapy for smoking cessationLindsay F Stead1, Rafael Perera1, Chris Bullen2, David Mant1, Tim Lancaster11 Department of Primary Health Care, University of Oxford, Oxford, Trials Research Unit, University of Auckland,Auckland, New ZealandContact address: Lindsay F Stead , Department of Primary Health Care, University of Oxford, Rosemary Rue Building, Old RoadCampus, Oxford, OX3 7LF, group:Cochrane Tobacco Addiction status and date:Edited (no change to conclusions), published in Issue 3, content assessed as up-to-date:31 October : Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking Databaseof Systematic Reviews2008, Issue 1.

7 Art. No.: CD000146. DOI: 2008 The Cochrane Collaboration. Published by John Wiley & Sons, B S T R A C TBackgroundThe aim of nicotine replacement therapy (NRT) is temporarily toreplace much of the nicotine from cigarettes to reduce motivationto smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete 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 effectfor the different forms of NRT (chewing gum, transdermal patches, nasal spray, inhalers and tablets/lozenges) in achievingabstinencefrom determine whether the effect is influenced by the dosage, form and timing of use of NRT.

8 The intensity of additional advice andsupport offered to the smoker; or the clinical setting in which the smoker is recruited and determine whether combinations of NRT are more likely to lead to successful quitting than one type determine whether NRT is more or less likely to lead to successful quitting compared to other strategyWe searched the Cochrane Tobacco Addiction Group trials registerfor papers with nicotine or NRT in the title, abstract or of most recent search July criteriaRandomized trials in which NRT was compared to placebo or to no treatment, or where different doses of NRT were compared. Weexcluded trials which did not report cessation rates, and thosewith follow up of less than six collection and analysisWe 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 main outcome measure was abstinence from smoking after at least six months of follow up.

9 We used the most rigorous definitionof abstinence for each trial, and biochemically validated ratesif available. We calculated the risk ratio (RR) for each study. Whereappropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect replacement therapy for smoking cessation (Review)Copyright 2008 The Cochrane Collaboration. Published by John Wiley & Sons, resultsWe identified 132 trials; 111 with over 40,000 participants contributed to the primary comparison between any type of NRT andaplacebo or non-NRT control group. The RR of abstinence for any form of NRT relative to control was (95% confidence interval[CI]: to ). The pooled RR for each type were (95% CI: to , 53 trials) for nicotine gum; (95% CI: , 41 trials) for nicotine patch; (95% CI: to , 4 trials) for nicotine inhaler; (95% CI: to , 6 trials)for oral tablets/lozenges; and (95% CI: to , 4 trials) for nicotine nasal spray.

10 The effects were largely independent of theduration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. The effect was similarin a small group of studies that aimed to assess use of NRT obtained without a prescription. In highly dependent smokers there wasa significant benefit of 4 mg gum compared with 2 mg gum, but weakerevidence of a benefit from higher doses of patch. There wasevidence that combining a nicotine patch with a rapid delivery form of NRT was more effective than a single type of NRT. Onlyone study directly compared NRT to another pharmacotherapy. Inthis study quit rates with nicotine patch were lower than with theantidepressant conclusionsAll of the commercially available forms of NRT (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/lozenges) can helppeople who make a quit attempt to increase their chances of successfully stopping smoking .