CoChat
Sign Up
Cited by 711Smoking Behavior and CessationSubstance Abuse Treatment and OutcomesPrenatal Substance Exposure Effects

The DOI matches its Crossref record; 426 of the 426 references it cites were found in a registry or an index.

Nicotine replacement therapy versus control for smoking cessation

Open access
Hartmann-Boyce, Jamie, Chepkin, Samantha C, Ye, Weiyu, Bullen, Chris, Lancaster, Tim·2018·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd000146.pub5PMC PMC6353172
Open this paper in CoChat — free accountOpen PDF

Abstract

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1002/14651858.cd000146.pub5

Cites

426 of 426 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 74

  1. Blondal, 1993, Controlled trial of nicotine nasal spray as an aid to stopping smoking [abstract], European Respiratory Journal, 6, 631S
  2. Burton S Campbell IA Prescott RJ Nicotine patches versus placebo in 235 hospital patients [abstract 191] 8th World Conference on Tobacco or Health; 1992 Mar 30-Apr 03; Buenos Aires, Argentina 1992
  3. Grainge, 2011, Double-blind, placebo-controlled, randomised trial of nicotine replacement therapy patches in pregnancy, Journal of Perinatal Medicine, 39, Suppl:172
  4. Dautzenberg B Peiffer G Toulouse F Yvinec MJ Jacob N Kienzler JL Randomized trial assessment of nicotinell lozenge 1mg, a new oral nicotine replacement therapy Society for Research on Nicotine and Tobacco 3rd European Conference; 2001; Paris, France 2001 55
  5. Dautzenberg, 2001, First demonstration of the good efficacy/safety ratio of Nicotinell® 1mg Lozenge (NL 1mg), a new form of nicotine substitution, by randomised clinical trial, European Respiratory Journal, 18 Suppl 33, 12s
  6. Abelin, 1989, Effectiveness of a transdermal nicotine system in smoking cessation studies, Methods and Findings in Experimental and Clinical Pharmacology, 11, 205
  7. Abelin, 1991, Clinical experience with a transdermal nicotine system in healthy nicotine-dependent smokers, 35
  8. Muller, 1990, The use of transdermal nicotine in smoking cessation, Lung, 168, 445, 10.1007/BF02718163 · DOI
  9. Fiore, 1994, Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments, Chest, 105, 524, 10.1378/chest.105.2.524 · DOI
  10. Quílez García, 1993, Treatment for smoking with nicotine gum in primary care. A double blind trial, Revista Clinica Espanola, 192, 157
  11. Glover E Glover P Franzon M Sullivan R Cerullo C Safety and efficacy of a nicotine sublingual tablet for smoking cessation [abstract] Smoke Free 21st Century: 2nd European Conference on Tobacco or Health; 1999; Las Palmas de Gran Canaria 1999
  12. Glover ED Franzon M Sullivan CR Cerullo CL A nicotine sublingual tablet for treating tobacco dependence [Abstract] Society for Research on Nicotine and Tobacco 3rd Europe Conference; 2001 September; Paris, France 2001 48
  13. Glover ED Glover PN Franzon M Sullivan R Sullivan P Howell R A nicotine sublingual tablet for smoking cessation: 6-month data [Abstract] 10th World Conference on Tobacco or Health; 1997 August 24-28; Beijing, China 1997
  14. Hays, 1997, Over-the-Counter (OTC) transdermal nicotine patch therapy [abstract], Journal of Addictive Diseases, 16, 136
  15. Johns D Randomised controlled trial comparing nicotine replacement therapy (nrt) and counselling on smoking cessation in patients prone to lung cancer using bed font micro-smokerlyzer International MASCC/ISOO Symposium: Supportive Care in Cancer; 2017; USA 2017 S102
  16. Kornitzer, 1993, Efficiency and safety of combined use of nicotine patches and nicotine gum in smoking cessation: a placebo controlled double-blind trial [abstract], European Respiratory Journal, 6, 630S
  17. Kralikova, 2002, The clinical benefits of NRT-supported smoking reduction, Nicotine & Tobacco Research, 4, 243
  18. Leischow, 1996, Efficacy of the nicotine inhaler as an adjunct to smoking cessation, American Journal of Health Behavior, 20, 364
  19. Mori T Shimao T Yulchiro G Namiki M Hyachi T A clinical trial of nicotine chewing gum for smoking cessation [abstract 428] 8th World Conference on Tobacco or Health; 1992; Buenos Aires, Argentina 1992
  20. Nakamura M Saito J Oshima A Miyamoto M Matushita A Endo S Effect of nicotine chewing gun in smoking cessation classes The Global War. Proceedings of the 7th World Conference on Tobacco and Health; 1990; Perth, Western Australia Perth Health Department of Western Australia 1990 665 7
  21. Valencia, 2011, Effectiveness of a cognitive orientation program with and without nicotine replacement therapy in stopping smoking in hospitalised patients [Abstract], European Respiratory Journal, 38, 775s [P4224]
  22. Perng, 1999, Randomized, double-blind, placebo-controlled study of transdermal nicotine patch for smoking cessation, American Journal of Respiratory and Critical Care Medicine, 159, A735
  23. Richmond RL Makinson RJ Giugni AA Webster IW General Practitioner smoking interventions in Australia: results of studies over the past ten years The Global War: Proceedings of the 7th World Conference on Tobacco and Health; 1990; Perth, Western Australia Perth Health Department of Western Australia 1990 657 60
  24. Roto, 1987, Nicotine gum and withdrawal from smoking, Suomen Laakarllehtl, 36, 3445
  25. Schneider, 1985, Nicotine gum vs. placebo gum: comparisons of withdrawal symptoms and success rates, NIDA Research Monograph, 53, 83
  26. Schneider, 1983, Nicotine gum in smoking cessation: a placebo-controlled, double-blind trial, Addictive Behaviors, 8, 253, 10.1016/0306-4603(83)90020-5 · DOI
  27. Ferguson, 2012, Continuing to wear nicotine patches after smoking lapses promotes recovery of abstinence, Addiction (Abingdon, England), 107, 1349, 10.1111/j.1360-0443.2012.03801.x · DOI
  28. Shiffman, 2002, Efficacy of a nicotine lozenge for smoking cessation, Archives of Internal Medicine, 162, 1267, 10.1001/archinte.162.11.1267 · DOI · Paper page
  29. Shiffman, 2009, Quitting by gradual smoking reduction using nicotine gum: a randomized controlled trial, American Journal of Preventive Medicine, 36, 96, 10.1016/j.amepre.2008.09.039 · DOI
  30. Mikkelsen, 1994, Three-year outcome of two- and three-year sustained abstainers from a smoking cessation study with nicotine patches, Journal of Smoking-Related Disorders, 5, 95
  31. Tønnesen, 1992, Two-year outcome in a smoking cessation trial with a nicotine patch, Journal of Smoking-Related Disorders, 3, 241
  32. Villa, 1999, Effectiveness of a multicomponent program to quit smoking with and without nicotine chewing gum, Psicologia Conductual, 7, 107
  33. Pharmacia, 1998, Nicorette Nicotine Microtab Monograph, Adis Internatio
  34. Ben Taleb, 2017, Smoking cessation and changes in body mass index: Findings from the first randomized cessation trial in a low-income country setting, Nicotine & Tobacco Research, 19, 351
  35. Bolliger, 2002, Influence of long-term smoking reduction on health risk markers and quality of life, Nicotine & Tobacco Research, 4, 433, 10.1080/1462220021000018380 · DOI
  36. Bolliger, 2000, Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety, BMJ, 321, 329, 10.1136/bmj.321.7257.329 · DOI
  37. Brantmark, 1973, Nicotine-containing chewing gum as an anti-smoking aid, Psychopharmacologia, 31, 191, 10.1007/BF00422509 · DOI
  38. Croghan, 2005, Comparing nicotine inhaler, bupropion and nicotine inhaler plus bupropion in treating tobacco dependence [abstract], Nicotine & Tobacco Research, 7, 680
  39. Glover ED Glover PN Sullivan CR Sullivan P Nilsson F Sawe U Nicotine inhaler versus placebo in smoking cessation [abstract 237] 8th World Conference on Tobacco or Health; 1992; Buenos Aires, Argentina 1992
  40. Haustein, 2003, The effect of short-term or long-term reduction on smoking cessation; results from a placebo controlled smoking reduction study with the nicotine gum, Nicotine & Tobacco Research, 5, 278
  41. Sonntag, 2003, Smoking cessation in primary care: implementation effectiveness and optimized allocation, Suchtmedizin in Forschung und Praxis, 5, 137
  42. Jarvik, 1984, Degree of addiction and effectiveness of nicotine gum therapy for smoking, American Journal of Psychiatry, 141, 790, 10.1176/ajp.141.6.790 · DOI
  43. Kozak, 1995, High-dose treatment with the nicotine patch, International Journal of Smoking Cessation, 4, 26
  44. Krumpe, 1989, Efficacy of transdermal nicotine administration as an adjunct for smoking cessation in heavily nicotine addicted smokers, Annual Review of Respiratory Disease, 139, A337
  45. Landfeldt, 1998, Nicotine replacement treatment in heavy smokers: nicotine nasal spray combined with nicotine patch in a double-blind controlled study (abstract), European Respiratory Journal, 12, 154S
  46. Meier Lammermann, 1990, Combination of transdermal nicotine substitution and behavioural group therapy in smoking cessation, European Respiratory Journal, 3, 168S
  47. Rennard, 2002, Efficacy of nicotine inhaler in smoking reduction, Nicotine & Tobacco Research, 4, 380
  48. Ferguson, 2012, Continuing to wear nicotine patches after smoking lapses promotes recovery of abstinence, Addiction, 107, 1349, 10.1111/j.1360-0443.2012.03801.x · DOI
  49. Shiffman S Dresler CM Gorsline J Dimarino ME The efficacy of nicotine patch in an over-the-counter environment: results from a randomized, double-blind, placebo-controlled trial (PO130) 11th World Conference on Tobacco or Health; 2000 August 06-11; Chicago, Illinois, USA 2000
  50. Sutherland, 1999, A placebo-controlled double-blind combination trial of nicotine spray and patch [abstract], Nicotine & Tobacco Research, 1, 186
  51. Uyar, 2005, Comparison of nicotine patch and bupropion in treating tobacco dependence, European Respiratory Journal, 26, 388s
  52. Vikhireva O Shalnova S Deev A Nicotine replacement therapy in Russia: old wine in new skins? Randomized parallel study of nicotine gum/inhaler in smoking cessation/reduction Society for Research on Nicotine and Tobacco. 5th European Conference; 2003 November 20-22; Padua, Italy 2003
  53. Wennike, 2003, Smoking reduction promotes smoking cessation: results from a double blind, randomized, placebo-controlled trial of nicotine gum with 2-year follow-up, Addiction, 98, 1395, 10.1046/j.1360-0443.2003.00489.x · DOI · Paper page
  54. Clavel, 1984, Tobacco withdrawal. Comparison of the efficacy of various methods. Intermediate results of a comparative study, Presse Médicale, 13, 975
  55. Daughton, 1999, The smoking cessation efficacy of varying doses of nicotine patch delivery systems 4 to 5 years post-quit day, Preventive Medicine, 28, 113, 10.1006/pmed.1998.0391 · DOI
  56. Deeks JJ Higgins JPT Altman DG editor(s) on behalf of the Cochrane Statistical Methods Group Chapter 9: Analysing data and undertaking meta-analyses. in: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration Available from handbook.cochrane.org
  57. Durcan, 2002, Impact of prior nicotine replacement therapy on smoking cessation efficacy, American Journal of Health Behaviors, 26, 213, 10.5993/AJHB.26.3.6 · DOI
  58. Fagerström, 2003, Clinical treatment of tobacco dependence: The endurance of pharmacologic efficacy, Journal of Clinical Psychiatry Monograph, 18, 35
  59. Osservatorio, 2004, Linee Guida Cliniche per Promuovere la Cessazione dell’Abitudine al Fumo
  60. Jensen, 1990, Effect of nicotine, silver acetate, and ordinary chewing gum in combination with group counselling on smoking cessation, Thorax, 45, 831, 10.1136/thx.45.11.831 · DOI
  61. Joseph, 1999, Lack of efficacy of transdermal nicotine in smoking cessation, New England Journal of Medicine, 341, 1157, 10.1056/NEJM199910073411514 · DOI
  62. Mikkelsen, 1994, Three-year outcome of two- and three-year sustained abstainers from a smoking cessation study with nicotine patches, Journal of Smoking-Related Disorders, 5, 95
  63. Muller, 1990, The use of transdermal nicotine in smoking cessation, Lung, 168, 445, 10.1007/BF02718163 · DOI
  64. National Institute for Health and Clinical Excellence, 2008, Public Health Guideline [PH10] Stop Smoking Services
  65. Ministry of Health, 2014, The New Zealand Guidelines for Helping People to Stop Smoking.
  66. Ockene, 1994, The physician-delivered smoking intervention project: can short-term interventions produce long-term effects for a general outpatient population?, Health Psychology, 13, 278, 10.1037/0278-6133.13.3.278 · DOI · Paper page
  67. Richmond, 1997, Effectiveness of a 24-hour transdermal nicotine patch in conjunction with a cognitive behavioural programme: One year outcome, Addiction, 92, 27
  68. Schneider, 1983, Nicotine gum in smoking cessation: a placebo-controlled, double-blind trial, Addictive Behaviors, 8, 253, 10.1016/0306-4603(83)90020-5 · DOI
  69. Stapleton, 1998, How much does relapse after one year erode effectiveness of smoking cessation treatments? Long term follow up of randomised trial of nicotine nasal spray, BMJ, 316, 830, 10.1136/bmj.316.7134.830 · DOI
  70. Transdermal Nicotine Working Group, 1994, Nicotine replacement therapy for patients with coronary artery disease. Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease, Archives of Internal Medicine, 154, 989, 10.1001/archinte.1994.00420090063007 · DOI
  71. Tønnesen, 1992, Two-year outcome in a smoking cessation trial with a nicotine patch, Journal of Smoking-Related Disorders, 3, 241
  72. Silagy, 1996, Nicotine replacement therapy for smoking cessation, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD000146 · DOI · Paper page
  73. Silagy, 2001, Nicotine replacement therapy for smoking cessation, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD000146 · DOI · Paper page
  74. Silagy, 2002, Nicotine replacement therapy for smoking cessation, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD000146 · DOI · Paper page

Cited by

Sorted by citations

See all 711

Related

See all

Metadata

Authors
Hartmann-Boyce, J., Chepkin, S. C., Ye, W., Bullen, C., & Lancaster, T.
Affiliations
  • University of Oxford; Nuffield Department of Primary Care Health Sciences; Radcliffe Observatory Quarter Woodstock Road Oxford UK OX2 6GG
  • Cochrane (GB)
  • University of Oxford (GB)
  • University of Auckland (NZ)
  • King's College London (GB)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2018-05-31
Volume
2019
Issue
1
Pages
CD000146-CD000146
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd000146.pub5
PMC
PMC6353172
OpenAlex
W2806909877
Cited by
697
References
423
Citations by year
2026: 41 · 2025: 74 · 2024: 119 · 2023: 104 · 2022: 100 · 2021: 118 · 2020: 74 · 2019: 52 · 2018: 13
FWCI
8.45
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
Funders
American Lung Association
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
Keywords
nicotine replacement therapy, smoking cessation, nicotine gum, nicotine patch, nicotine inhaler, nicotine lozenges, long-term abstinence, nicotine withdrawal symptoms, adverse events, risk of bias, tobacco control, tobacco advertising restrictions
MeSH terms
Smoking Prevention, Administration, Cutaneous, Administration, Inhalation, Chewing Gum, Female, Humans, Male, Nicotine, Tablets, Time Factors, Randomized Controlled Trials as Topic, Smoking Cessation, Nicotinic Agonists, Tobacco Use Cessation Devices

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review