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

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
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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.

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Crossref · 10.1002/14651858.cd000146.pub5

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  • There was evidence of an association between the use of nicotine replacement therapy and smoking abstinence at 6 months or more, with pooled RR 1.55 (95% CI, 1.49 to 1.61; 133 trials; n=64,640) compared with placebo or no drug.

    “The pooled RR for abstinence for NRT was 1.55 (95% CI, 1.49 to 1.61; 133 trials; n=64,640);[27](#R27)”

    From Interventions for Tobacco Cessation in Adults, Including Pregnant Persons (2021) · cites this paper as [27]

    The Summary of findings reports an RR of 1.55 (95% CI 1.49 to 1.61) for abstinence at six months or longer, comparing NRT with placebo or no NRT, among 64,640 participants. It reports 131 trials and 133 comparisons, not 133 trials as the citing sentence states. (LLM, conf=0.92)

    Experimental — accuracy not yet measured

  • The various types of nicotine replacement have comparable effectiveness, with 17% quit rates at 6 months, compared to 10% for placebo.

    “The various types have comparable effec tiveness, with 17% quit rates at 6 months, compared to 10% for placebo 174 .”

    From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [174]

    The Authors’ Conclusions (page unavailable) say that the form of NRT delivery is unrelated to effectiveness. The Summary of Findings (page unavailable) reports increased cessation with every form of NRT at six months or longer, but the passages found do not establish 17% versus 10% quit rates at six months; the comparison also includes controls receiving no NRT, not only placebo. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Nine primary reviews reported adverse events related to pharmacotherapy interventions for smoking cessation in general adult populations.

    “Nine primary reviews reported adverse events (AEs) related to pharmacotherapy interventions for smoking cessation in general adult populations.[16](#R16),[18](#R18),[27](#R27),[29](#R29),[35](#R35),[44](#R44),[45](#R45),[59](#R59),[62](#R62)”

    From Interventions for Tobacco Cessation in Adults, Including Pregnant Persons (2021) · cites this paper as [27]

  • Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant smokers.

    “Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant smokers [3];”

    From Vaping during pregnancy: a systematic review of health outcomes. (2024) · cites this paper as [3]

  • Nicotine replacement therapy increases the rate of quitting by 50-60%, regardless of setting and NRT preparation.

    “NRT increases the rate of quitting by 50–60%, regardless of setting and NRT preparation (78).”

    From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [78]

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Research works printed but not linked: 4

  1. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2002, Issue 4. [DOI: 10.1002/14651858.CD000146] · DOI · Paper page
  2. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/14651858.CD000146] · DOI · Paper page
  3. Fergusson D, Glass KC, Waring D, Shapiro S. Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials. BMJ. 2004 Feb 21;328(7437):432 2004
  4. Tonnesen P, Norregaard J, Sawe U, Simonsen K. Recycling with nicotine patches in smoking cessation. Addiction. 1993 Apr;88(4):533-9

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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 · 2017: 1 · 2012: 1
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 › Physiology › 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

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