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Using a nicotine patch together with a fast-acting type of nicotine replacement therapy (NRT) such as gum or lozenges improves smoking cessation rates compared to using only a single type of NRT. Higher-dose nicotine patches are also more effective than lower dose ones, this NIHR-funded review suggests.

A previous Cochrane systematic review found that NRT boosts people’s chances of successfully quitting smoking compared to none, but it was unclear which types, doses and schedules were most effective. This review of 63 trials, involving over 40,000 cigarette smokers, compared the safety and effectiveness of different NRT regimens to help people become tobacco-free for at least six months.

They found that using combination NRT (patch + fast-acting form such as gum, lozenges or spray) increases the rate of successfully quitting by about 25%, compared with single form NRT (either a patch or a fast-acting form alone).

The finding supports NICE guidance on smoking cessation and harm reduction.

Why was this study needed?

Tobacco use is a leading preventable cause of death. It is estimated to have caused 77,900 deaths in England in 2016. Although most smokers would like to stop, doing so is complicated by psychological and physiological dependence on smoking and the nicotine found in tobacco.

NRT aims to ease the transition from cigarette smoking to abstinence. It reduces the intensity of craving and withdrawal symptoms by delivering nicotine via skin patches, chewing gum, nasal and oral sprays, inhalers, lozenges or tablets. Although there is clear evidence that NRT improves a person's chances of stopping smoking, it is unclear whether higher doses, longer durations of treatment, or initiating NRT before giving up smoking increases its effectiveness.

This review aimed to determine the effectiveness of different forms, deliveries, doses, durations and schedules of NRT for long‐term smoking cessation.

What did this study do?

This was a Cochrane systematic review of 63 randomised trials, comparing NRT regimens and their effectiveness for smoking cessation. It involved a total of 41,509 participants, recruited from the community or healthcare clinics and who typically smoked at least 15 cigarettes a day. Smoking abstinence was measured after at least six months, with those lost to follow-up assumed to be continuing to smoke.

Twenty-four of the studies were judged to be at high risk of bias, although restricting the analysis only to those at low or unclear risk of bias did not significantly alter the main results. Since this review only examined smokers who were motivated to quit and who smoked more than 15 cigarettes a day, it is unable to provide guidance on the role of nicotine replacement in lighter smokers.

Electronic cigarettes are not included in this review. Other Cochrane reviews compare NRT to other pharmacotherapies, and in specific populations such as pregnant women and adolescents.

What did it find?

  • There is strong evidence that combination NRT (patch + a fast‐acting form of NRT) increases the chance of long-term abstinence by about 25% compared with using a single form of NRT (risk ratio [RR] 1.25, 95% confidence interval [CI] 1.15 to 1.36; 14 studies, 11,356 participants). Interventions that included a single-form of NRT were successful for 14% of smokers, while combination NRT was successful for 17%.
  • People are more likely to successfully quit when they use higher doses of nicotine gum and nicotine patches.
  • Beginning to use NRT while still smoking appears to improve successful quitting, but risk of bias means more evidence would help to confirm this (RR 1.25, 95% CI 1.08 to 1.44; 9 studies, 4,395 participants).
  • The study found no differences in effectiveness between different forms of NRT used alone, and insufficient evidence about whether tapering was more effective than abruptly stopping NRT, or whether ad-lib or fixed-dosing of fast-acting NRT is better.
  • Severe adverse events associated with NRT are rare, and there is insufficient evidence on whether different regimens carry different risks.

What does current guidance say on this issue?

NICE 2018 guidelines advise that stop smoking services offer a range of behavioural support and pharmacotherapy for adults who smoke. People using NRT should start the day before the agreed quit date and be advised that a combination of short-acting and long-acting NRT is likely to be most effective.

A NICE 2013 public health guideline on harm reduction adds that people should be supported to use sufficiently high doses of NRT to control cravings and prevent compensatory smoking. NRT can be used for as long as it helps reduce the desire to smoke, and for the long term if necessary to prevent relapse. It also advises that people should be told that electronic cigarettes are not regulated and, although their safety and effectiveness cannot be assured, they are likely to be less harmful than cigarettes.

What are the implications?

Nicotine replacement therapy is an effective support for quitting smoking in those who are motivated to quit, and this review provides further guidance on how best to administer it.

Commissioners and providers of smoking cessation services should continue to offer a range of behavioural supports and pharmacotherapies in line with NICE guidance. This study supports that, where NRT is used, patients should be advised that a combination of both fast-release NRT (such as gums or lozenges) and slower-release patches together will increase their chances of quitting in the long-term. Additionally, use of higher dose formulations appears to be safe and more effective.

Citation and Funding

Lindson N, Chepkin SC, Ye W et al. Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2019;(4): CD013308.

Cochrane UK and the Tobacco Addiction Cochrane Review Group are supported by NIHR infrastructure funding.



Hartmann-Boyce J, Chepkin SC, Ye W et al. Can nicotine replacement therapy (NRT) help people quit smoking? Oxford: Cochrane Tobacco Addiction Review Group; 2018.

NHS Digital. Statistics on smoking – England 2018. Leeds: Department of Health and Social Care; 2018.

NICE. Stop smoking interventions and services. NG92. London: National Institute for Health and Care Excellence; 2018.

NICE. Smoking: harm reduction. PH45. London: National Institute for Health and Care Excellence; 2013.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre


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