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nicotine replacement therapy for smokers

NIHR Signal Using both nicotine patches and gum together improves the chances of quitting smoking

Published on 1 July 2019

doi: 10.3310/signal-000786

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.  

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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.

Bibliography

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.

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.

Bibliography

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.

Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation

Published on 18 April 2019

N Lindson, S ChepkinWeiyu Ye, T FanshaweC Bullen, J Hartmann‐Boyce

Cochrane Database of Systematic Reviews , 2019

Background Nicotine replacement therapy (NRT) aims to replace nicotine from cigarettes to ease the transition from cigarette smoking to abstinence. It works by reducing the intensity of craving and withdrawal symptoms. Although there is clear evidence that NRT used after smoking cessation is effective, it is unclear whether higher doses, longer durations of treatment, or using NRT before cessation add to its effectiveness. Objectives To determine the effectiveness and safety of different forms, deliveries, doses, durations and schedules of NRT, for achieving long‐term smoking cessation, compared to one another. Search methods We searched the Cochrane Tobacco Addiction Group trials register, and trial registries for papers mentioning NRT in the title, abstract or keywords. Date of most recent search: April 2018. Selection criteria Randomized trials in people motivated to quit, comparing one type of NRT use with another. We excluded trials that did not assess cessation as an outcome, with follow‐up less than six months, and with additional intervention components not matched between arms. Trials comparing NRT to control, and trials comparing NRT to other pharmacotherapies, are covered elsewhere. Data collection and analysis We followed standard Cochrane methods. Smoking abstinence was measured after at least six months, using the most rigorous definition available. We extracted data on cardiac adverse events (AEs), serious adverse events (SAEs), and study withdrawals due to treatment. We calculated the risk ratio (RR) and the 95% confidence interval (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta‐analyses where appropriate, using a Mantel‐Haenszel fixed‐effect model. Main results We identified 63 trials with 41,509 participants. Most recruited adults either from the community or from healthcare clinics. People enrolled in the studies typically smoked at least 15 cigarettes a day. We judged 24 of the 63 studies to be at high risk of bias, but restricting the analysis only to those studies at low or unclear risk of bias did not significantly alter results, apart from in the case of the preloading comparison. There is high‐certainty evidence that combination NRT (fast‐acting form + patch) results in higher long‐term quit rates than single form (RR 1.25, 95% CI 1.15 to 1.36, 14 studies, 11,356 participants; I2 = 4%). Moderate‐certainty evidence, limited by imprecision, indicates that 42/44 mg are as effective as 21/22 mg (24‐hour) patches (RR 1.09, 95% CI 0.93 to 1.29, 5 studies, 1655 participants; I2 = 38%), and that 21 mg are more effective than 14 mg (24‐hour) patches (RR 1.48, 95% CI 1.06 to 2.08, 1 study, 537 participants). Moderate‐certainty evidence (again limited by imprecision) also suggests a benefit of 25 mg over 15 mg (16‐hour) patches, but the lower limit of the CI encompassed no difference (RR 1.19, 95% CI 1.00 to 1.41, 3 studies, 3446 participants; I2 = 0%). Five studies comparing 4 mg gum to 2 mg gum found a benefit of the higher dose (RR 1.43, 95% CI 1.12 to 1.83, 5 studies, 856 participants; I2 = 63%); however, results of a subgroup analysis suggest that only smokers who are highly dependent may benefit. Nine studies tested the effect of using NRT prior to quit day (preloading) in comparison to using it from quit day onward; there was moderate‐certainty evidence, limited by risk of bias, of a favourable effect of preloading on abstinence (RR 1.25, 95% CI 1.08 to 1.44, 9 studies, 4395 participants; I2 = 0%). High‐certainty evidence from eight studies suggests that using either a form of fast‐acting NRT or a nicotine patch results in similar long‐term quit rates (RR 0.90, 95% CI 0.77 to 1.05, 8 studies, 3319 participants; I2 = 0%). We found no evidence of an effect of duration of nicotine patch use (low‐certainty evidence); 16‐hour versus 24‐hour daily patch use; duration of combination NRT use (low‐ and very low‐certainty evidence); tapering of patch dose versus abrupt patch cessation; fast‐acting NRT type (very low‐certainty evidence); duration of nicotine gum use; ad lib versus fixed dosing of fast‐acting NRT; free versus purchased NRT; length of provision of free NRT; ceasing versus continuing patch use on lapse; and participant‐ versus clinician‐selected NRT. However, in most cases these findings are based on very low‐ or low‐certainty evidence, and are the findings from single studies. AEs, SAEs and withdrawals due to treatment were all measured variably and infrequently across studies, resulting in low‐ or very low‐certainty evidence for all comparisons. Most comparisons found no evidence of an effect on cardiac AEs, SAEs or withdrawals. Rates of these were low overall. Significantly more withdrawals due to treatment were reported in participants using nasal spray in comparison to patch in one trial (RR 3.47, 95% CI 1.15 to 10.46, 922 participants; very low certainty) and in participants using 42/44 mg patches in comparison to 21/22 mg patches across two trials (RR 4.99, 95% CI 1.60 to 15.50, 2 studies, 544 participants; I2 = 0%; low certainty). Authors' conclusions There is high‐certainty evidence that using combination NRT versus single‐form NRT, and 4 mg versus 2 mg nicotine gum, can increase the chances of successfully stopping smoking. For patch dose comparisons, evidence was of moderate certainty, due to imprecision. Twenty‐one mg patches resulted in higher quit rates than 14 mg (24‐hour) patches, and using 25 mg patches resulted in higher quit rates than using 15 mg (16‐hour) patches, although in the latter case the CI included one. There was no clear evidence of superiority for 42/44 mg over 21/22 mg (24‐hour) patches. Using a fast‐acting form of NRT, such as gum or lozenge, resulted in similar quit rates to nicotine patches. There is moderate‐certainty evidence that using NRT prior to quitting may improve quit rates versus using it from quit date only; however, further research is needed to ensure the robustness of this finding. Evidence for the comparative safety and tolerability of different types of NRT use is of low and very low certainty. New studies should ensure that AEs, SAEs and withdrawals due to treatment are both measured and reported.

Expert commentary

This review summarised 63 trials, including 41,509 participants. There was moderate quality evidence that higher dose nicotine patches were more effective than moderate dose patches, but no evidence that double dose patches were more effective.

Likewise, there was moderate quality evidence that higher dose gum was more effective, but perhaps only for more dependent smokers. There was high quality evidence that using two forms of nicotine replacement, patch plus a short-acting form together, was more effective than a single form. There was also moderate quality evidence that using NRT before attempting to stop smoking improved abstinence.

When it comes to nicotine replacement, more is generally more effective.

Paul Aveyard, Professor of Behavioural Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford

The commentator is the editor of the Cochrane Tobacco Addiction Group, which includes this review

Author commentary

Though many people use nicotine replacement therapies to try to quit smoking, few are using it to its best effect, which reduces their chances of quitting.

This review sends a clear message for healthcare professionals and people trying to quit smoking – namely, that a combination of patch and fast-acting form of nicotine replacement such as gum, nasal spray, or lozenge, increases chances of successfully quitting compared to using only one kind.

Nicotine replacement is generally considered safe, and evidence from this review does not indicate an increased risk of harms from using two forms at the same time.

Jamie Hartmann-Boyce, Senior Researcher (Health Behaviours and Cochrane Tobacco Addiction Group), Nuffield Department of Primary Care Health Sciences, University of Oxford

The commentator is an author of the review