Using a combination of nicotine patches together with another type of nicotine replacement therapy (NRT) (such as gum or lozenge) is more likely to help people quit smoking than if they used one type of NRT alone. We also found that people who smoke have the same chance of quitting successfully whether they use a nicotine patch or another type of NRT, such as gum, lozenge or nasal spray.
More high-quality studies on different NRT patch doses, durations of NRT use, types of fast-acting NRT, and NRT use prior to quit day are needed to know which treatments work best to help people quit smoking. These studies should report safety outcomes and withdrawals due to treatment.
What is nicotine replacement therapy?
Nicotine replacement therapy (NRT) is a medicine that delivers nicotine to the brain. It is available as skin patches, chewing gum, nasal and oral sprays, inhalers, lozenges and tablets. The aim of NRT is to replace the nicotine that people who smoke usually get from cigarettes, so the urge to smoke is reduced and they can stop smoking completely. We know that NRT improves a person's chances of stopping smoking, and that people use it to quit.
What did we want to find out?
NRT can be taken in many different forms, in different doses and for varying amounts of time. Some people start using NRT before they quit, while other people wait until quit day. This review looks at the different forms, doses, durations and schedules of NRT used to help people quit smoking, so we can better understand which of these work best to help people quit smoking for six months or longer. We also wanted to find out if any of these treatments were associated with cardiac (heart-related) or serious unwanted effects, and if anyone stopped participating in a study due to the NRT treatment they were advised to use.
What did we do?
We searched for studies that looked at the use of NRT to help people quit smoking and that followed people up for at least six months.
What we found
We found 68 completed studies conducted in 43,327 participants. Most participants were adults who wanted to quit smoking.
People who smoke have the same chances of quitting successfully whether they use a nicotine patch to quit or another type of NRT, such as gum, lozenge or nasal spray. Using nicotine patches together with another type of NRT (such as gum or lozenge) made it 17% to 37% more likely that a person would successfully stop smoking than if they used one type of NRT alone.
People who used higher-dose nicotine patches (25 mg patches worn for 16 hours, or 21 mg patches worn for 24 hours) were more likely to quit smoking compared to those using lower-dose patches (15 mg patches worn for 16 hours or 14 mg patches worn for 24 hours). However, there was not any clear evidence to suggest that people using 42 mg or 44 mg patches were more likely to quit than people using 21 mg or 22 mg (24-hour) patches.
Starting to use NRT before a quit day may help more people to quit than only using it after a quit day, but more evidence is needed to strengthen this conclusion.
We also looked at how long NRT should be used for, whether NRT should be used on a schedule or on demand as craved, and whether more people stop smoking when NRT is provided for free versus if they have to pay for it. More research is needed to answer these questions.
Most studies did not look at the safety of NRT. Where studies did look at safety, they found that very few people experienced negative effects.
How reliable are these results?
There is high-certainty evidence that:
- combination NRT works better than a single form of NRT; and
- there is no difference in effect between different types of NRT (such as gum or patch).
This means that future research is very unlikely to change our conclusions. This is because the evidence is based on many participants and on well-conducted studies.
However, the certainty of the evidence was moderate, low or very low for all the other questions we considered. This means that our findings may change as new research is carried out. In most cases, this is because there were not enough studies, there were problems with the design of studies that do exist, and/or these studies were too small.
In terms of the safety of different ways of using NRT, we rated the evidence for this outcome to be of low or very low certainty because many studies did not report on safety. Large studies covered in a separate review show high-certainty evidence that NRT is safe to use for quitting smoking.
How up to date is this evidence?
This review updates our previous review. The evidence is up to date to April 2022.
There is high-certainty evidence that using combination NRT versus single-form NRT and 4 mg versus 2 mg nicotine gum can result in an increase in the chances of successfully stopping smoking. Due to imprecision, evidence was of moderate certainty for patch dose comparisons. There is some indication that the lower-dose nicotine patches and gum may be less effective than higher-dose products. 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 before 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 limited. New studies should ensure that AEs, SAEs and withdrawals due to treatment are reported.
Nicotine replacement therapy (NRT) aims to replace nicotine from cigarettes. This helps to reduce cravings and withdrawal symptoms, and ease the transition from cigarette smoking to complete abstinence. Although there is high-certainty evidence that NRT is effective for achieving long-term smoking abstinence, it is unclear whether different forms, doses, durations of treatment or timing of use impacts its effects.
To determine the effectiveness and safety of different forms, deliveries, doses, durations and schedules of NRT, for achieving long-term smoking cessation.
We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning NRT in the title, abstract or keywords, most recently in April 2022.
We included randomised trials in people motivated to quit, comparing one type of NRT use with another. We excluded studies that did not assess cessation as an outcome, with follow-up of fewer than six months, and with additional intervention components not matched between arms. Separate reviews cover studies comparing NRT to control, or to other pharmacotherapies.
We followed standard Cochrane methods. We measured smoking abstinence 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 identified 68 completed studies with 43,327 participants, five of which are new to this update. Most completed studies recruited adults either from the community or from healthcare clinics. We judged 28 of the 68 studies to be at high risk of bias. Restricting the analysis only to those studies at low or unclear risk of bias did not significantly alter results for any comparisons apart from the preloading comparison, which tested the effect of using NRT prior to quit day whilst still smoking.
There is high-certainty evidence that combination NRT (fast-acting form plus patch) results in higher long-term quit rates than single form (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.17 to 1.37; I2 = 12%; 16 studies, 12,169 participants). Moderate-certainty evidence, limited by imprecision, indicates that 42/44 mg patches are as effective as 21/22 mg (24-hour) patches (RR 1.09, 95% CI 0.93 to 1.29; I2 = 38%; 5 studies, 1655 participants), and that 21 mg patches 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; I2 = 0%; 3 studies, 3446 participants).
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; I2 = 0%; 9 studies, 4395 participants).
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; I2 = 0%; 8 studies, 3319 participants).
We found no clear evidence of an effect of duration of nicotine patch use (low-certainty evidence); duration of combination NRT use (low- and very low-certainty evidence); or fast-acting NRT type (very low-certainty evidence).
Cardiac 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 clear evidence of an effect on these outcomes, and rates were low overall. More withdrawals due to treatment were reported in people using nasal spray compared to patches in one study (RR 3.47, 95% CI 1.15 to 10.46; 1 study, 922 participants; very low-certainty evidence) and in people using 42/44 mg patches in comparison to 21/22 mg patches across two studies (RR 4.99, 95% CI 1.60 to 15.50; I2 = 0%; 2 studies, 544 participants; low-certainty evidence).