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September 28, 2023

4 min read

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Key takeaways:

  • The greatest likelihood for smoking cessation was found with e-cigarettes, varenicline, cytisine or combination nicotine replacement therapy.
  • Few serious adverse events occurred with these interventions.

Among various smoking cessation therapies, the highest likelihood for quitting was found with use of e-cigarettes, varenicline or cytisine, according to results published in Cochrane Database of Systematic Reviews.

Cigarette smokers also had similarly improved chances of quitting with use of a nicotine patch paired with a fast-acting form of nicotine replacement therapy (NRT), according to researchers.

Infographic showing odds for quitting cigarettes compared with a control.

Data were derived from Lindson N, et al. Cochrane Database Syst Rev. 2023;doi:10.1002/14651858.CD015226.pub2.

Nicola Lindson

“This study can help clinicians to make informed choices about the treatments they offer patients and enable them to inform patients about the options that will give them the best chances of quitting smoking,” Nicola Lindson, PhD, CPsychol, senior researcher in the Nuffield Department of Primary Care Health Sciences at the University of Oxford, told Healio.

“In many places cytisine and varenicline are not currently available and in those cases, clinicians can act on the knowledge that e-cigarettes closely followed by using two forms of nicotine replacement therapy together (a nicotine patch plus another form, such as gum or lozenge) are likely to provide the best chances of success,” Lindson added. “Where varenicline and cytisine are available this provides even more potential options. Having a range of options available is important as for many who smoke it can take a number of attempts to quit successfully. This review provides further justification for both varenicline and cytisine to become more widely available as soon as possible.”

Using studies from Cochrane Reviews, Lindson and colleagues evaluated 319 randomized controlled trials (RCTs), cluster-RCTs or factorial RCTs that included 157,179 participants and reported on rates of 6-month smoking cessation or longer to determine which smoking cessation intervention (varenicline, cytisine, nortriptyline, bupropion, NRT and e-cigarettes) is linked to the highest prevalence of quitting, as well as the smallest number of serious adverse events using Bayesian component network meta-analyses. The studies compared these interventions with a control group consisting of no therapy, placebo or another approved pharmacotherapy.

For more than half of the studies, researchers could not make a clear judgement on the risk of bias; however, 51 studies were deemed low risk and 104 were deemed high risk. Notably, 118 studies received funding from the pharmaceutical or e-cigarette/tobacco industry; however, an analysis removing these studies resulted in the same conclusions, Lindson told Healio.

Quit rates

Compared with a control group, researchers reported high-certainty evidence of increased odds for quitting with three different cessation therapies: nicotine e-cigarettes (OR = 2.37; 95% credible interval [Crl], 1.73-3.24) in 16 RCTs (n = 3,828), varenicline (OR = 2.33; 95% Crl, 2.02-2.68) in 67 RCTs (n = 16,430) and cytisine (OR = 2.21; 95% Crl, 1.66-2.97) in seven RCTs (n = 3,848).

These findings suggest that use of e-cigarettes or varenicline will result in an additional eight quitters per 100, and use of cytisine will result in an extra seven quitters per 100.

“Finding that e-cigarettes, varenicline and cytisine are likely to have comparable effects on quitting smoking was not necessarily surprising but it is great to have some confirmation of what we suspected,” Lindson told Healio.

Use of a patch with a fast-acting form of NRT was also linked to higher odds for quitting (OR = 1.93; 95% Crl, 1.61-2.34), according to researchers.

Although not as high as those observed with e-cigarettes, varenicline, cytisine and two forms of NRT used together, researchers found high certainty evidence of elevated odds for quitting among people who used nicotine patch only (OR = 1.37; 95% Crl, 1.2-1.56) in 105 RCTs (n = 37,319), fasting-acting NRT only (OR = 1.41; 95% Crl, 1.29-1.55) in 120 RCTs (n = 31,756) and bupropion (OR = 1.43; 95% Crl, 1.26-1.62) in 71 RCTs (n = 14,759) vs. controls.

Per 100 people, use of fasting-acting NRT alone or bupropion meant an additional three quitters, whereas use of a nicotine patch alone meant an additional two quitters, according to researchers.

Researchers could only find moderate-certainty evidence for nortriptyline, but in the 10 RCTs assessed (n = 1,290), it was linked to a greater likelihood for quitting vs. a control (OR = 1.35; 95% Crl, 1.02-1.81).

Researchers found low-certainty evidence of quit rates with the use of non-nicotine/placebo e-cigarettes (OR = 1.16; 95% Crl, 0.74-1.8) in eight RCTs (n = 1,094), as well as with tapering a NRT dose before ending treatment (OR = 1.14; 95% Crl, 1-1.29) in 111 RCTs (n = 33,156).

Serious adverse events

In terms of serious adverse events, researchers found an overall low rate among all cessation treatments. Nortriptyline and non-nicotine e-cigarettes could not be included in this analysis due to a lack of data.

A comparable rate of serious adverse events was found between those using nicotine e-cigarettes, varenicline, cytisine or NRT and those using a placebo or no pharmacotherapy/e-cigarettes; however, this evidence was judged as low certainty by researchers.

Further, researchers found moderate-certainty evidence suggesting a possibility of slightly more serious adverse events with bupropion.

“We hope that future studies will collect more data on serious health effects of treatments over longer periods,” Lindson told Healio. “In particular we think these future studies should focus on directly comparing the most effective treatments: varenicline, cytisine, nicotine e-cigarettes and combination NRT. More research should be conducted on using these interventions in combination with one another, for example using e-cigarettes alongside varenicline or cytisine, and looking at the most effective ways to use these treatments, ie, the optimum nicotine concentration and device types for e-cigarettes.”

For more information:

Nicola Lindson, PhD, CPsychol, can be reached at




The National Institute for Health Research, via Cochrane Infrastructure and Cochrane Programme Grant funding to the Cochrane Tobacco Addiction Group supported this project. Lindson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.