EvidenceAlerts

RATIONALE: There is limited guidance on how to stop using nicotine-containing vapes (otherwise known as e-cigarettes) and ensure long-term abstinence, whilst minimising the risk of tobacco smoking and other unintended consequences. Treatments could include pharmacological interventions, behavioural interventions, or both.

OBJECTIVES: To conduct a living systematic review assessing the benefits and harms of interventions to help people stop vaping compared to each other, placebo or no intervention. To assess how these interventions affect the use of combustible tobacco, and whether effects vary based on participant characteristics.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from 1 January 2004 to 1 July 2025. We also searched the references of eligible studies and abstracts from the Society for Research on Nicotine and Tobacco conferences, and contacted study authors.

ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) recruiting people of any age using nicotine-containing vapes, regardless of tobacco smoking status. Studies had to test an intervention designed to support people to quit vaping, and plan to measure at least one of our outcomes.

OUTCOMES: Critical outcomes: vaping cessation at six months or longer; change in combustible tobacco use at six months or longer; number of participants reporting serious adverse events (SAEs) at one week or longer.

RISK OF BIAS: We used Cochrane's RoB 1 tool to assess risk of bias in the included studies.

SYNTHESIS METHODS: We followed standard Cochrane methods. We grouped studies by comparisons and outcomes, and calculated individual study and pooled effects, as appropriate. We used random-effects Mantel-Haenszel methods to calculate risk ratios (RRs) with 95% confidence intervals (CIs) and random-effects inverse variance methods to calculate mean differences (MDs) and 95% CIs. We used GRADE to assess the certainty of evidence for our critical outcomes.

INCLUDED STUDIES: Fifteen studies (six new to this updated version) involving 5800 participants are included. Fourteen studies included some participants who had previously smoked tobacco; in seven studies, participants were not smoking at baseline. Twelve studies only included participants aged 18 or older (five exclusively included people between 18 and 29); two included some participants under 18 years; and one included 13- to 17-year-olds only. Fourteen studies were conducted in the USA and one in Italy. We judged five studies at low, six at high, and four at unclear risk of bias.

SYNTHESIS OF RESULTS: Pharmacological interventions Studies assessed our critical outcomes in relation to combination nicotine replacement therapy (NRT), cytisine, and varenicline compared to placebo or no/minimal support. For combination NRT versus no/minimal support, there was no clear evidence of benefit for vaping cessation rates at six months or longer, with the CI incorporating the possibility of reduced and increased cessation rates (very low-certainty evidence due to imprecision and risk of bias; RR 0.96, 95% CI 0.73 to 1.25; I² = 0%; 2 studies, 214 participants). One study investigating cytisine versus placebo did not report vaping cessation at six months or longer. When compared to placebo, varenicline increased vaping cessation rates at six months, but evidence was of low certainty due to imprecision (RR 2.71, 95% CI 1.33 to 5.49; I2 = 48%; 2 studies, 315 participants). One study comparing combination NRT versus no/minimal support reported combustible tobacco cessation. There was no clear evidence of higher tobacco cessation in either arm, and CIs were imprecise. The evidence was of very low certainty due to imprecision and risk of bias (RR 0.99, 95% CI 0.71 to 1.37; 198 participants). Zero participants reported SAEs in the two studies investigating combination NRT versus no/minimal support (706 participants; very low-certainty evidence due to risk of bias and imprecision) and in the one study investigating cytisine versus placebo (159 participants; low-certainty evidence due to imprecision). Four studies evaluating varenicline versus placebo measured SAEs, with zero events reported in two studies. Thus, our effect estimate was based on two studies (RR 2.82, 95% CI 0.45 to 17.59; 304 participants; low-certainty evidence due to imprecision). Behavioural interventions Studies assessed our critical outcomes in relation to reducing nicotine/vaping behaviour and text message-based interventions compared to no/minimal support. There was no clear evidence that nicotine/vaping reduction increased vaping cessation at six months compared to minimal support (RR 3.38, 95% CI 0.43 to 26.30; 1 study, 17 participants; very low-certainty evidence due to imprecision and risk of bias). There was low-certainty evidence (due to indirectness) that text message-based interventions may increase vaping cessation rates compared to no/minimal support in 13- to 24-year-olds specifically (RR 1.32, 95% CI 1.19 to 1.47; I2 = 0%; 2 studies, 4091 participants). There was very low-certainty evidence (due to indirectness and imprecision) that text message-based interventions for vaping cessation may result in little to no difference in smoking uptake (RR 1.04, 95% CI 0.81 to 1.33; 1 study, 1036 participants) or cessation (RR 1.03, 95% CI 0.90 to 1.19; 1 study, 793 participants) compared to no/minimal support. The one study investigating nicotine/vaping behaviour reduction versus minimal support did not report SAEs. Three studies investigating text message-based interventions reported SAEs; however, zero events were reported (2082 participants; low-certainty evidence due to imprecision).

AUTHORS' CONCLUSIONS: Low-certainty evidence suggests that text message-based interventions to help people stop nicotine vaping may help more youths and young adults to successfully stop compared to no/minimal support, with very uncertain evidence regarding their effect on smoking behaviours. Low-certainty evidence suggests that varenicline may help people quit vaping. Data exploring the effectiveness of combination NRT, cytisine, and nicotine/vaping behaviour reduction are inconclusive due to risk of bias and imprecision. Most studies that measured SAEs reported that none had occurred; however, more data are needed to draw clear conclusions. Studies that have investigated these interventions for quitting smoking have not demonstrated serious concerns about SAEs. It is important that future studies measure combustible tobacco outcomes so the complete risk profile of relevant interventions can be considered. Further RCTs are underway. To ensure this review continues to provide up-to-date information to decision-makers, we will maintain it as a living systematic review by running searches monthly and updating the review when relevant new evidence that will strengthen or change our conclusions emerges.

FUNDING: Cancer Research UK (PICCTR-2024/100012); National Institute for Health and Care Research (NIHR206123).

REGISTRATION: Protocol (2024) DOI: 10.1002/14651858.CD016058 Original review (2025) DOI: 10.1002/14651858.CD016058.pub2.

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