Varenicline for e-cigarette (vaping) cessation: Systematic review and meta-analysis of randomized controlled trials

E-cigarette cessation is a critical public health priority, yet few evidence-based pharmacological interventions are available. Varenicline shows potential for this indication. This systematic review and meta-analysis evaluated the efficacy, safety, tolerability, and acceptability of varenicline for e-cigarette cessation.

This review included randomized controlled trials (RCTs) comparing varenicline with placebo in adolescents and adults using e-cigarettes daily or nearly daily. Primary outcomes were e-cigarette abstinence rates. Secondary outcomes included overall dropout, adverse-effect dropout, and the incidence of four common adverse events (nausea, insomnia, vivid dreams, and headache). Database searches extended through June 11, 2025. A random-effects model pooled the event rates. The analysis synthesized the incidence rates of adverse events using logit transformation and pooled them using a generalized linear mixed model.

Three RCTs (N = 355) compared varenicline with placebo over 8-12 weeks. No trial showed a high risk of bias. Varenicline significantly increased 7-day point prevalence abstinence (RR = 2.28; 95% CI = 1.68-3.09; I² = 0.0%) and continuous abstinence rates (RR = 2.71; 95% CI = 1.48-4.97; I² = 57.7%) compared with placebo. Overall dropout rates showed no significant difference between groups (RR = 0.81; 95% CI = 0.44-1.49; I² = 1.1%). Adverse-effect dropout rates and headache incidence did not differ significantly. Varenicline was associated with significantly higher rates of nausea (RR = 2.42; 95% CI = 1.82-3.21; I² = 18.3%), insomnia (RR = 1.96; 95% CI = 1.32-2.91; I² = 0.0%), and vivid dreams (RR = 2.64; 95% CI = 1.66-4.18; I² = 0.0%) than placebo. Among varenicline recipients, nausea was the most common adverse event (61%; 95% CI = 0.51%-0.70%; I² = 58.1%), followed by insomnia, vivid dreams, and headache.

In adults, varenicline appears effective, well-tolerated, and acceptable for e-cigarette cessation and may also apply to adolescent populations. Although nausea, insomnia, and vivid dreams occur more often with varenicline, these adverse events are generally mild and rarely lead to treatment discontinuation. These findings remain preliminary due to the small samples and limited number of studies.