Highlights
1. A pragmatic randomized controlled trial found no significant difference in 7-month continuous smoking abstinence at 9 months between e-cigarettes and combination nicotine replacement therapy (cNRT) among patients discharged from smoke-free inpatient substance use disorder withdrawal services.
2. Both interventions achieved approximately 10% continuous abstinence rates in a population with high tobacco-related morbidity and mortality.
3. Serious adverse events were low and similar between groups, with none attributable to treatment.
4. Secondary systematic review analysis reveals heterogeneity in longitudinal smoking abstinence trajectories and relapse patterns in e-cigarette cessation trials, highlighting instability of risk ratios over time and the need for further relapse-focused data.
Study Background and Disease Burden
Tobacco smoking remains a leading cause of preventable morbidity and mortality worldwide. Individuals with substance use disorders (SUDs) exhibit disproportionately high rates of tobacco use and related health complications, yet evidence-based smoking cessation strategies tailored for this population are limited. While nicotine-containing electronic cigarettes (e-cigarettes) have demonstrated efficacy for smoking cessation in the general population, their effectiveness and safety profile in people with SUDs remains under-investigated. Given the smoke-free policies in inpatient alcohol and drug withdrawal services, the transition period post-discharge represents a critical window for intervention to reduce tobacco use and its associated harms.
Study Design
The primary study was a pragmatic, two-arm, single-blinded, parallel-group randomized controlled trial conducted in Australia (ACTRN12619001787178). Adults admitted to five smoke-free inpatient withdrawal services who were motivated tobacco smokers but not current e-cigarette users were enrolled. Participants (n=363) were randomized 1:1 to receive either a 12-week supply of e-cigarettes or combination nicotine replacement therapy (cNRT) alongside Quitline behavioural counselling at discharge. Participants were encouraged to use the assigned cessation aid ad libitum. Outcomes were assessed primarily in the community setting post-discharge. The primary endpoint was 7 months continuous tobacco abstinence measured at 9 months after randomization. The analysis employed an intention-to-treat approach supplemented by sensitivity analyses. Serious adverse events (SAEs) were adjudicated for severity and causality.
Key Findings
In the trial, 179 participants received e-cigarettes and 184 received cNRT. At 9-month follow-up, continuous abstinence rates were 11% for e-cigarettes versus 10% for cNRT, with no statistically significant difference (risk ratio 1.09; 95% credible interval 0.52–1.89). The probability of a positive treatment effect was low (Bayes factor 0.04). SAEs were infrequent and balanced between groups (15 in e-cigarette arm vs. 13 in cNRT; incident rate ratio 1.18; p=0.65), with none attributed to treatment. These cessation rates and safety profiles are notable given the challenges in treating tobacco dependence within SUD populations, who face higher relapse risks and tobacco-related health burdens.
Complementing this, a secondary analysis of 15 randomized trials involving 7233 participants assessed longitudinal patterns of smoking abstinence in e-cigarette cessation studies. Continuous abstinence rates generally declined over time but with variable slopes across studies. Point prevalence abstinence showed heterogeneous trajectories, including both declines and increases over time. Relative abstinence rates comparing e-cigarettes with control arms were inconsistent across studies and timepoints. Moreover, relapse data, though sparse, indicated heterogeneous demographic and behavioral predictors. These findings underscore that smoking cessation trajectories with e-cigarettes are complex, potentially unstable over time, and influenced by multiple factors.
Expert Commentary
The pragmatic trial by Bonevski et al. addresses a critical gap by evaluating smoking cessation interventions specifically in SUD patients post-inpatient withdrawal. The equivalence of e-cigarettes and cNRT in achieving modest cessation rates suggests both can be integrated into treatment paradigms, especially when combined with behavioural support. Safety data alleviate concerns about adverse events in this vulnerable group. However, the modest quit rates highlight persistent challenges, including high relapse propensity and complex psychosocial factors.
The systematic review analysis by Hartmann-Boyce et al. provides important context by revealing the dynamic nature of smoking abstinence over time in e-cigarette trials. The variability in risk ratios suggests that static, single-timepoint efficacy estimates may misrepresent the real-world effectiveness, especially considering relapse phenomena and ‘accidental quitting.’ These insights call for longitudinal monitoring and tailored cessation strategies that address early relapse risks, particularly in populations with SUD.
Limitations of the pragmatic trial include lack of biochemical verification of abstinence, potential variability in adherence, and generalizability limited to Australian inpatient withdrawal settings. The systematic review, while comprehensive, includes studies with variable quality and heterogeneous designs, complicating meta-analytic interpretations.
Conclusion
In patients with SUD discharged from smoke-free inpatient withdrawal services, e-cigarettes and combination nicotine replacement therapy yield comparable and modest long-term smoking abstinence rates, with favorable safety profiles. This highlights the potential for both interventions as cessation aids in this high-risk population. However, cessation success remains limited, underscoring the need for enhanced, individualized support and relapse prevention strategies. Longitudinal data reveal that smoking abstinence trajectories in e-cigarette trials are variable and risk ratios unstable, indicating that ongoing evaluation of cessation outcomes over time is essential. Future research should prioritize understanding relapse mechanisms and optimizing cessation interventions tailored to the complex needs of SUD populations.
References
Bonevski B, Rich J, Lubman DI, et al. Nicotine e-cigarettes for smoking cessation following discharge from smoke-free inpatient alcohol and other drug withdrawal services: a pragmatic two-arm, single-blinded, parallel-group, randomised controlled trial. Lancet Public Health. 2025;10(7):e568-e577. doi:10.1016/S2468-2667(25)00101-X. PMID:40602856.
Hartmann-Boyce J, Chan J, Zhitnik E, et al. Longitudinal Patterns in Smoking Abstinence in Trials of E-cigarettes for Smoking Cessation: Secondary Analysis of Data From a Systematic Review, With Meta-Analyses. Nicotine Tob Res. 2025;27(8):1486-1491. doi:10.1093/ntr/ntae313. PMID:39756408; PMCID:PMC12280167.
