Reference: JAMA. 2025 Apr 23:e253810
Practice Point: Varenicline seems to help adolescents and young adults kick the nicotine vaping habit.
EBM Pearl: Uneven adherence rates, for whatever reason, impact study validity.
It started as a cloud-chasing trend that quickly became a public health haze. Vaping and e-cigarettes were initially marketed as a “healthier” alternative to smoking cigarettes. Perhaps, but for many young people it’s an addiction disguised in fruity flavors and flashy devices. A recent clinical trial published in JAMA offers compelling evidence that varenicline—a medication already FDA approved for smoking cessation—could be an effective tool to help adolescents and young adults quit vaping.
Conducted by researchers at Massachusetts General Hospital, the study focused on 261 participants between ages 16 and 25 years who vaped nicotine daily but had little-to-no history of cigarette use. Participants were randomly assigned to 1 of 3 study arms: (1) varenicline with behavioral counseling and text messaging support, (2) placebo with behavioral counseling and text messaging support, or (3) text messaging support only. The primary outcome was biochemically verified continuous vaping abstinence during weeks 9-12 of varenicline treatment.
Varenicline was associated with a significant increase in continuous abstinence rates compared to placebo (51% vs. 14% during weeks 9-12, adjusted odds ratio [OR] 6.5, 95% CI 3-14.1) or text messaging support (51% vs. 6%, adjusted OR 16.9, 95% CI 6.2-46.3). The secondary outcome of continuous abstinence from weeks 9-24 also favored varenicline over placebo (28% vs. 7%, adjusted OR 6, 95% CI 2.1-16.9) and text messaging support (28% vs. 4%, adjusted OR 11, 95% CI 3.1-38.8). Varenicline was generally well-tolerated, with no serious side effects reported. Only 3 participants dropped out due to adverse events, and importantly, there was no evidence that those who quit vaping switched to combustible tobacco use.
One limitation of this study is the difference in adherence rates. Those taking varenicline had 72.8% medication adherence while those taking placebo had 63.5% adherence. For counseling, 78.4% of the varenicline group vs. 59.8% of the placebo group attended ≥ 80% of counseling sessions. Even text messaging had this unusual adherence gap, with 41% enrolling in the varenicline group, 36% in the placebo group, and 74% in the texting support group.
In clinical trials, consistent adherence rates across study arms are important in helping ensure that differences in outcomes are due to the intervention itself, not some known or unknown confounder. There were other factors that cloud the validity of the results, such as the lack of believable blinding due to non-severe side effects of varenicline, baseline differences in cannabis use and different financial incentives between groups, and the fact that volunteer enrollment was solicited. While we don’t necessarily doubt that varenicline can be effective for vaping cessation, we are less convinced that the magnitude of effect is as great as they say it is. But maybe it is; the risk ratio for varenicline to placebo for cigarette cessation is on the order of 2-3 as well. We’ll just need at least one more higher quality study that can replicate these results. Despite the limitations, these findings suggest that varenicline may be a go-to instrument in your toolkit for young people who vape and might consider quitting. With an established safety profile and FDA approval already in place for smoking cessation, this medication is showing off-label promise in helping people who want to quit vaping trade their pods for progress. Varenicline is not a magic pill, but when paired with counseling and text message support, it might help your patients clear the haze of vaping for good.
For more information, see the topic Treatment for Tobacco Use in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Rich Lamkin, MPH, MPAS, PA-C, Clinical Writer at DynaMed.
Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Dan Randall, MD, MPH, FACP, Senior Deputy Editor at DynaMed; Gayle Sulik, PhD, Senior Medical Editor and Team Lead for Palliative Care at DynaMed; McKenzie Ferguson, PharmD, BCPS, Senior Clinical Writer at DynaMed; Matthew Lavoie, Senior Medical Copyeditor, BA, at DynaMed; Hannah Ekeh, MA, Senior Associate Editor II at DynaMed; and Jennifer Wallace, BA, Senior Associate Editor at DynaMed.