In a significant advancement for youth nicotine addiction treatment, researchers have demonstrated that varenicline substantially improves vaping cessation rates among adolescents and young adults when combined with behavioral support. The findings, published in JAMA, represent the first rigorous evaluation of pharmacotherapy for nicotine vaping cessation specifically in youth populations.
The three-arm randomized clinical trial enrolled 261 participants aged 16 to 25 years who reported daily or near-daily nicotine vaping and expressed a desire to reduce or quit. Conducted between June 2022 and May 2024, the study compared 12 weeks of varenicline to placebo, with both groups receiving brief remote counseling, against an enhanced usual care group that received only a referral to a text-based cessation program.
Varenicline Significantly Outperforms Placebo and Usual Care
The results were striking. During the final four weeks of treatment (weeks 9-12), participants receiving varenicline achieved a 51% continuous abstinence rate compared to just 14% in the placebo group. This significant advantage persisted through the follow-up period, with 28% of the varenicline group maintaining abstinence from weeks 9 through 24, versus only 7% in the placebo group.
When compared to enhanced usual care, the differences were even more pronounced. The enhanced usual care group showed only a 6% abstinence rate during weeks 9-12 and 4% during weeks 9-24, demonstrating the substantial benefit of varenicline treatment (adjusted odds ratio = 16.9; 95% CI, 6.2-46.3 for weeks 9-12).
"To our knowledge, this is the first pharmacotherapy trial for nicotine vaping cessation in youth," the study authors noted. "These findings inform clinicians that they need to use medication in the form of varenicline to help their young patients to quit vaping nicotine when those patients are addicted to nicotine," explained Dr. A. Eden Evins, director of the Massachusetts General Hospital Center for Addiction Medicine and Cox Family Professor of Psychiatry at Harvard Medical School.
Addressing a Growing Public Health Concern
The study addresses a critical public health issue, as e-cigarettes have become the most widely used nicotine product among youth. According to recent data, 7.8% of high school students in 2024 and 24.1% of adults between 18 and 25 years of age in 2023 reported recent e-cigarette use. Despite this prevalence, few evidence-based treatments have been available for this age group.
The researchers emphasized the importance of early intervention, noting that "earlier age of drug initiation is associated with more rapid transition to substance use disorder and that adolescent nicotine exposure specifically increases subsequent tobacco smoking and other substance use disorders."
Safety Profile and Adherence
Varenicline was generally well-tolerated among the young participants. Treatment-emergent adverse events were reported in 86% of the varenicline group, compared to 79% in both the placebo and enhanced usual care groups. The most common side effects included nausea (58% vs. 27% in placebo), vivid dreams (39% vs. 16%), and insomnia (31% vs. 19%).
Most adverse events were mild to moderate in severity, with few severe events reported. Only two participants in the varenicline group and one in the placebo group discontinued treatment due to adverse events.
Interestingly, researchers observed stronger medication adherence in the varenicline group compared to placebo, with participants taking more pills (120.2 vs. 104.8 out of 165) and attending more counseling sessions (78.4% vs. 59.8% attended at least 80% of sessions).
Study Limitations and Future Directions
The authors acknowledged several limitations of their research. While retention was high across all groups (97.3% of participants completed the 24-week study), intervention uptake was lower in the placebo group, potentially due to differences in early treatment effects. The study was also underpowered for some comparisons and may not generalize to individuals who regularly use both combustible tobacco and e-cigarettes.
Dr. Evins noted that future studies might employ different approaches to ensure medication adherence: "Future studies in adolescents will likely use incentivized video recording of medication adherence to improve study-related treatment adherence and retention in the study."
Clinical Implications
This landmark study provides clinicians with valuable evidence for treating nicotine vaping addiction in young people. The findings suggest that pharmacotherapy, specifically varenicline, should be considered alongside behavioral interventions for youth seeking to quit vaping.
"Varenicline, when added to brief, remotely delivered behavioral counseling, is well-tolerated and promotes vaping cessation compared with placebo in youth with moderate to severe addiction to vaped nicotine," the authors concluded.
As vaping continues to be a significant health concern among adolescents and young adults, these results offer hope for more effective treatment approaches tailored to this vulnerable population.
