Varenicline Failed to Help Adolescents Quit Smoking

By Lisa Rapaport

October 13, 2020

(Reuters Health) - Smokers aged 12 to 19 who sought cessation treatment didn't have any more success with varenicline than with placebo, in a recent trial.

Researchers randomly assigned 312 teens who sought smoking cessation treatment to receive 12 weeks of low-dose varenicline (0.5mg twice daily), high-dose varenicline (1mg twice daily; 0.5mg twice daily if body weight 55kg or less), or placebo.

Over weeks 9 to 12 of the intervention, continuous abstinence rates were 27% with low-dose varenicline, 20% with high-dose varenicline, and 18% with placebo. These differences - the primary endpoint for the study - weren't statistically significant.

In addition, there wasn't a statistically different 7-day point prevalence in abstinence among the three intervention groups at 12, 24, or 52 weeks, or in reduction in cigarettes smoked per day at weeks 12 or 24.

"While this study did not raise any new safety or tolerability signals for varenicline, it did not show a statistically significant advantage over placebo in smoking cessation among adolescents," said coauthor Dr. Kevin Gray, a professor of psychiatry and behavioral sciences at the Medical University of South Carolina in Charleston.

Factors maintaining cigarette smoking may differ in adolescents compared to adults, and may be heterogeneous among adolescents," Dr. Gray said by email.

"It is possible that, even if a medication precisely targets a neural mechanism underlying nicotine craving and withdrawal, psychosocial factors -- i.e., peer smoking, ambivalence about quitting -- may limit cessation success," Dr. Gray said.

Most side effects were mild, and overall treatment-emergent adverse events occurred in 53% of participants on low-dose varenicline and on placebo, and in 60% of participants on high-dose varenicline.

The most common neuropsychiatric side effects included abnormal dreams, agitation, and anxiety. Some of the non-neuropsychiatric side effects included dizziness, headache, nausea, and vomiting.

The higher than expected cessation prevalence with placebo may have obscured any potential benefit of varenicline among the study participants, the researchers note in The Lancet Child and Adolescent Health. The 12 weeks of treatment also included cessation counseling, making it hard to determine the any effect of medication independent of the other support participants received.

There's also a lot of variation in smoking patterns and smoking history among young people, and it's possible that varenicline is more effective for some subpopulations of adolescents and the study wasn't able to detect this, said Kylie Morphett of the School of Public Health at the University of Queensland in Australia.

"It's already the case that clinical guidelines in countries including the U.S.A. and Australia don't recommend varenicline as a smoking cessation treatment for adolescents, and unless future research suggests otherwise, this should remain the case," Morphett, co-author of an editorial accompanying the study, said by email. "More high quality research is needed on behavioral interventions that are effective for smoking cessation in young people."

SOURCE: and The Lancet Child and Adolescent Health, online September 24, 2020.