Cytisine and varenicline are partial receptor agonists that inhibit the attachment of nicotine to receptors. Both are effective aids to smoking cessation. Varenicline is commonly used for this purpose in the United States and worldwide.
Cytisine has been available for smoking cessation for more than 40 years, largely in Eastern Europe, and is not available in the United States. Cytisine is less expensive than varenicline and other nicotine replacement therapy (NRT). Placebo-controlled trials and several systematic reviews indicate that cytisine almost doubles the chances of quitting smoking at 6 months. No trials have compared the effectiveness of cytisine for smoking cessation with NRT.
This open-label noninferiority trial was designed to determine whether cytisine was as effective as NRT in helping smokers to quit. The study was conducted in New Zealand from 2011 to 2013. Eligible participants were male and female adult daily smokers, who were motivated to quit and had called the national quitline. Cytisine was provided free of charge by mail, and NRT was provided through vouchers for nicotine patches, gums, or lozenges. All participants received low-intensity, telephone-delivered behavioral support through the quitline. The primary study outcome was self-reported continuous abstinence at 1 month. Adverse events were assessed with patient self-reports.
A total of 1310 adult daily smokers were randomly assigned in a 1:1 ratio to receive cytisine for 25 days or NRT for 8 weeks. The 1-month continuous abstinence rates were significantly higher in the cytisine group than those in the NRT group (40% [264/655] vs 31% [203/655]); the risk difference was 9.3 percentage points with a 95% confidence interval of 4.2 to 14.5. Cytisine was more effective than NRT for continuous abstinence at 1 week, 2 months, and 6 months. Prespecified subgroup analysis according to sex showed that the 1-month continuous abstinence rate with cytisine was superior to NRT among women and not significantly different among men. Adverse events over 6 months were reported more frequently in the cytisine group (288 events among 204 participants) than in the NRT group (174 events among 134 participants) (P < 0.001). The most common problems in the cytisine group were nausea and vomiting and sleep disorders.
These findings show that cytisine combined with behavioral support is superior to NRT in helping smokers quit smoking but is associated with a higher frequency of adverse events. Long-term studies of larger size are needed to fully evaluate adverse events with cytosine.