Is Cytisinicline Effective for Smoking Cessation?

The medication cytisinicline (also known as “cytisine”) binds α4β2 nicotinic acetylcholine receptors to block the reinforcing effects of nicotine and reduce withdrawal symptoms. This double-blind, randomized, phase 3 clinical trial compared cytisinicline with placebo for smoking cessation. Adults with smoking who were ready to quit (N=810) were randomized to 1 of 3 groups: 6 weeks cytisinicline, 12 weeks cytisinicline, or placebo (people in the intervention groups received 3mg cytisinicline 3 times daily). All participants also received weekly behavioral counseling for 12 weeks. Outcomes were continuous smoking abstinence during the last 4 weeks of treatment and through 24 weeks of follow-up. Craving and tolerability were also assessed.

• Continuous abstinence was greater among patients receiving the 6-week course compared with those in the placebo group at the end of treatment (25 versus 4 percent, respectively) and at 24 weeks (9 versus 3 percent).
• Continuous abstinence was greater among patients receiving the 12-week course compared with placebo at the end of treatment (33 versus 7 percent, respectively) and at 24 weeks (21 versus 5 percent).
• Craving declined more rapidly among patients in the treatment groups than among those receiving placebo.
• Abnormal dreams and insomnia were more common in the cytisinicline groups (~10 percent), but there were no serious adverse events attributable to receipt of the medication.

Comments: Cytisinicline is a plant-based alkaloid that is similar to varenicline and commercially available in Europe. This trial provides strong evidence of efficacy at higher doses and longer treatment duration than what is recommended by the manufacturer (i.e., 1.5mg 6 times daily with tapering over 25 days). These dosing regimens have not been compared head-to-head with varenicline, but cytisinicline could provide an advantage in terms of medication costs and tolerability. One limitation of the study is that people with comorbid serious mental illness or substance use disorders—groups disproportionately harmed by tobacco—were excluded from the trial.

Aaron D. Fox, MD

Reference: Rigotti NA, Benowitz NL, Prochaska J, et al. Cytisinicline for smoking cessation: a randomized clinical trial. JAMA. 2023;330(2):152–160.