Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out.

Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.
A double-blind study evaluating the long-term safety of varenicline for smoking cessation.
We assessed the safety of long-term varenicline administration for smoking cessation.
                In this randomized, double-blind, multicenter trial, eligible adult smokers (18-75 years) who smoked an average of > or =10 cigarettes/day were randomized to either varenicline 1 mg twice daily (BID) or placebo for 52 weeks. Subjects made weekly clinic visits until week 8, and then every 4 weeks until week 52, with a follow-up visit at week 53. The target quit date was the morning of the week 1 clinic visit. Brief counseling was provided at each visit, and vital signs, adverse events (AEs), and smoking status were documented. Other laboratory measures were collected at specified visits.
                A total of 251 subjects were randomized to varenicline and 126 to placebo. Approximately half of the subjects in each arm completed the study (53.8% varenicline; 46.8% placebo). Treatment-emergent AEs were observed in 96.4% of varenicline- and 82.5% of placebo-treated subjects during the study. Common varenicline-associated AEs were nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%). Most AEs were considered mild or moderate in intensity. AEs leading to discontinuation of varenicline treatment included nausea (7.6%), insomnia (3.2%), and abnormal dreams (2.4%). A single varenicline-related serious AE, bilateral subcapsular cataracts, was observed. At week 52, 7-day point prevalence abstinence rates were 36.7% (varenicline) and 7.9% (placebo).
                Varenicline 1 mg BID can be safely administered for up to 1 year. Varenicline was also a more effective smoking cessation aid than placebo throughout the study, supporting both its short- (12-week) and long-term (52-week) efficacy.