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 randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers.
Rates of smoking in East Asian men range from >35% to >60%, and are increasing in women and the young.
                This study evaluated the efficacy and tolerability of 1 mg BID varenicline, a novel alpha4beta2 nicotinic acetylcholine receptor partial agonist, for smoking cessation in smokers in Taiwan and Korea.
                A randomized, double-blind, placebo-controlled, 12-week treatment, 12-week follow-up trial was conducted at 5 sites each in Korea and Taiwan. Eligible subjects, smoking >or=10 cigarettes/d, received brief smoking-cessation counseling and were randomly assigned in a 1:1 ratio to varenicline 1 mg BID (titrated during the first week) or placebo. Smoking status was established by self-report and confirmed at clinic visits by end-expiratory carbon monoxide <or=10 ppm. The primary end point was continuous abstinence rate (CAR) during the last 4 weeks of treatment. Secondary end points included CAR from weeks 9 to 24 and 7-day point prevalence (PP) of abstinence at weeks 12 and 24. Craving, withdrawal, and smoking satisfaction were determined by the Minnesota Nicotine Withdrawal Scale, the Brief Questionnaire of Smoking Urges, and the modified Cigarette Evaluation Questionnaire. Observed or volunteered adverse-event data were recorded at clinic visits.
                Overall, 126 subjects (84.9% male) received varenicline, and 124 (92.7% male) received placebo, Subjects were aged 21 to 73 years (mean age, 39.7 and 40.9 years for varenicline and placebo groups, respectively), and the mean (range) body weights were 69.0 (44.8-110.0) kg and 71.4 (45.5-102.0) kg, respectively. Subjects had smoked for 3 to 52 years (mean, 20.2 and 22.1 years in the varenicline and placebo groups, respectively). Subjects had smoked a mean of 23 cigarettes/d over the past month, with 51.6% (varenicline) and 46.0% (placebo) having made 1 or more prior serious quit attempts. Smoking-cessation rates at the end of treatment were 59.5% with varenicline versus 32.3% with placebo (P < 0.001). CARs through 12 weeks post-treatment (weeks 9-24) were 46.8% with varenicline and 21.8% with placebo (P < 0.001). The 7-day PP was 67.5% with varenicline versus 36.3% with placebo at week 12, and 57.1% versus 29.0% with placebo at week 24 (both, P < 0.001). Treatment-emergent, all-causality adverse events with an incidence >or= 5% for varenicline were nausea (43.7% for varenicline vs 11.3% placebo), insomnia (15.1% vs 13.7%), increased appetite (7.9% vs 6.5%), constipation (7.1% vs 2.4%), anxiety (5.6% vs 2.4%), and abnormal dreams (5.6% vs 0.8%). Adverse events resulted in <10% treatment discontinuations overall.
                Varenicline was an efficacious and well-tolerated pharmacotherapy for smoking cessation in this group of Asian smokers over a 12-week treatment period, and its effects persisted for a further 12-week follow-up period.