This meta-analysis of 39 randomised controlled trials, involving 5817 patients prescribed varenicline 1 mg twice daily and 4944 patients prescribed placebo, found no increased risk of suicide or attempted suicide, suicidal ideation, depression, or death in individuals treated with varenicline. Almost half of the trial participants were chronic heavy smokers (that is, they had smoked on average 20 cigarettes a day for 26 years). Five separate trials (including 1281 participants randomised to varenicline and 1143 to placebo) reported a suicide and/or suicide attempt (see appendix 3); one reported suicide only, three reported attempted suicide only, and one reported both suicide and attempted suicide. Two suicides and two attempts occurred in the varenicline group of the trials (0.08%) and two attempts occurred in the placebo group (0.05%). Use of the maximum dose of varenicline (1 mg twice daily) was associated with a 28% increased risk of fatigue, a 56% increased risk of insomnia, a 63% increased risk of sleep disorders, and more than twice the risk of abnormal dreams. There was evidence of a 25% reduction in the risk of anxiety.
