Mental health related adverse events of cytisine and varenicline in smokers with and without mental health disorders: Secondary analysis of a randomized controlled trial

Introduction: Little is known about the adverse events (AEs) of cytisine versus varenicline among individuals with mental health disorders (MHDs), highlighting the necessity for further exploration to inform clinical practice. This secondary analysis of clinical trial data aimed to investigate the effect of varenicline vs. cytisine regarding mental-health-related AEs (MH-related AEs) on smokers with and without MHDs. Methods: Australian daily smokers interested in quitting were randomised to varenicline (84 days) or cytisine (25 days) and categorised by self-reported MHD diagnosis or treatment in the past year (MHD or non-MHD groups). Treatment adherence was assessed by self-reported number of doses taken during the active treatment phase via two check-in calls (at one month), while AEs were evaluated through four phone interviews: two check-in calls (one month) and follow-up calls at four and seven months. Logistic regression analysis compared MH-related AEs between groups, including only participants taking at least one dose. Results: Of 1452 smokers 246 reported MHDs, 725 received cytisine and 727 received varenicline. Median number of doses taken was comparable between MHD (34 cytisine and 12 varenicline) and non-MHD (33 cytisine and 13 varenicline) groups. MH-related AEs were: 14.1 % (n = 30) in MHD (12.5 % in cytisine and 15.4 % in varenicline), and 11.8 % (n = 126) in non-MHD group (10.9 % in cytisine and 13.7 % in varenicline). No significant difference in MH-related AE occurrence was identified between medication groups (aOR=0.96, =0.96, 95 % CI 0.4 to 2.2, p-value = 0.94). Conclusion: Comparable MH-related AEs were observed between smokers with and without MHDs, suggesting that cytisine, like varenicline, may be well-tolerated by those with MHDs. However, larger clinical trials focused on MH-related AEs are needed for more conclusive evidence.