Psychiatric adverse events associated with varenicline: an intensive postmarketing prospective cohort study in New Zealand

Drug Saf. 2011 Sep 1;34(9):763-72. doi: 10.2165/11594450-000000000-00000.


Background: Psychiatric adverse events, including depression, suicidal ideation and psychotic reactions have been reported in patients taking the smoking cessation medicine varenicline. However, data regarding the frequency of psychiatric adverse reactions in 'real-life' postmarketing use are limited to date.

Objective: The aim of the study was to calculate the occurrence rates of psychiatric adverse reactions in a nationwide general population prescribed varenicline in New Zealand.

Methods: Observational prospective cohort study using Prescription Event Monitoring methods. All New Zealand patients dispensed a prescription for varenicline from 1 April 2007 to 31 March 2008 were included in this study. Patients were followed up by multiple methods, including linkage to national morbidity and mortality datasets, questionnaires to patients' doctors and assessment of spontaneous reports sent to the Intensive Medicines Monitoring Programme. Main outcome measures were occurrence rates of psychiatric adverse events in the total patient cohort and in the subgroup for whom a follow-up questionnaire was returned (the 'responder population').

Results: The cohort for this study included 3415 patients prescribed varenicline during the first year of monitoring in New Zealand. Follow-up by record linkage was performed for 3353 (98%) patients, and questionnaires were returned for 1394 (42%) of these patients. Of 1394 questionnaires returned, 1310 were valid and defined as the 'responder' population. Sleep disorders, including insomnia, sleep disturbance, dreams and nightmares, were the most frequently reported psychiatric events and were experienced by 56 (4.3%) patients in the responder population. Symptoms of depression were reported by 39 (2.98%) patients in the responder population (24 new-onset depression, 14 worsening of pre-existing depression and 1 report of impaired motivation). Withdrawal reactions after stopping varenicline were reported by 6 (0.46%) patients in the responder population. Serious psychiatric reactions including suicide (one case), suicidal ideation (two cases) and psychotic reactions (three cases) were also identified. Six self-harm events (one fatal, five non-fatal) were identified in the total cohort, giving an occurrence rate of 0.18% (95% CI 0.06, 0.38) in this population.

Conclusions: This intensive postmarketing study of 3415 New Zealand patients demonstrates that psychiatric adverse events are commonly reported in patients taking varenicline. Approximately 3% of patients experienced symptoms of depression and the majority of these cases appeared to have a causal association with varenicline. Serious psychiatric reactions including suicide, suicidal ideation and psychotic reactions were also identified, but these were less frequently reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Benzazepines / adverse effects*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Mental Disorders / chemically induced*
  • Middle Aged
  • New Zealand
  • Nicotinic Agonists / adverse effects*
  • Product Surveillance, Postmarketing / statistics & numerical data
  • Prospective Studies
  • Quinoxalines / adverse effects*
  • Sleep Wake Disorders / chemically induced*
  • Smoking Cessation / methods*
  • Surveys and Questionnaires
  • Varenicline
  • Young Adult


  • Benzazepines
  • Nicotinic Agonists
  • Quinoxalines
  • Varenicline