Drug Safety

, Volume 34, Issue 9, pp 763–772 | Cite as

Psychiatric Adverse Events Associated with Varenicline

An Intensive Postmarketing Prospective Cohort Study in New Zealand
Original Research Article


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.


  1. 1.
    Tonstad S, Davies S, Flammer M, et al. Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. Drug Saf 2010 Apr 1; 33(4): 289–301PubMedCrossRefGoogle Scholar
  2. 2.
    Harrison-Woolrych M. Psychiatric reactions with varenicline: interim results from intensive monitoring in New Zealand. Prescriber update. Medsafe 2009: 9 [online]. Available from URL: http://www.medsafe.govt.nz/profs/PUArticles/Varenicline%20Interim%20Results-May09.htm [Accessed 2011 Jul 12]
  3. 3.
    Elijah J. Varenicline (Champix): an update. Aust Prescrib 2010 Aug; 33(4): 120Google Scholar
  4. 4.
    Pfizer Ltd. New Zealand data sheet for Champix. Auckland: Pfizer, 2011Google Scholar
  5. 5.
    Gunnell D, Irvine D, Wise L, et al. Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database. BMJ 2009; 339: b3805PubMedCrossRefGoogle Scholar
  6. 6.
    Moore TJ, Furberg CD. Varenicline and suicide: risk of psychiatric side effects with varenicline [letter]. BMJ 2009; 339: b4964PubMedCrossRefGoogle Scholar
  7. 7.
    Kasliwal R, Wilton LV, Shakir SA. Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. Drug Saf 2009; 32(6): 499–507PubMedCrossRefGoogle Scholar
  8. 8.
    Kunac DL, Harrison-Woolrych M, Tatley MV. Pharmacovigilance in New Zealand: the role of the New Zealand Pharmacovigilance Centre in facilitating safer medicines use. N Z Med J 2008 Oct 3; 121(1283): 76–89PubMedGoogle Scholar
  9. 9.
    Harrison-Woolrych M, Coulter DM. PEM in New Zealand. In: Mann R, Andrews EB, editors. Pharmacovigilance. 2nd ed. Chichester: John Wiley and Sons Ltd, 2006: 313–28Google Scholar
  10. 10.
    Harrison-Woolrych M, Ashton J. Utilization of the smoking cessation medicine varenicline: an intensive post-marketing study in New Zealand. Pharmacoepidemiol Drug Saf 2010 Sep; 19(9): 949–53PubMedCrossRefGoogle Scholar
  11. 11.
    Karch FE, Lasagna L. Adverse drug reactions: a critical review. JAMA 1975 Dec 22; 234(12): 1236–41PubMedCrossRefGoogle Scholar
  12. 12.
    Edwards IR, Biriell C. Harmonisation in pharmacovigilance. Drug Saf 1994 Feb; 10(2): 93–102PubMedCrossRefGoogle Scholar
  13. 13.
    Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006 Jul 5; 296(1): 47–55PubMedCrossRefGoogle Scholar
  14. 14.
    Rigotti NA, Pipe AL, Benowitz NL, et al. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation 2010 Jan 19; 121(2): 221–9PubMedCrossRefGoogle Scholar
  15. 15.
    Harrison-Woolrych M, Herbison P, McLean R, et al. Incidence of thrombotic cardiovascular events in patients taking celecoxib compared with those taking rofecoxib: interim results from the New Zealand Intensive Medicines Monitoring Programme. Drug Saf 2005; 28(5): 435–42PubMedCrossRefGoogle Scholar
  16. 16.
    FDA. Varenicline and bupropion: reports of suicidality associated with use of varenicline and bupropion. FDA Drug Saf Newsletter 2009; 2(1): 1–4Google Scholar
  17. 17.
    Moore TJ, Glenmullen J, Furberg CD. Thoughts and acts of aggression/violence toward others reported in association with varenicline. Ann Pharmacother 2010 Sep; 44(9): 1389–94PubMedCrossRefGoogle Scholar
  18. 18.
    Harrison-Woolrych M. Varenicline and suicide: safety data from New Zealand [letter]. BMJ 2009; 339: b5654PubMedCrossRefGoogle Scholar
  19. 19.
    Fischer MA, Stedman MR, Lii J, et al. Primary medication non-adherence: analysis of 195,930 electronic prescriptions. J Gen Intern Med 2010 Apr; 25(4): 284–90PubMedCrossRefGoogle Scholar
  20. 20.
    Laine P, Marttila J, Lindeman S. Hallucinations in the context of varenicline withdrawal. Am J Psychiatry 2009 May; 166(5): 619–20PubMedCrossRefGoogle Scholar
  21. 21.
    May AC, Rose D. Varenicline withdrawal-induced delirium with psychosis. Am J Psychiatry 2010 Jun; 167(6): 720–1PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Intensive Medicines Monitoring Programme, Department of Preventive and Social MedicineUniversity of OtagoDunedinNew Zealand

Personalised recommendations