Lamoure J., Stovel J. Varenicline and Suicidal Ideations. How Common is It?. Cdn J of CME 2012; 24(2): 14 more

Varenicline and Suicidal Ideation: How Common Is It? 3. Varenicline and suicidal ideation: How common is it and should patients be warned about the side effects? Question submitted by: Dr. Tom Echlin Windsor, Ontario In Canada, varenicline is currently indicated for smoking cessation in conjunction with counselling.1 There have been numerous reports of increased suicidal ideation in patients taking varenicline, and in patients that are quitting smoking. This has resulted in the Health Canada Advisory warning healthcare providers about the increased risk of serious neuropsychiatric adverse events in those patients taking varenicline. Specifically, depressed mood, agitation, hostility, changes in behaviour, suicidal ideation and suicide, as well as worsening of pre-existing psychiatric illness have been observed.2 This scenario is very reminiscent for me of the mid 1980’s when fluoxetine was first launched in the USA. Health Canada reports that between April 2007 and April 30, 2008, a total of 226 Canadian cases of all cause neuropsychiatric adverse events were reported out of a total of 708,534 prescriptions filled.2 At least seven of these Canadian cases reported between April and November of 2007 involved suicidal ideation.3 Unfortunately, there is no clear Canadian data on how common suicidal ideation specifically is, since such rates are reliant upon voluntary reporting.2 However, there have been studies in the literature that have examined the frequency of suicidal ideation in patients taking varenicline. An analysis of pooled data from ten smoking cessation trials completed by December 2008 found that there were no incidences of suicidal ideation or suicide attempts in the varenicline group compared to two events (0.1%) observed in the placebo group.1 Additionally, a study from the United Kingdom found no increase in suicidal ideation in a cohort of > 80,000 smokers taking varenicline compared with those using other smoking cessation products.4, 5 When evaluating the cases of increased risk of suicidal ideation associated with varenicline, it is important to take into consideration a variety of potentially confounding factors that may have contributed to such reports. Varenicline has some inherent antidepressant properties, which may be linked to neuropsychiatric effects, but we would not hesitate to judiciously use an antidepressant in a suicidal depressed patient over the age of 25. We need to ask who is more likely to smoke, as these patients are more prone to neuropsychiatric symptoms, given that smoking offers a form of self-medication, albeit harmful. Effects of partial or complete nicotine withdrawal while taking varenicline may inherently be associated with some of the neuropsychiatric symptoms reported. I also believe there is a grief reaction associated with smoking cessation and other potential contributing factors for suicidality, which include concurrent or past psychiatric conditions, as well as the concomitant use of other CNS acting medications and/or alcohol or substance use/misuse.2 However, there have been reported cases where such confounding factors did not appear to be present (e.g., cases where suicidal ideation occurred within the first week of therapy and prior to smoking cessation). Therefore, it is essential that all patients be educated about the need to monitor for the development of suicidal ideation. Patients should be counseled to stop taking varenicline and contact their physician immediately if they do develop suicidal ideation or behaviour while on varenicline. If the patient has a history of psychiatric conditions or symptoms (even if stable and well-controlled), they should be carefully monitored throughout varenicline therapy. If suicidal ideation or any other neuropsychiatric symptom is experienced while on varenicline, it is prudent to report such adverse events to Health Canada and the manufacturer for further assessment and evaluation.2 References 1. Canadian Pharmacists Association. eCompendium of Pharmaceutical Specialties: Champix Monogrpah. January 2012. https://www-e-therapeuticsca.myaccess.library.utoronto.ca/home. whatsnew.action. Accessed on January 5, 2012. 2. Health Canada. Health Canada Endorsed Important Safety Information on CHAMPIX (varenicline tartrate). June 13, 2008. http://www.hc-sc.gc.ca/dhpmps/medeff/advisoriesavis/prof/_2008/champix_hpc-cpseng.php. Accessed January 5, 2012. 3. Longo M, Kalajdzic T, McMorran M: Varenicline (Champix) and Serious Psychiatric Reactions. Health Canada Canadian Adverse Reaction Newsletter. 2008; 18(2):1–2. 4. Mineur YS, Picciotto MR: Nicotine Receptors and Depression: Revisiting and Revising the Cholinergic Hypothesis. Trends Pharmacol Sci. 2010; 12:580–586. 5. Gunnell D, Irvin D, Wise L, et al: Varenicline and Suicidal Behaviour: a Cohort Study Based on Data from the General Practice Research Database. Brit. Med J 2009; 339, b3805. Answered by: Dr. Joel Lamoure Professor Jessica Stovel 14 The Canadian Journal of CME / February 2012