Singulair (montelukast) is a leukotriene receptor antagonist used for control of asthma and allergies. In March 2008, the FDA started a review to investigate numerous postmarket reports of suicidality related to the use of Singulair. Results of those reviews were recently published in the October 2009 issue of the Journal of Allergy & Clinical Immunology.
Each review went back through research data acquired during drug development to look for patterns that may have represented suicidality or "possible suicidality-related adverse events (PSRAEs)." These reviews were ordered by the FDA and completed by employees of the drug's manufacturer Merck.
There were no suicides reported during the clinical trials for Singulair. There was one case of suicidal ideation in almost 10,000 patients taking montelukast and none in over 11,000 control subjects (placebo and active control). The conclusion drawn was that PSRAEs were rare and similar to the control groups.
A related article in the same issue looked at behavioral-related adverse events (BRAEs) during Singulair clinical trials. The frequency of patients with 1 or more BRAEs was 2.73% and 2.27% in the montelukast and placebo groups, respectively. The frequency with a severe BRAE was 0.03% in both montelukast and placebo groups, suggesting no difference. And the frequency of patients being taken off of montelukast because of a BRAE was 0.07% while 0.11% of placebo patients were discontinued from the study for a BRAE.
Potential limitations of these reviews include the fact that they were completed by employees of Merck, and that they only included data collected during drug development, where suicidality would lead to exclusion from the study.
The latter issue is important because severe asthma and allergies have been associated with depression and anxiety and thus, such patients may be more prone to suicidality. Using Singulair in such patients requires proper counseling and close follow-up.
Anecdotally, I have seen patients (especially children) who do experience mood changes on Singulair. We stop the medication and provide other controllers of their symptoms, and there has never been complicating issues. For what it’s worth, I have also seen similar behavioral changes on antihistamines and even certain inhaled corticosteroids. And we commonly screen for depression/anxiety in our patients.
Practioners and patients should discuss the risks of behavioral changes with the use of Singulair before prescribing this medication.
