Reports of suicidality in clinical trials of montelukast

Background: In recent years, a number of drugs and drug classes have come under scrutiny by the US Food and Drug Administration regarding suicidality (including suicidal behavior and ideation). Objective: We sought to perform 2 reviews (requested by the US Food and Drug Administration) of the number of events possibly related to suicidality reported in Merck clinical trials of montelukast. Methods: Method I was a descriptive review of clinical adverse experiences (AEs) from 116 studies (double-blind and open-label, adult and pediatric, and single- and multiple-dose studies) completed as of March 2008. Summaries were constructed from investigator-reported AE terms possibly related to suicidality (completed suicide, suicide attempt, and suicidal ideation) or self-injurious behavior. Method 2 used a retrospective adjudication of investigator-reported AEs and other events listed in the study database described as possibly suicidality-related adverse events (PSRAEs) in a prespecified set of 41 double-blind, placebo-controlled trials completed as of April 2008. Results: No completed suicides were reported in any study. For the descriptive review, 20,131 adults and children received montelukast, 9,287 received placebo, and 8,346 received active control; AEs possibly related to suicidality were rare and were similar between the montelukast and placebo or active-control groups. For the adjudicated review across 22,433 patients, there were 730 adjudicated events. In 9,929 patients taking montelukast, 1 PSRAE was identified (classified as suicidal ideation); none were identified in 7,780 and 4,724 patients taking placebo and active control, respectively. Conclusions: Assessed by using 2 complementary methods, there were no reports of completed suicide, and reports of PSRAEs were rare in patients receiving montelukast and similar to those seen in control subjects. (J Allergy Clin Immunol 2009;124:691-6.)