The Impact of Montelukast's Black Box Warning on Pediatric Mental Health Adverse Event Reports

In March 2020, the US Food and Drug Administration (FDA) required a black box warning for montelukast due to serious mental health side effects. We hypothesized the warning would lead to an overall decrease in reports of mental health symptoms and disorders related to montelukast in both -pre-adolescent and adolescent groups.

Adverse events of pre-adolescent and adolescent children taking montelukast sodium were reviewed from March 1, 2018 to March 3, 2020 and March 4, 2020 to February 28, 2022 using the FDA's Adverse Events Reporting System. The objective was to determine if mental health adverse event reports were influenced by placement of a Boxed Warning. Adverse reactions were grouped into 8 categories deemed to be related to mental health guided by the research team's interpretation of the FDA Sentinel Report. Chi-square tests were used to compare time periods and reports of the mental health categories.

Of the 1570 reports assessed, 1295 (82.5%) included ≥1 mental health concern. Nine hundred ninety-six (84.2%) of the 1183 reports involving pre-adolescents and 299 (77.3%) of the 387 reports involving adolescents included ≥1 mental health reaction. Statistically significant changes for pre-adolescents were found in reports related to depression (χ² (1) = 4.30, p = 0.044), and sleep (χ² (1) = 5.74, p = 0.019), which both decreased between the pre and post periods. The only statistically significant change across categories for adolescents was a reduction in aggression reports between time periods (χ² (1) = 8.5, p = 0.004).

After placement of an FDA black box warning on montelukast, total number of reports -including mental health adverse events decreased in pre-adolescents; however, several categories -assessed increased for adolescents.