Montelukast use in pediatric and adolescent patients was not associated with an increased risk of neuropsychiatric adverse events, with incidence rates nearly identical to those receiving long-acting beta-agonists, according to a recent study. 

Investigators examined the potential association between montelukast use and neuropsychiatric adverse events in pediatric and adolescent patients. Using nationwide Swedish register data from January 2007 to November 2021, they conducted a cohort study comparing 26,462 incident montelukast users with 47,829 incident long-acting beta-agonist (LABA) users aged 6 to 17 years. The study, published in JAMA Pediatrics, aimed to address ongoing concerns about montelukast’s safety, particularly following the U.S. Food and Drug Administration’s (FDA) boxed warning issued in 2020.

The primary outcome was the incidence of neuropsychiatric adverse events, including anxiety, depression, sleep-related disorders, and suicidal behaviors, as identified through diagnostic codes and prescription data. Patients with a history of neuropsychiatric events or life-limiting conditions were excluded. The researchers employed propensity score overlap weighting and inverse probability of censoring weighting to control for confounding and ensure comparability between groups. Follow-up was conducted until drug discontinuation, study end, or censoring.

Over an average follow-up of 5.8 months, 310 neuropsychiatric events occurred among the patients who received montelukast compared with 566 events among those who received LABA. The incidence rates were 2.39 and 2.41 per 100 patient-years, respectively, yielding a hazard ratio (HR) of 0.99 (95% confidence interval [CI] = 0.84–1.16), noted lead study author Viktor Wintzell, MSc, PhD, of the Division of Clinical Epidemiology in Department of Medicine Solna at the Karolinska Institutet, and his colleagues. Secondary outcomes also demonstrated no statistically significant differences between the groups: HRs for anxiety, depression, sleep-related disorders, and suicidal behaviors were 0.79 (95% CI = 0.54–1.14), 1.16 (95% CI = 0.70–1.95), 0.93 (95% CI = 0.76–1.13), and 1.31 (95% CI = 0.64–2.69), respectively. Subgroup analyses by age, sex, and asthma status revealed consistent findings.

The researchers noted no temporal differences in risks prior to and following the FDA's boxed warning issuance, and sensitivity analyses confirmed the robustness of results under varied assumptions. The study concluded that montelukast use was not associated with an increased risk of neuropsychiatric adverse events in this population. 

Full disclosures can be found in the published study.