Peer-reviewed article

Neuropsychiatric outcomes after montelukast versus inhaled corticosteroids in pediatric asthma: a pooled birth cohort study.

Jiao XF, Ducharme FM, Leal LF, Longo C, Sheehy O et al. · 1 Oct 2026

Abstract

Background The evidence regarding montelukast‑associated neuropsychiatric adverse events in children with asthma is controversial and inconclusive. We sought to further examine the association between use of montelukast and the risk of neuropsychiatric events in children with asthma. Methods We conducted a pooled analysis of two birth cohorts: the AMerican PREGNANcy-Mother-Child CohorT (AM-PREGNANT) from the US, and the Quebec Pregnancy Cohort (QPC) from Canada. We included children aged 1 to < 18 years with the first incident diagnosis of asthma after birth and whose initial asthma controller therapy was either montelukast monotherapy or inhaled corticosteroids (ICS) monotherapy. The primary outcomes were sleep disorders and attention-deficit/hyperactivity disorder (ADHD), while secondary outcomes included mood disorders, anxiety disorders, and oppositional defiant and conduct disorders. We used Cox proportional hazards regressions, adjusting for potential confounders, to quantify the associations in each birth cohort independently. A random effects Meta-analysis was used to pool outcome-specific results if heterogeneity was acceptable. Results In AM-PREGNANT, 85,322 asthmatic children were included, with 21,534 in the montelukast monotherapy group and 63,788 in the ICS monotherapy group. In QPC, 11,854 asthmatic children were included, with 373 in the montelukast monotherapy group and 11,481 in the ICS monotherapy group. Use of montelukast was significantly associated with increased risks of ADHD (pooled adjusted hazard ration [HR], 1.40; 95% confidence interval [CI], 1.19-1.66) and oppositional defiant and conduct disorders (adjusted HR, 1.43; 95% CI, 1.13-1.82) compared to ICS; however, AM-PREGNANT and QPC yielded inconsistent findings regarding sleep disorders. In the subgroup analyses, use of montelukast was significantly associated with an increased risk of sleep disorders in the controlled and partly controlled asthma subgroup and in children who had not used oral corticosteroids during follow-up time when compared to ICS. There were no significant between-group differences with regards to mood disorders or anxiety disorders. Conclusions Among children newly diagnosed with asthma, use of montelukast is associated with increased risks of ADHD and oppositional defiant and conduct disorders compared to ICS; among those with newly diagnosed controlled, partly controlled, or non-severe asthma, use of montelukast is associated with an increased risk of sleep disorders compared to ICS.