Risk of neuropsychiatric adverse events with montelukast combined with inhaled corticosteroids (ICS) in the treatment of asthma in children and adolescents: a systematic review and meta-analysis.

OBJECTIVE

To evaluate whether montelukast combined with inhaled corticosteroids (ICS) increases the risk of neuropsychiatric adverse events (NEs) compared with ICS monotherapy in pediatric and adolescent asthma patients.

METHODS

A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration: CRD420251070948). PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov were searched for studies comparing montelukast plus ICS with ICS alone. The primary outcome was the occurrence of NEs.

RESULTS

Six studies (three randomized controlled trials and three cohort studies) involving 559 pediatric patients were included. The incidence of NEs was 12.1% in the montelukast plus ICS group and 8.6% in the ICS-only group. The pooled risk ratio was 1.41 (95% CI: 0.89-2.22; p = 0.14), with an absolute risk difference of 3.5% (95% CI: -1.2% to 8.2%). This corresponded to approximately 35 additional events per 1000 children (95% CI: -12 to 82). Sensitivity analyses and risk-of-bias assessments supported the robustness of the findings. Subgroup analyses suggested possible increases in headache and sleep disturbances, although these differences were not statistically significant.

CONCLUSIONS

Montelukast combined with ICS may be associated with an increased risk of NEs in pediatric asthma patients; however, the current evidence remains uncertain. Clinicians should consider potential neuropsychiatric risks when prescribing combination therapy, particularly for susceptible children. Further prospective studies are warranted to confirm these findings.