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

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• Picked for Family Practice (top studies of the week, 26 July 2026).
• Picked for Pulmonary and Respiratory Medicine (top studies of the week, 26 July 2026).
• Picked for Immunology and Allergy (top studies of the week, 26 July 2026).

Abstract

BACKGROUND: Montelukast is widely used in pediatric asthma treatment, and concerns have been raised regarding its risk of neuropsychiatric adverse events (NEs). Existing studies predominantly focus on its monotherapy use, neglecting the clinically common scenario of combination therapy with inhaled corticosteroids (ICS). This study aims to systematically evaluate whether montelukast combined with ICS increases the risk of neuropsychiatric adverse events in pediatric and adolescent asthma patients compared to ICS monotherapy, thereby providing safety evidence for clinical practice. METHOD: This study conducted a systematic review and meta-analysis according to the PRISMA guidelines, with registration number [CRD420251070948]. Five major databases-PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials-were searched to identify studies comparing montelukast plus ICS with ICS alone. The primary outcome measure was the occurrence of neuropsychiatric adverse events. RESULTS: A total of 6 studies (3 RCTs, 3 cohort studies) involving 559 pediatric patients were included. Pooled analysis showed that the incidence of neuropsychiatric adverse events in the combination therapy group was 12.1%, higher than the 8.6% in the control group. The pooled risk ratio (RR) 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 translates to approximately 35 additional neuropsychiatric events per 1,000 children (95% CI: -12 to +82). The number needed to harm (NNH) was 29, indicating that 29 patients would need to receive combination therapy to cause one additional adverse event. Although not statistically significant, this suggests a potential upward trend in risk warranting clinical attention. Subgroup analyses revealed headaches and sleep disturbances as the most common events, with respective risk increases of 62% and 53%, though these differences also failed to reach statistical significance. Sensitivity analyses and bias assessments demonstrated robust results. CONCLUSIONS: A comprehensive analysis indicates that the combination of montelukast with ICS may increase the risk of neuropsychiatric adverse events in paediatric asthma patients, with an absolute effect of approximately 35 additional cases per 1,000 individuals. However, this finding exhibits considerable statistical uncertainty, and the predicted interval suggests potential inconsistencies in future research outcomes. Although not statistically significant, based on underlying mechanisms and public health implications, it is recommended that clinicians exercise caution when assessing treatment risks in high-risk populations. Furthermore, prospective validation studies are encouraged.

Abstract as published, via PubMed.