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Montelukast combined with inhaled corticosteroids may increase the risk of neuropsychiatric adverse events in pediatric asthma patients compared to ICS monotherapy

A systematic review and meta-analysis of 6 studies (3 RCTs, 3 cohort studies) involving 559 pediatric patients found that the combination of montelukast with ICS was associated with a 12.1% incidence of neuropsychiatric adverse events versus 8.6% with ICS alone. The pooled risk ratio was 1.41 (95% CI: 0.89-2.22, P=0.14), with an absolute risk difference of 3.5%, translating to approximately 35 additional events per 1,000 children, though this result was not statistically significant.

Last updated: Jul 28, 2026•0 RCTs•1 Meta-analyses•📖 Read as article →

Evidence Score

Evidence Score49/100
Human RCT☆☆☆☆☆
Meta-analysis★★★☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. 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.

observational

Yang Q, Guo C, Yu X, Liu X, Xie J, Liu K · The Journal of asthma : official journal of the Association for the Care of Asthma (2026)

Participants: N/A
Duration: Not specified in abstract
Intervention: Montelukast combined with inhaled corticosteroids (ICS)
Outcome: Occurrence of neuropsychiatric adverse events (including headaches and sleep disturbances)
Effect Size: RR=1.41, absolute risk difference 3.5% (95% CI: -1.2% to +8.2%)
Population: Children and adolescents with asthma (pediatric patients, age not further specified in abstract)

Result:

PubMed: 42501004DOI: 10.1080/02770903.2026.2706354

Mechanism Graph

Montelukast is a leukotriene receptor antagonist that modulates inflammatory pathways in asthma
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Combination with ICS may alter drug metabolism or central nervous system exposure
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Potential neuropsychiatric effects may involve leukotriene receptor activity in the brain
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Result: Increased risk of neuropsychiatric adverse events (not statistically significant)

Limitations

  • ⚠The finding was not statistically significant (P=0.14), indicating considerable statistical uncertainty
  • ⚠Only 6 studies were included with a total sample size of 559 patients, limiting power to detect small effects
  • ⚠The abstract does not specify the age range, duration of treatment, or control for confounding variables in cohort studies

Frequently Asked Questions

Does montelukast combined with ICS significantly increase neuropsychiatric adverse events in children?▼

The meta-analysis found a 41% relative risk increase (RR=1.41) but this was not statistically significant (P=0.14), so the evidence is inconclusive and suggests a potential trend rather than a confirmed risk.

What are the most common neuropsychiatric adverse events reported?▼

Subgroup analyses identified headaches and sleep disturbances as the most common events, with risk increases of 62% and 53% respectively, though these also did not reach statistical significance.

How many children would need to be treated to see one additional adverse event?▼

The number needed to harm (NNH) was 29, meaning that for every 29 children receiving combination therapy, one additional neuropsychiatric adverse event would occur compared to ICS alone.

Should clinicians avoid prescribing montelukast with ICS in children?▼

The authors recommend caution in high-risk populations but do not advise against use, as the results were not statistically significant. They call for prospective validation studies to clarify the risk.

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References

  1. 1.Yang Q, Guo C, Yu X, Liu X, Xie J, Liu K. "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.." The Journal of asthma : official journal of the Association for the Care of Asthma, 2026. PMID: 42501004 DOI: 10.1080/02770903.2026.2706354
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.