Systematic review and meta-analysis of leukotriene receptor antagonist use and neuropsychiatric risk in adults and childrenAdults on LTRAs show higher neuropsychiatric risk than children in this analysis

Frontiers in Medicine Published April 30, 2026 DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Note age-specific neuropsychiatric risk differences with LTRA use in adults versus children.

This systematic review and meta-analysis examined the association between leukotriene receptor antagonist (LTRA) use and neuropsychiatric risk. The analysis incorporated data from 21 included studies covering overall, pediatric, and adult populations. The primary outcome assessed the link between LTRA use and neuropsychiatric disorders.

In the overall population, the analysis demonstrated a borderline non-significant association with a relative risk of 1.11 and a 95% CI of 0.98–1.26. For the pediatric population, no significant increase in overall risk was observed, with a relative risk of 1.12 and a 95% CI of 0.90–1.39. Conversely, the adult population showed a statistically significant positive association, with a relative risk of 1.30 and a 95% CI of 1.08–1.56.

The authors note that absolute numbers were not reported for these outcomes. The review highlights the importance of age-specific risk assessment in clinical management. Causality was described as an association rather than a definitive causal link. Limitations regarding funding or conflicts were not reported. The certainty of the evidence was not reported in the source material.

This systematic review and meta-analysis looked at 21 studies to examine the link between using leukotriene receptor antagonists, known as LTRAs, and neuropsychiatric disorders. The researchers analyzed data from both adult and pediatric populations to see if the risk was the same for everyone.

The analysis found a borderline non-significant association in the overall group. However, when the data was split by age, the results differed. In the adult population, there was a statistically significant positive association between LTRA use and neuropsychiatric risk. The risk ratio was 1.30 with a 95% confidence interval of 1.08 to 1.56.

In contrast, the pediatric population showed no significant increase in overall risk. The risk ratio was 1.12 with a 95% confidence interval of 0.90 to 1.39. Because the study only shows an association, it cannot prove that the medication caused these events. The authors note that clinical management should include age-specific risk assessment. This review helps doctors understand potential differences in safety between adults and children taking these drugs.

What this means for you:

Adults may have higher neuropsychiatric risk with LTRAs than children, but this analysis shows association only.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

ObjectiveThis study conducted a meta-analysis of previous research to comprehensively evaluate the association between leukotriene receptor antagonists (LTRAs) and the risk of neuropsychiatric disorders, with a specific focus on examining potential variations in this association across different age groups.MethodsA comprehensive search was conducted across multiple databases, including PubMed, Embase, Web of Science and the Cochrane Library, from their inception until 28 April 2025, with no language restrictions applied. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Data analysis was performed using R (version 4.2.2), with results expressed as relative risk (RR) and 95% confidence intervals (CI). Sensitivity analysis was carried out to verify the robustness of the findings. Heterogeneity was quantified using the I2 statistic, while publication bias was evaluated through Egger’s test and visual inspection of funnel plots.ResultsA meta-analysis of the 21 included studies revealed a borderline non-significant association between LTRA use and neuropsychiatric risk in the overall population (RR = 1.11, 95% CI: 0.98–1.26). However, subgroup analysis indicated a statistically significant age-dependent disparity in this risk. Specifically, no significant increase in overall risk was observed in the pediatric population (RR = 1.12, 95% CI: 0.90–1.39). In contrast, a statistically significant positive association was identified in the adult population (RR = 1.30, 95% CI: 1.08–1.56).ConclusionOur findings indicated that LTRA use was associated with a favorable neuropsychiatric safety profile in the pediatric population, but was linked to an increased risk in adults. These results highlighted the need for age-specific risk assessment in clinical management.Systematic Review RegistrationCRD420251042206.

Systematic review and meta-analysis of leukotriene receptor antagonist use and neuropsychiatric risk in adults and childrenAdults on LTRAs show higher neuropsychiatric risk than children in this analysis

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Systematic review and meta-analysis of leukotriene receptor antagonist use and neuropsychiatric risk in adults and childrenAdults on LTRAs show higher neuropsychiatric risk than children in this analysis

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