Systematic review and meta-analysis of leukotriene receptor antagonist use and neuropsychiatric risk in adults and children

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.