Association and mechanism of montelukast on sleep disorders: insights from NHANES 2005–2018 data analysis and a network pharmacology study

BACKGROUND: Studies have suggested associations between montelukast and increased risks of sleep disorders, including overall sleeping problems and insomnia. However, the results of observational studies are not consistent. Understanding these associations is crucial, particularly in patients solely diagnosed with allergic rhinitis, where montelukast use remains prevalent. OBJECTIVE: This study aimed to assess whether montelukast exposure is associated with sleep disorders and elucidate the possible molecular mechanism. METHOD: We conducted a cross-sectional study of 16,520 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Multivariable regression was used to evaluate the association between montelukast exposure and sleep disorder. Network pharmacology was conducted to identify the mechanisms of montelukast on sleep disorders. RESULTS: Montelukast exposure had a higher prevalence of sleep disorders (25.28%). In a multivariable logistic regression model adjusted for sociodemographic, behavioral, and health characteristics, montelukast exposure was associated with sleep disorders (odds ratio [OR]: 1.72; confidence interval [CI]: 1.32-2.26). Network pharmacology was identified 39 intersection targets and 17 core targets of montelukast on sleep disorders. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested montelukast mainly works through multiple pathways in chemical carcinogenesis-receptor activation, cancer, estrogen signaling pathway, etc. CONCLUSIONS: The study implies a potential positive association between long-term montelukast exposure and sleep disorders through multi-faceted mechanisms. It is suggested that attention be given to the possibility of sleep disorders in patients undergoing prolonged montelukast therapy.