Respiratory drugs and psychiatric adverse events in children and adolescents: a pharmacovigilance study based on the FAERS database

Abstract

The association between respiratory drugs (RDs) and pediatric psychiatric adverse events (pAEs) remains insufficiently characterized. We aimed to characterize pAEs associated with RDs use in pediatric patients. RD-related pAE reports were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Analysis focused on pediatric patients aged 0 to 17 years. Disproportionality analysis was conducted using four algorithms, with a focus on anxiety disorders and symptoms, depressed mood disorders and disturbances, and suicidal and self-injurious behaviors. Descriptive and clinical outcome analyses were performed, along with subgroup analyses to explore potential risk differentials by age and gender. Among 6,994 cases of RD-related pAEs in pediatric patients, 16 drugs with positive signals were identified across all four algorithms, with antiallergics accounting for 75.00%. Montelukast was the most frequently reported drug (n = 6,168), primarily associated with anxiety (21.84%, reporting odds ratio [ROR] = 15.08), depression (15.86%, ROR = 12.90), and suicidal ideation (14.27%, ROR = 13.63). Promethazine demonstrated strong signals for intentional self-injury (62.99%, ROR = 127.36). The highest mortality rates were observed with hydroxyzine (50.94%) and caffeine (50.00%), while oxytetracycline (4/4, 100%) showed the highest proportions of life-threatening events. Montelukast generated signals in all age and gender groups, with the highest disproportionality observed in children aged 0 to 4 years. This study identifies statistical associations between RDs and pAEs in pediatric patients, particularly with montelukast and promethazine. The highest mortality rates were observed with hydroxyzine. These findings provide a foundation for further research but require confirmation through large-scale prospective studies.