Antipsychotics Dominate Adverse Drug Reaction Reports in Children Across Two Global Databases

A large retrospective analysis of two of the world’s biggest drug safety databases has mapped how often the adverse reactions that make certain drugs ‘potentially inappropriate’ for children actually show up in real-world reports. The study, published in BMC Pediatrics, mined the United States FDA Adverse Event Reporting System (FAERS) and the European EudraVigilance database for reports filed between 2020 and 2025 involving patients under 18 years of age. The medications in focus were those on the KIDs list — the Key Potentially Inappropriate Drugs in Pediatrics — a catalog of medicines that warrant particular caution in children because their risk-benefit balance is considered unfavorable in specific age groups.

Children are considered uniquely vulnerable to adverse drug reactions owing to developmental pharmacokinetics, and pediatric pharmacotherapy frequently involves off-label use, both of which the study’s authors cite as factors accompanying advances in pediatric treatment. The researchers asked a deceptively simple question: when a drug appears on the KIDs list because of a specific flagged adverse reaction, how often does that exact reaction get reported in children taking the drug? To answer it, they counted individual case safety reports (ICSRs) in which the medication of interest appeared as a primary or secondary suspect — the pharmacovigilance convention for a drug considered potentially causal in a reported event. For each drug, they distinguished between all adverse events reported and the specific ‘adverse drug reaction of interest’ that had earned the drug its KIDs listing for a given age group.

After deduplication, the analysis encompassed 8,276 reports in FAERS and 9,114 in EudraVigilance. The age distribution differed between the databases: adolescents aged 12 to 17 accounted for 54.42 percent of FAERS reports and 42.03 percent of EudraVigilance reports.

The headline finding was that the predefined reactions of interest were documented in 1,427 FAERS reports, or 17.24 percent of the total, and in 521 EudraVigilance reports, or 5.72 percent. In other words, in a meaningful minority of pediatric cases involving these drugs, the very adverse events that triggered their cautionary designation were being reported to regulators. The study design cannot establish why the proportions differ between the two systems.

Across both databases, drugs acting on the central nervous system — particularly atypical antipsychotics — accounted for the majority of reported reactions. Metabolic disturbances and extrapyramidal symptoms were the most frequently observed. Among the metabolic findings, hyperprolactinemia emerged as a prominent signal, alongside weight gain and dyslipidemia.

The antipsychotics were not the only drugs leaving fingerprints in the data. Among medications acting outside the central nervous system, montelukast — the widely used asthma and allergy drug — contributed substantially to reports of sleep disturbance.

The analysis also captured serious adverse events, including reports of fatal outcomes, involving the neurological, respiratory, metabolic and hematological systems. Because spontaneous reporting databases capture suspected rather than confirmed causal relationships, and reporting is subject to underreporting and bias toward unusual or severe events, these findings describe patterns of reported reactions rather than measured incidence rates in the pediatric population.

The consistency of the adverse reaction patterns across two complementary pharmacovigilance systems strengthens the study’s central message: children prescribed potentially inappropriate medications are, in real-world reporting practice, experiencing the harms those designations anticipate. The authors frame the results as underscoring the need for judicious prescribing, close monitoring, and strengthened pharmacovigilance to improve medication safety in children.

Subject of Research: Reported adverse drug reaction patterns for potentially inappropriate medications in children using FAERS and EudraVigilance

Article Title: Adverse drug reaction patterns associated with potentially inappropriate medications in children: insights from two global pharmacovigilance databases

Article References: Mariam, H., Bharathi R, P., & Kamath, A. (2026). Adverse drug reaction patterns associated with potentially inappropriate medications in children: insights from two global pharmacovigilance databases. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07896-y

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07896-y

Keywords: pediatric pharmacovigilance, adverse drug reactions, KIDs list, FAERS, EudraVigilance, atypical antipsychotics, hyperprolactinemia, weight gain, dyslipidemia, montelukast, drug safety, Adverse