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First-generation antihistamines may increase the risk of seizures in young children
Last reviewed: 02.07.2025
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In a recent study published in JAMA Network Open, researchers assessed the association between first-generation antihistamine prescriptions and the risk of seizures in children.
First-generation antihistamines, originally used as tranquilizers and antipsychotics, are now used to treat cold symptoms and reduce itching in children. These drugs can cross the blood-brain barrier (BBB) and affect brain wave activity, especially in children under two years of age. Research suggests that first-generation antihistamines can cause symptomatic seizures in adults and affect electroencephalographic activity and seizure thresholds. Animal models support a link between antihistamines and epileptic seizures.
In this retrospective cohort study, researchers examined whether acute administration of first-generation antihistamines increases the risk of seizures in children. The analysis was conducted using data from the National Health Insurance Service of Korea (NHIS). Participants were children born between January 1, 2002, and December 31, 2005, who visited emergency departments for seizures.
Children with missing birth records, those who experienced seizures before six months of age, and those who were not prescribed first-generation antihistamines before the seizure were excluded.
The study included the use of International Classification of Diseases, Tenth Revision (ICD-10) codes for the diagnosis of seizures. Data analysis was completed on December 31, 2019, and data were processed between June 3, 2023 and January 30, 2024. The children themselves were used as controls in the study.
The study exposure included first-generation antihistamines, and the primary outcome was seizure occurrence. A multivariable conditional logistic regression model estimated adjusted odds ratios (AORs) for seizures, adjusting for age, sex, economic status, place of residence, perinatal conditions, and season.
Among 11,729 children who developed seizures, 3,178 (56% boys) were prescribed antihistamines during the risk period or the control periods, but not both.
Seizures occurred most frequently in children aged six months to two years (31%) and 25 months to six years (46%). In the 15 days before seizure onset, 1,476 first-generation antihistamines were prescribed, compared with 1,239 prescriptions in the first control period and 1,278 prescriptions in the second control period.
After adjustment for confounding factors, first-generation antihistamine use was associated with an increased risk of seizures during the risk period (AOR 1.2). Subgroup analyses showed similar results, particularly among children aged six months to two years, who had a higher risk of seizures (AOR 1.5) compared with children aged 25 months to six years (AOR 1.1). Sensitivity analyses confirmed the main results.
The study found that prescribing first-generation antihistamines increased the risk of seizures in children by 22%, especially in children aged six months to two years. These findings highlight the importance of careful and judicious use of first-generation antihistamines in young children. More research is needed to determine the relationship between prescribing antihistamines and the risk of seizures.