Young children prescribed first-generation antihistamines have a 22% higher risk of seizures, with the greatest risk observed in those aged 6 to 24 months, according to a study published in JAMA Network Open.
The cohort study, using data from the National Health Insurance Service database, examined the association between first-generation antihistamine prescriptions and the risk of seizures in young children. Of the 11,729 children who experienced a seizure event, 3,178 (55.9% male) received first-generation antihistamine prescriptions during either the hazard or control periods. The age breakdown showed that 31.0% (985 children) were between 6 and 24 months, 45.5% (1,445 children) were between 25 months and 6 years, and 23.5% (748 children) were 7 years or older.
Using a self-controlled case-crossover design, researchers compared first-generation antihistamine prescriptions in the 1 to 15 days before a seizure (hazard period) with prescriptions during control periods (31-45 and 61-75 days before the event). A total of 1,476 first-generation antihistamine prescriptions were recorded during the hazard period, compared to 1,239 and 1,278 during control periods 1 and 2, respectively.
Results indicated a significant increase in seizure risk among children aged 6 to 24 months, with an adjusted odds ratio (AOR) of 1.49, (95% confidence interval [CI], 1.31-1.70), compared to an AOR of 1.11 (95% CI, 1.00-1.24) for those aged 25 months to 6 years. This increased risk may be associated with the ability of first-generation antihistamines to cross the blood-brain barrier, as suggested by previous research linking these medications to central nervous system activity and seizure susceptibility. A significant difference between age groups was noted, with the highest risk found in the 6 to 24-month age group (P = .04 for interaction). For new users of first-generation antihistamines, the AOR for seizure events was 1.25 (95% CI, 1.14-1.35).
The sensitivity analysis showed an increased risk of seizures with first-generation antihistamine prescriptions in alternative time frames, with an AOR of 1.25 (95% CI, 1.15-1.36) in the 10-day window and 1.36 (95% CI, 1.23-1.51) in the 5-day window. These findings, published in JAMA Network Open, underscore the importance of exercising caution when prescribing first-generation antihistamines to young children, particularly those younger than two years of age, due to the increased seizure risk.
The study authors noted several limitations, including that seizure information was obtained only from primary diagnoses using insurance data, without details on seizure symptoms. Only children visiting the emergency department were observed, excluding those treated in pediatric outpatient clinics. Additionally, the actual intake of prescribed antihistamines couldn't be verified due to the nature of the database.
This research was supported by a grant from the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea.
The authors reported no conflicts of interest.
