JAMA Study Reveals 22 Percent Increased Seizure Risk with First-Generation Antihistamines in Young Children

"These findings highlight the importance of prescribing first-generation antihistamines with caution in young children and stress the necessity for additional research to clarify the relationship between these medications and seizure risk," the researchers wrote in JAMA Network Open.

First-generation antihistamines, such as diphenhydramine and chlorpheniramine, are commonly used to treat allergic reactions and symptoms of the common cold. However, their use in young children has come under scrutiny following new findings about their potential neurological side effects.

The frequent use of antihistamines in children to treat common cold symptoms, coupled with their central nervous system effects such as drowsiness, underscores the need to be vigilant about the associated risks. Considering this, Ju Hee Kim, Kyung Hee University School of Medicine, Seoul, Korea, and colleagues aimed to evaluate associations between prescriptions of first-generation antihistamines and seizures in children using a comprehensive and nationwide dataset.

The cohort study employed a self-controlled case-crossover design, utilizing data from the National Health Insurance Service database in Korea. It included children born between 2002 and 2005 who experienced seizure events, as identified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes R56.8, G40, and G41, during their emergency department visits. The follow-up period concluded on December 31, 2019, and data analysis took place from June 3, 2023, to January 30, 2024.

The study focused on prescriptions of first-generation antihistamines as the exposure. The primary outcome was the occurrence of an index seizure event. Odds ratios (ORs) for seizure events were calculated using a conditional logistic regression model. This model compared the risk associated with first-generation antihistamine prescriptions 1 to 15 days before a seizure (the hazard period) with control periods 31-45 days and 61-75 days before the event. Stratified analyses were performed to explore how individual participant characteristics influenced the association.

The study led to the following findings:

• Of 11 729 children who had a seizure event, 3178 (55.9% boys) were identified as having been prescribed antihistamines during the hazard or the control period, but not both.
• Seizure events were predominantly observed in children aged 6 to 24 months (31.0%) and 25 months to 6 years (45.5%).
• During the hazard period, 1476 first-generation antihistamine prescriptions were recorded, in contrast to 1239 and 1278 prescriptions during control periods 1 and 2, respectively.
• After multiple confounder adjustments, first-generation antihistamine prescription was associated with an increased seizure event risk during the hazard period (adjusted OR [AOR], 1.22).
• Stratified subgroup analyses showed consistent results, particularly in children aged 6 to 24 months who were prescribed first-generation antihistamines having a higher risk (AOR, 1.49) than children aged 25 months to 6 years (AOR, 1.11).
• Sensitivity analyses, including adjustment for exposure window periods, evaluation of new first-generation antihistamine prescriptions, comparison of control points from the same period one year prior, and exclusion of individuals using combination drugs, confirmed a similarly high risk.

This cohort study identified a link between antihistamine use and a higher likelihood of seizure events, particularly among children aged 6 to 24 months and other vulnerable groups.

"It is crucial to carefully weigh the benefits and risks when prescribing H1 antihistamines to at-risk infants. Further research is necessary to better understand the relationship between antihistamine prescriptions and seizure risk," the researchers concluded.

Reference:

Kim JH, Ha EK, Han B, et al. First-Generation Antihistamines and Seizures in Young Children. JAMA Netw Open. 2024;7(8):e2429654. doi:10.1001/jamanetworkopen.2024.29654