First-Generation Antihistamines for Children: Can They Increase Seizure Risk?

The use of first-generation antihistamines for children aged 6 to 24 months can lead to the increased likelihood of seizures, according to study findings published in JAMA Network Open.

Little drug safety data exists on the use of first-generation antihistamines in children younger than 2 years, and antihistamines have been noted to trigger acute symptomatic seizures.

For the study, researchers aimed to examine the association between the prescription of first-generation antihistamines and seizures in young children in a retrospective cohort using data from the National Health Insurance Service database in Korea. They obtained data for 1,893,314 individuals born between January 2002 and December 2005 and followed up until December 2019.

The case-crossover study design utilized each participant as their own control to eliminate confounding factors and analyzed short-term exposure effects on acute events. The index date was the date of seizure occurrence, and the hazard period was the 15 days preceding the index date in which a first-generation antihistamine was prescribed. Control period 1 was defined by prescriptions 31 to 45 days before the index date, and control period 2 was defined by prescriptions 61 to 75 days before the index date.

The population consisted of the 11,729 children within the database who were prescribed first-generation antihistamines before a seizure event. Seizure events were defined as visits to an emergency department with a diagnosis of epilepsy, status epilepticus, or convulsions. The first-generation antihistamines prescribed included chlorpheniramine maleate, mequitazine, oxatomide, piprinhydrinate, and hydroxyzine hydrochloride.

At the index date, 985 participants (31.0%) were aged 6 to 24 months, 1445 participants (45.4%) were aged 25 months to 6 years, and 748 participants (23.5%) were 7 years and older.

During the hazard period 1476 participants (46.4%) were prescribed antihistamines, 1239 participants (39.0%) received antihistamine prescriptions during control period 1, and 1278 participants (40.2%) were prescribed antihistamines during control period 2.

The risk for seizure events during the hazard period was elevated compared to the control periods (adjusted odds ratio [aOR], 1.22; 95% CI, 1.13-1.31). Moreover, new users of antihistamines during the hazard period were also at higher risk for seizure events (aOR, 1.25; 95% CI, 1.14-1.35). Patients aged 6 to 24 months were the only age group with a significantly increased risk for seizure events (22.0%; aOR, 1.49; 95% CI, 1.31-1.70).

Study limitations included the use of insurance data to inform diagnoses which does not include symptom details, the fact that observation was only performed on children visiting the emergency department excluding outpatient clinic data, the inability to verify intake of prescribed antihistamines, and the potential for unmeasured clinical conditions during hazard periods.

“Our results may suggest the need for careful consideration when prescribing antihistamines to infants or patients prone to seizures,” the researchers concluded.