Neuropsychiatric adverse effects of antihistamine: A nationwide data-based epidemiological study in South Korea

Despite concerns on the major neuropsychiatric side effects for long-term use of H1-receptor antagonist (anti-histamine, AH), one of the major therapeutic tools for allergic diseases, their association has not been investigated well.

This study aimed to assess the association between AH usage and neuropsychiatric disorder (NPD) incidence using the National Health Insurance Service Database.

This study was conducted using data from the National Health Insurance Service Database from January 1st 2002 through December 31th 2017. To enroll the participants who may have history of long-term use of AH, participants having common allergic diseases were enrolled. We defined NPD as diagnosed by a psychiatrist occurring during and after antihistamine use to 6 months thereafter.

A total of 1,488,075 participants were enrolled. No significant association was found between increased AH usage and NPD incidence after adjusting for potential confounding factors in the health screening data. Notably, the 30-89 day AH usage group showed a significantly lower NPD risk in the subgroup analysis in participants aged over 60 years. No other groups within this age category showed a significant increase in risk.

This study suggests that long-term AH use does not significantly increase NPD risk. While this study lacked evaluation of mild neuropsychiatric side effects not requiring psychiatric visits, this study may contribute real-world evidence to the understanding of AHs' long-term neuropsychiatric side effects.