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

Jin Youp Kim,^1,2,3† Zio Kim,^4† Su Hwan Kim,^5,6† Kyung-Lak Son,⁷ Chae-Seo Rhee,^8-11* Hyung-Jin Yoon^2,4,12*

Affiliations:
¹ Department of Otorhinolaryngology–Head and Neck Surgery, Ilsan Hospital, Dongguk University, Goyang, Gyeonggi, South Korea
² Interdisciplinary Program of Medical Informatics, Seoul National University College of Medicine, Seoul, South Korea
³ Sensory Organ Research Institute, College of Medicine, Dongguk University, Gyengju, South Korea
⁴ Interdisciplinary Program of Bioengineering, Seoul National University College of Engineering, Seoul, Republic of Korea
⁵ Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea
⁶ Department of Information Statistics, Gyeongsang National University, Jinju, Gyeongsangnam-do, South Korea
⁷ Department of Psychiatry, Ilsan Hospital, Dongguk University, Goyang, Gyeonggi, South Korea
⁸ Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea
⁹ Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul, South Korea
¹⁰ Institute of Allergy and Clinical Immunology and
¹¹ Sensory Organ Research Institute, Seoul National University Biomedical Research Center, Seoul, South Korea
¹² Medical Big Data Research Center, Seoul National University Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea

^†These authors contributed equally to this work.
*These authors contributed equally to this work as senior authors.

Abstract

Background: 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.
Objective: This study aimed to assess the association between AH usage and neuropsychiatric disorder (NPD) incidence using the National Health Insurance Service Database.
Methods: This study was conducted using data from the National Health Insurance Service Database from
January 1^st 2002 through December 31^th 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.
Results: 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.
Conclusion: 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.
Key words: Antihistamine, Psychiatric Disorders, Drug Side Effects, Health Insurance, Allergic Diseases