Abstract
We identified the first-generation antihistamine hydroxyzine as the earliest and most frequently prescribed drug affecting the central nervous system in children under the age of 5 years in the province of British Columbia, Canada (1. 1% prevalence). Whereas, the antagonism of H1-receptors exerts anti-pruritic effects in atopic dermatitis and diaper rash, animal studies suggest an adverse association between reduced neurotransmission of histamine and psychomotor behavior. In order to investigate hydroxyzine safety, we characterized the longitudinal patterns of hydroxyzine use in children under the age of 5 years and determined mental- and psychomotor disorders up to the age of 10 years. We found significantly higher rates of ICD-9 and ICD-10 codes for disorders such as tics (307), anxiety (300) and disturbance of conduct (312) in frequent users of hydroxyzine. Specifically, repeat prescriptions of hydroxyzine compared to a single prescription show an increase in tic disorder, anxiety and disturbance of conduct by odds ratios of: 1.55 (95%CI: 1.23–1.96); 1.34 (95%CI: 1.05–1.70); and 1.34 (95%CI: 1.08–1.66) respectively in children up to the age of 10 years. Furthermore, a non-significant increased trend was found for ADHD (314) and disturbance of emotions (313). This is the first study reporting an association between long-term neurodevelopmental adverse effects and early use of hydroxyzine. Controlled studies are required in order to prove a causal relationship and to confirm the safety of hydroxyzine in the pediatric population. For the time being, we suggest the shortest possible duration for hydroxyzine use in preschool-age children.
Highlights
Between birth and 5 years of age, the human brain exhibits its fastest rate of development [1]
The result of clinical cohort studies in children at school age and adolescents with allergic rhinitis suggests that use of sedative antihistamine drugs has a more negative impact on learning and academic performance compared to allergic rhinitis alone or if non-sedative second-generation antihistamine drugs are used [4, 5]
We found that the repetitive use of the first-generation antihistamine drug hydroxyzine in children of preschool age, was associated with elevated rates for tic disorder, anxiety and disorder of conduct up to the age of 10 years, by odds ratios of 1.55 (95%CI: 1.23–1.96); 1.34 (95%CI: 1.05–1.70) and 1.34 (95%CI: 1.08–1.66) respectively
Summary
Between birth and 5 years of age, the human brain exhibits its fastest rate of development [1]. The original purpose of our study was the assessment of psychotropic drug use and Histamine Neurotransmission During Child Development associated diagnosis patterns in children under the age of 5 years. Due to the increasing prevalence of allergic rhinitis in children of school age and in adolescents, studies were conducted to address the impact of disease and medication on learning and academic achievement. The result of clinical cohort studies in children at school age and adolescents with allergic rhinitis suggests that use of sedative antihistamine drugs has a more negative impact on learning and academic performance compared to allergic rhinitis alone or if non-sedative second-generation antihistamine drugs are used [4, 5]
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