Hydroxyzine Use in Preschool Children and Its Effect on Neurodevelopment: A Population-Based Longitudinal Study

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.

Off-label medications in the treatment of hospitalized children with atopic dermatitis

“…Recent studies showed a possible connection between first-generation antihistamine treatment and a higher rate of attention-deficit/hyperactivity symptoms in children with AD, therefore the authors do not recommend their long-term use [10,17]. Gober et al [18] showed a statistically significant association between neurodevelopmental adverse effects and use of hydroxyzine in children younger than 5 years of age. Majority of first-generation antihistamines have itch as their registered indication and in our cohort they were used in almost 44% (120) of patients.…”

Mental health comorbidity in youth with atopic dermatitis: A narrative review of possible mechanisms

“…The impact of systemic antihistamine use early in life on children's psychological and behavioral development has also been explored. Studies have found higher rates of ADHD symptoms 7,38 as well as tic disorders, anxiety, and behavioral problems 39 in youth who were prescribed systemic antihistamines during early childhood. Fuhrmann and colleagues 38 found while children without AD who were exposed to systemic antihistamines had a 35% increased risk of developing ADHD symptoms compared to children without AD or systemic antihistamine exposure, the risk among children with AD and antihistamine exposure was 47%, indicating both antihistamine use and other factors likely contribute to the development of ADHD symptoms among children with AD.…”