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Hydroxyzine Use in Preschool Children and Its Effect on Neurodevelopment: A Population-Based Longitudinal Study
Open accessAbstract
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.
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Long-term use of antihistamines in young children has yet to be studied.
“Since the long-term use of these medications in young children has yet to be studied, they are not recommended for long-term use for young children [67].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [67]
The Introduction describes a prospective long-term safety study of cetirizine in children aged 1–2 years, with developmental outcomes assessed up to 18 months after treatment stopped. The paper also investigates repetitive hydroxyzine use in children under five. Thus, the blanket claim that long-term antihistamine use in young children has yet to be studied is contrary to this source, although the source says evidence for hydroxyzine specifically was limited. (LLM, conf=0.88)
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Cites
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
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Manter, M. A., Birtwell, K. B., Bath, J., Friedman, N. D. B., Keary, C. J., Neumeyer, A. M., Palumbo, M. L., Thom, R. P., Stonestreet, E., Brooks, H., et al. (2025) · BMC Medicine · doi:10.1186/s12916-024-03814-0 · Cited by 51
“As noted previously, the safety of long-term use of antihistamines in young children has yet to be studied, and thus, hydrox-yzine is not recommended for long-term use for young children [67].”
Metadata
- Authors
- Gober, H. J., Li, K. H., Yan, K., Bailey, A. J., & Carleton, B. C.
- Affiliations
- University of British Columbia (CA)
- Provincial Health Services Authority (CA)
- Corresponding author
- Gober, Hans J.
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2022-01-28
- Volume
- 12
- Pages
- 721875-721875
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC8832122
- OpenAlex
- W4210282834
- Cited by
- 15
- References
- 1
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 3 · 2022: 1
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Provincial Health Services Authority
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- hydroxyzine, antihistamines, drug safety in children, preschool children, tic disorders, anxiety, conduct disorder, attention deficit hyperactivity disorder, histamine, H1 receptor antagonism, atopic dermatitis, diaper dermatitis, repeat prescriptions, drug exposure duration
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