{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:41:55Z","timestamp":1772491315656,"version":"3.50.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>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\u20131.96); 1.34 (95%CI: 1.05\u20131.70); and 1.34 (95%CI: 1.08\u20131.66) 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.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.721875","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T09:35:56Z","timestamp":1643362556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Hydroxyzine Use in Preschool Children and Its Effect on Neurodevelopment: A Population-Based Longitudinal Study"],"prefix":"10.3389","volume":"12","author":[{"given":"Hans J.","family":"Gober","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy H.","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce C.","family":"Carleton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s11065-012-9214-1","article-title":"Brain development during the preschool years","volume":"22","author":"Brown","year":"2012","journal-title":"Neuropsychol Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1037\/a0021026","article-title":"Developmentally-sensitive diagnostic criteria for mental health disorders in early childhood: DSM-IV, RDC-PA, and the revised DC: 0-3","volume":"66","author":"Egger","year":"2011","journal-title":"Am Psychol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1097\/WOX.0b013e318186fb3a","article-title":"H1 antihistamines current status and future direction","volume":"1","author":"Simons","year":"2008","journal-title":"World Allergy Organ J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/0924-977X(92)90101-D","article-title":"Seasonal allergic rhinitis and antihistamine effects on children's learning","volume":"71","author":"Vuurman","year":"1993","journal-title":"Ann Allergy."},{"key":"B5","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.jaci.2007.03.034","article-title":"Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case-control study","volume":"120","author":"Walker","year":"2007","journal-title":"J Allergy Clin Immunol."},{"key":"B6","first-page":"193","article-title":"Memory facilitation by histamine","volume":"283","author":"de Almeida","year":"1986","journal-title":"Arch Int Pharmacodyn Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1056\/NEJMoa0907006","article-title":"L-histidine decarboxylase and Tourette's syndrome","volume":"362","author":"Ercan-Sencicek","year":"2010","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.neuron.2013.10.052","article-title":"Histidine decarboxylase deficiency causes Tourette syndrome: parallel findings in human and mice","volume":"81","author":"Baldan","year":"2014","journal-title":"Neuron."},{"key":"B9","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/S0091-6749(99)70389-1","article-title":"Prospective, long-term safety evaluation of the H1-receptor antagonist cetirizine in very young children with atopic dermatitis. 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