Neurological Adverse Effects Associated With Commonly Used H1‐Antihistamines: A Narrative Review of Age‐Stratified Risk Profiles in Paediatric and Geriatric Populations

The widespread use of the most common H1‐antihistamines across all age groups highlights the need to understand the neurological safety profile of these medicines. Although their therapeutic value is well established, their neurological adverse effects remain underexplored in the context of lifespan. In this narrative review, we synthesised mechanistic, clinical, and pharmacovigilance evidence from PubMed, Scopus, and the Web of Science to examine the pharmacological mechanisms of H1‐antihistamines, their neurological risks, and age‐stratified vulnerabilities in paediatric and geriatric populations. Google Scholar was additionally searched to capture relevant grey literature. Both preclinical and clinical studies were included, focusing on mechanistic insights, adverse event reports, and age‐specific analyses. Given the heterogeneity of the study designs and outcomes, formal systematic review methods and meta‐analysis were not performed. First‐ and second‐generation H1‐antihistamines exhibit distinct central nervous system effects owing to differences in blood–brain barrier penetration and receptor selectivity. In children, the risks include paradoxical excitation, cognitive impairment, and seizures, whereas older adults are more prone to sedation, delirium, and falls. Across age groups, the risk is further modulated by dosage, comorbidities, and polypharmacy. Despite the accumulating evidence, important gaps remain in long‐term safety studies and mechanistic research. Overall, H1‐antihistamines exert age‐dependent neurological adverse effects mediated by pharmacodynamic and pharmacokinetic factors, and a clearer understanding of these risks is essential for safer prescribing in paediatric and geriatric populations, with further research needed to guide evidence‐based clinical recommendations.