Endocrine and Growth Consequences of Antiseizure Medications and Antipsychotics in Paediatric Patients: A Critical Narrative Review
Ashraf T. Soliman *
Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar.
Fawzia Alyafei
Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar.
Nada Alaaraj
Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar.
Noor Hamed
Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar.
Shayma Ahmed
Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar.
*Author to whom correspondence should be addressed.
Abstract
Children and adolescents receive antiseizure medications and antipsychotics for prolonged periods during the developmental window in which linear growth, bone mineral accrual, pubertal maturation and metabolic set points are established. Endocrine and auxological adverse effects therefore carry consequences that differ qualitatively from those observed in adults, yet the paediatric evidence base has developed unevenly across drug classes, outcome domains and world regions. This critical narrative review evaluates the strength, consistency and methodological quality of evidence linking the two most widely prescribed classes of long-term paediatric neuropsychopharmacology to disturbances of growth, bone, reproductive function, energy metabolism and thyroid physiology. Literature was identified through structured searching of biomedical and multidisciplinary scholarly indexes, supplemented by citation tracking, with a final search date of 30 May 2026. Evidence was appraised for design adequacy, comparator quality, control of confounding by indication and developmental stage, outcome validity and generalisability, and was synthesised thematically around mechanisms, outcome domains and problems of causal attribution. The available evidence supports several robust conclusions: antipsychotics produce agent-specific and dose-related increases in adiposity and prolactin that are larger in antipsychotic-naive young people than in adults; valproate is associated with hyperandrogenic features and adverse metabolic change in adolescent girls; and both classes are associated with reductions in bone mineral density and vitamin D status of modest average magnitude. Confidence weakens considerably when biochemical surrogates are translated into clinically meaningful endpoints such as fracture, final adult height, fertility and cardiometabolic disease, because trials are short, cohorts are small and rarely control simultaneously for underlying disease, disability, nutrition and pubertal stage. Discrepancies among studies are frequently attributable to differences in pubertal staging, comparator selection and definitions of biochemical thresholds rather than to genuine pharmacological divergence. Priorities include developmentally anchored longitudinal cohorts with skeletal and auxological endpoints, harmonised outcome definitions, pragmatic mitigation trials and evidence-based monitoring pathways that are feasible in routine paediatric care.
Keywords: Antiseizure medication, second-generation antipsychotics, paediatric endocrinology, hyperprolactinaemia, bone mineral density, valproate, drug-induced weight gain, pubertal development