Endocrine and Growth Effects of Antipsychotic and Antiepileptic Medications in Children and Adolescents

Background: Antipsychotic and antiepileptic medications are increasingly prescribed to children and adolescents for psychiatric, neurodevelopmental, and seizure disorders. Because puberty, bone mineral accrual, and growth velocity are highly hormone-dependent, disruptions to neuroendocrine pathways during this stage can lead to clinically significant and potentially irreversible consequences. Despite common use, endocrine effects are under-recognized and inconsistently monitored in pediatric practice.

Objective: To evaluate endocrine and growth abnormalities associated with antipsychotic and antiepileptic medications in children and adolescents over the past 25 years and to highlight clinical monitoring strategies that reduce risk.

Methods: A literature search of PubMed, Scopus, and Google Scholar identified studies published from January 2000 to January 2025 evaluating endocrine or growth outcomes in patients under 18 years treated with antipsychotic or antiepileptic medications. Observational studies, randomized trials, and meta-analyses with extractable endocrine markers were included. Findings were synthesized narratively due to heterogeneity in outcome reporting.

Results: Second-generation antipsychotics (SGAs) induce rapid and substantial metabolic effects. Olanzapine and risperidone consistently caused early weight gain, increasing BMI-SDS within the first weeks of therapy, accompanied by rising triglycerides, insulin resistance, and impaired glucose tolerance. Risperidone and paliperidone produced the highest prevalence of hyperprolactinemia, resulting in menstrual irregularities, galactorrhea, gynecomastia, and suppressed pubertal progression in susceptible youth. Chronic antipsychotic exposure was associated with reduced bone mineral density and lower IGF-1 activity, particularly when hyperprolactinemia persisted during adolescence. Aripiprazole demonstrated a more favorable endocrine profile with minimal prolactin elevation and lower obesity risk.

Antiepileptic medications showed drug-specific endocrine toxicity. Hepatic enzyme-inducing agents (carbamazepine, phenytoin, phenobarbital) led to increased metabolism of thyroid hormones and vitamin D, contributing to subclinical hypothyroidism, impaired bone mineralization, and higher fracture risk. Valproate was strongly linked to central adiposity, insulin resistance, hyperandrogenism, and menstrual dysfunction in pubertal females. Topiramate often resulted in appetite suppression and metabolic acidosis with negative effects on bone health. Levetiracetam and lamotrigine generally demonstrated endocrine-neutral profiles, making them preferred options when hormonal vulnerability is anticipated.

Conclusion: Antipsychotic and antiepileptic medications impose measurable endocrine and growth burdens in children and adolescents, with metabolic, prolactin-mediated, thyroid-related, and bone health complications varying by drug class and mechanism. Routine monitoring of weight trajectory, puberty, thyroid markers, gonadal hormones, vitamin D status, and bone health is essential to minimize long-term developmental consequences. Treatment decisions should incorporate endocrine risk stratification and early preventive interventions to optimize patient outcomes.