Longitudinal cardiometabolic trajectories in children and adolescents in therapy with second-generation...

Second-generation antipsychotics (SGAs) are widely utilized as first-line agents for several pediatric psychiatric and neurodevelopmental conditions, raising critical safety concerns. Although their cardiometabolic risks are well recognized, evidence on their long-term evolution in routine pediatric clinical practice remains limited. This study investigated the longitudinal cardiometabolic trajectories associated with SGA treatment in a real-world pediatric population.

In this prospective, naturalistic, multicenter observational study, 82 children and adolescents initiating SGA treatment were followed for up to 24 months. Anthropometric, metabolic, and cardiovascular parameters were assessed longitudinally, and linear mixed-effects models were used to evaluate time-dependent changes and differences between treatment groups.

Retention rates and a low incidence of adverse event-related discontinuations suggested acceptable overall tolerability. Longitudinal analysis revealed significant increases in BMI, insulin and HOMA-IR whereas aggregate cardiovascular parameters did not exhibit statistically significant changes. Risperidone was associated with greater increases in waist circumference, prolactin, total cholesterol and ALT levels compared with aripiprazole. Furthermore, patients with Autism (ASD) exhibited significantly greater increases in BMI, waist circumference, and systolic blood pressure compared to non-ASD youth.

While demonstrating an acceptable tolerability profile, risperidone and aripiprazole were associated with different cardiometabolic and endocrine variations over a 24-month period in this real-world pediatric cohort. These findings should be interpreted within the context of the study's observational nature and of potential confounding factors (e.g., unmeasured dietary, physical activity, and pubertal factors), highlighting the clinical necessity of longitudinal monitoring in children and adolescent patients.