Safety and Pharmacokinetics of Atypical Antipsychotics in Children and Adolescents

Pediatric behavioral and affective disorders often require antipsychotic therapy, in combination with psychotherapeutic interventions, for their treatment and stabilization. Although pharmacotherapy can include either typical or atypical antipsychotics, the latter are generally preferred because of their apparently lower risk of adverse effects. Recent controlled trials have demonstrated the efficacy of some of these agents (including aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone) in adolescent schizophrenia and children or adolescent bipolar mania, or to treat severe aggression and self-injury in the context of autism in children and adolescents. Although few studies have systematically monitored their short- and, more importantly, long-term safety, current evidence indicates that sedation, hyperprolactinemia, and metabolic abnormalities such as excess weight gain, diabetes, and related cardiovascular effects were clinically relevant adverse effects in young patients, with the individual agents differing in their propensity to induce these effects. When prescribing antipsychotics for children and adolescents, physicians should therefore be aware of the specific adverse effect profiles and patients should be closely monitored for the short- and long-term development of adverse events. In pediatric patients, the starting dose, titration plan, and maintenance dose of antipsychotics must be based on their pharmacokinetics and metabolism, as in adults. Because there are significant individual differences in drug and active metabolite(s) pharmacokinetics and metabolism, which may be further affected by a number of confounding factors (including demographic variables, phenotype and drug interactions), therapeutic drug monitoring may be a valid tool for individualizing dosage, but its interpretation should also take account of changes in pharmacodynamic sensitivity with the development during childhood and adolescence.