Antipsychotic drug toxicology in children

INTRODUCTION: There is an increasing use of antipsychotic drugs, particularly those of second- and third-generation, for a wide range of behavioral and affective disorders in pediatric and psychiatric practice. Limited data are available, however, regarding their safety and effectiveness, although children may be more vulnerable than adults to antipsychotic adverse effects because of developmental physiological changes that may affect their pharmacodynamic and pharmacokinetic profiles. AREAS COVERED: This review covers the antipsychotics now specifically approved in major markets for children as well as those that are used in these patients for unapproved or off-label indications taking into account the potential differences in drug disposition and metabolism among children, adolescents and adults. MEDLINE and EMBASE international databases were searched for studies concerning the pharmacokinetics, efficacy and safety of first-, second- ('atypical') and third-generation antipsychotic agents. EXPERT OPINION: Few studies have systematically monitored the safety of antipsychotics in young populations. Data concerning long-term side effects are especially limited, and a systematic benefit-risk evaluation is needed. When prescribing antipsychotics, physicians should, therefore, monitor patients closely for metabolic adverse events, hyperprolactinemia, extrapyramidal symptoms and corrected QT prolongation. Dose selection should include a careful consideration of the drugs' pharmacokinetic profiles and, when these are lacking therapeutic drug monitoring should be implemented as it is often a valid tool to optimize pediatric psychiatric practice.