How can we better address the pharmacokinetics of antipsychotics in children and adolescents?

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Abstract
Despite a steady increase of antipsychotic prescriptions in children and adolescents, knowledge about pharmacokinetics and dosing of antipsychotics in children and adolescents remains limited. We discuss seven issues with major impact on the pharmacokinetics of antipsychotics in youth: estrogens, ii) obesity, iii) ethnicity, iv) smoking, v) inflammation, vi) drug-drug interactions (DDIs), and vii) pharmacogenetics. Despite their major impact, these issues have not been adequately considered in the context of dosing algorithms for antipsychotics in youth. A simple tool to quantify the impact of these pharmacokinetics issues on antipsychotics is therapeutic drug monitoring (TDM), which refers to the quantification of the prescribed medication in the blood of the patients, as a surrogate of the peripheral antipsychotic exposure. We also provide summary tables extrapolated from the adult literature on metabolism, therapeutic reference ranges (TRRs) and DDIs. Despite considerable experience with TDM for antipsychotics in the management of other patient subgroups, TDM use for antipsychotics in children and adolescents may be limited with TRRs invariably being extrapolated from adult patients. Advancing TDM knowledge is expected to help clinicians address the special properties of pharmacokinetics of antipsychotics and ultimately enable antipsychotic dose individualization in youth.

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