Therapeutic drug levels of second generation antipsychotics in youth: a systematic review

In children and adolescents, the prevalence rate of mental illness is claimed to be as high as 10-20%. Effective pharmacological treatments are available for use in children, adolescents, and adults; however, most of what is known about the effects of these treatments has been confirmed in clinical studies involving adults only. Second generation antipsychotic drugs (SGAs) are the most common class of antipsychotic medication used in pediatric populations, and these drugs are increasingly being used for disorders other than psychosis. Many SGAs are routinely used in pediatric care, and the vast majority of use in this population is off label. Children, adolescents, and adults differ in age, weight, height, and metabolism, which may lead to pharmacokinetic differences in how drugs ultimately affect target tissues. The aim of this review is to summarize and evaluate the literature that investigated blood plasma levels of SGAs in youth. Plasma levels were assessed in relation to their administered dose, indication, and therapeutic range (if known). Studies were limited to those evaluating oral administration only. A systematic electronic database search for peer-reviewed articles published between 2000 and 2013 was conducted. Twenty-one articles were included in the review. Additional articles for discussion were also included throughout the article. The only SGA that may require routine therapeutic drug monitoring (TDM) in youth given the current body of research is clozapine. Highly variable results were seen in studies of aripiprazole, olanzapine, and risperidone, indicating that more research is needed on plasma levels with these drugs. Quetiapine maintained a similar profile to that found in adults, with no dosage adjustments or indications of TDM. TDM may be indicated in any circumstance in which cytochrome P450 inhibitors or inducers are coprescribed. Further research is required for establishing a sounder safety profile for SGA use in the pediatric population.