Therapeutic Drug Monitoring in Children and Adolescent Psychiatry – First Results for Atypical Antipsychotic Drugs

Abstract

The psychopharmacotherapy of children and adolescents varies from that of adults due to age-dependent and developmental differences in the pharmacokinetics and pharmacodynamics of psychotropic drugs. The aim of this ongoing study was to examine the relationship between serum concentration, treatment response and adverse effects to elucidate the age-specific therapeutic range of several atypical antipsychotic drugs in children and adolescents under naturalistic conditions. Over a period of 4 years Therapeutic Drug Monitoring (TDM) was routinely performed in children and adolescents with schizophrenic disorders treated with atypical antipsychotic drugs according to the guidelines of the AGNP TDM expert group. The psychopathology was assessed by using the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS), adverse side effects were assessed by the UKU-side effect rating scale. We retrospectively evaluated all TDM-analyses of the atypical antipsychotic drugs risperidone, quetiapine, clozapine, and olanzapine in an unselected sample of paediatric patients with schizophrenic disorders in a standard clinical setting. We found a marked variability of serum concentrations. In 36 patients receiving oral doses of risperidone (mean 4,18mg) 67% of the risperidone serum concentrations were within the recommended concentration ranges for TDM in adults (20–60ng/ml). Only 35% of the serum concentrations of quetiapine in 34 patients were within the recommended ranges for adults (70–170ng/ml), 44% of the patients showed lower serum-levels of quetiapine although 68% received more than the recommended dosage for adults (300–450mg) with a maximum of 1000mg daily. Clozapine therapy with 100 to 600mg daily improved psychotic symptoms in 90,3% of the 32 patients. 47% of clozapine serum concentrations were lower, 25% were higher than the recommended ranges for adults (350–600ng/ml). In the 17 schizophrenic patients receiving olanzapine (2,5–20mg daily) 70,6% of olanzapine serum levels were in the recommended ranges for adults (20–80ng/ml). Our preliminary data of TDM in an average child and adolescent psychiatric population suggest that some therapeutic ranges recommended for adults seem to be quite valid for children and adolescents (e.g. olanzapine), whereas others seem not (e.g. quetiapine). Further studies using larger samples are warranted.