Claudia Mehler-Wex

Introduction: Quetiapine is used frequently in the treatment of children and adolescents with different psychiatric disorders despite not being licensed for this age group. The aim of this observational study was to examine the relationship between dosage, serum concentration and therapeutic response in children and adolescents treated with quetiapine in daily clinical practice. Methods: Steady state trough serum concentrations of quetiapine were measured in 122 children and adolescents as part of a routine TDM-program. The therapeutic effect was assessed by the Clinical Global Impression Improvement subscale (CGI-I) and side effects by the Udvalg for Kliniske Undersogelser-side effect rating scale (UKU). Results: A weak linear relationship between the bodyweight adjusted daily dose (mean (SD); 6.1 (4.1)mg/kg) and serum concentration (mean (SD); 78.5 (93.1) ng/ml) of quetiapine was found (Pearson r²=0.13). The majority (77.9%) of the measured serum concentrations were below, 20.5% within and 1.6% above the therapeutic window (100–500ng/ml) suggested for adults. Serum concentrations were not significantly influenced by gender, smoking-habits or co-medication. 43% of the patients showed very good or good improvement, 48% little improvement, 7% no change and only 2% deteriorated. 45.1% of the patients had side effects; most of them mild. However, no correlation between serum concentration and neither the therapeutic nor side effects was found. Discussion: Our results suggest a lower therapeutic window of quetiapine for children and adolescents and higher dosing than in adult psychiatric patients. Further studies with greater sample sizes and diagnosis-specific as well as age-specific psychometric instruments are needed to confirm our findings.

Introduction and Aims: Aripiprazole is an atypical antipsychotic used in the treatment of children and adolescents with various psychiatric disorders despite limited data on dosing, efficacy and safety in this patient group. In this observational study, the relationship between dosage, serum concentration and clinical outcomes in children and adolescents treated with aripiprazole for different diagnoses such as schizophrenia and Tourette-syndrome was examined. Methods: Steady state trough serum concentrations of aripiprazole were measured in 76 children and adolescents within a routine TDM-service. The therapeutic effect was evaluated with the Clinical Global Impression Improvement Scale (CGI-I) and side effects with the Udvalg for Kliniske Undersogelser-side effect rating scale (UKU). Results: A linear relationship between the body weight-normalized aripiprazole daily dose (mean (SD); 0.19 (0.11)mg/kg) and the serum concentration (mean (SD); 212 (155) ng/ml) was found (Pearson r=0.60). The explained variability was higher in children 2=0.53) than in adolescents (r²=0.33). Serum concentrations were significantly influenced by age (p=0.02) and sex (p=0.02), with children and males showing lower mean serum concentrations, however, there was no significant influence by comedication (p=0.23) or smoking habits (p=0.18). A good or very good therapeutic effect (equivalent to CGI-I 1 or 2) was seen in 46.7% of the patients. Side effects were documented in 55.3%. There was no correlation between serum concentrations and side effects (Spearman ρ=0.07) nor therapeutic effects (Spearman ρ=0.17). Conclusion: Further studies are needed to evaluate our results on larger sample sizes and with more precise information about the patients' characteristics and the course of treatment.