Value of a web-based pediatric drug information system to prevent serious adverse drug reactions in child and adolescent psychiatry.

Psychotropic drugs are frequently prescribed 'off-label' to children and adolescents and carry the risk of serious adverse drug reactions (sADR). We examined the frequency of sADRs of psychotropic drugs in pediatric inpatients and explored their potential preventability through following the recommendations of a web-based pediatric drug information system (PDIS). The potential socio-economic impacts of using this online system is also addressed. Routine clinical data from all inpatients treated in a child and adolescent psychiatry department between January 2017 and December 2018 were retrospectively examined for the occurrence of sADRs as defined by the European Medicines Agency. The preventability of the sADRs was assessed based on the information of the PDIS. Furthermore, the expected prolongation of the hospital stay due to sADRs was calculated as well as the associated treatment costs. The study was supported by the Innovation Fund of the Joint Federal Committee, grant number 01NVF16021. In total, 1036 patients were screened of whom 658 (63.5%) received psychopharmacological treatment. In 53 (8.1%) of these patients 54 sADRs were documented, of which 37 sADRs were identified as potentially preventable through PDIS. Mitigating sADR through PDIS would likely have prevented prolonged hospital stays and conferred considerable savings for health insurance companies. PDIS provides systematic and evidence-based information about pediatric psychopharmacotherapy and helps to prevent prescribing errors. Therefore, PDIS is a useful tool to increase drug therapy safety in child and adolescent psychiatry. Further prospective studies are needed to confirm the results.

Therapeutic drug monitoring of children and adolescents treated with aripiprazole: observational results from routine patient care.

Although aripiprazole is one of the most used antipsychotics, knowledge about serum concentrations in children and adolescents is scarce and age-specific therapeutic ranges have not been established yet. Data of a routine therapeutic drug monitoring service were analyzed in order to evaluate the relationship between dose and serum concentration of aripiprazole in children and adolescents. The study also aimed to evaluate whether the therapeutic reference range defined for adults with schizophrenia (100-350 ng/ml) is applicable for minors. Data from 130 patients (aged 7-19 years) treated with aripiprazole for different indications in doses of 2-30 mg/day were evaluated. Patient characteristics, doses, serum concentrations and therapeutic outcome were assessed by standardized measures. A positive mean correlation between body weight-corrected daily dose and aripiprazole concentration was found (rp = 0.59, p < 0.001) with variation in dose explaining 35% of the variability in serum concentrations. Girls had on average 41% higher dose-corrected concentrations than boys (244.9 versus 173.4 mg/l; p = 0.006). Aripiprazole concentrations did not vary with co-medication (p = 0.22). About 70% of all measured serum concentrations were within the recommended therapeutic range for adults. Using a calculation method in all responding patients with an ICD-10 F2 diagnosis for a rough estimation of a preliminary therapeutic window also demonstrated a similar therapeutic range of aripiprazole in minors (105.9-375.3 ng/ml) than for adults. If confirmed in larger samples and more controlled study designs, these data may contribute to the definition of a therapeutic range of aripiprazole concentrations in children and adolescents.

Relationship Between Daily Dose, Serum Concentration, and Clinical Response to Quetiapine in Children and Adolescents with Psychotic and Mood Disorders.

Introduction In child and adolescent psychiatry, therapeutic drug monitoring (TDM) is strongly recommended. However, therapeutic ranges (TR) are defined only for adults. The objectives of this naturalistic study were to assess the relationships between serum quetiapine concentration, daily dose, and clinical outcomes as well as the determinants of pharmacokinetic variability. Furthermore, it was elucidated whether the recommended TR for adult patients with psychotic disorders is valid for children and adolescents. Methods TDM was performed in 180 pediatric patients treated with quetiapine. Psychopathological changes were assessed by the Clinical Global Impression - Improvement scale (CGI-I). Adverse drug reactions (ADRs) were assessed by using a short form of the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale. Results A weak positive linear relationship between daily dose (mean 349.9±248.9 mg/day) and serum concentration of quetiapine (rs=0.496, p<0.001) was found (mean age 15.6±1.9 years, 45.6% male, 31.1% monotherapy), but no relationship between serum concentration and clinical outcome was found. Dose variation accounted for only 12.5% (rs2=0.125) of the variability of serum concentrations. No effects by gender, age, body weight, smoking habits, and co-medication were found. The majority of patients with psychotic (67.8%) and mood disorders (74.5%) showed a serum concentration below the suggested lower limit (100 ng/mL) of the TR for adults. Discussion There are several limitations of this study because of the naturalistic design, and our results should therefore be interpreted with caution. Notwithstanding, our data suggest that the lower limit of the TR for quetiapine is lower than the limit in adult patients.