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01-08-2016 | Psychiatry and Preclinical Psychiatric Studies - Original Article

Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice

Authors: Christopher Wohkittel, Manfred Gerlach, Regina Taurines, Christoph Wewetzer, Stefan Unterecker, Rainer Burger, Diana Schreck, Claudia Mehler-Wex, Marcel Romanos, Karin Egberts

Published in: Journal of Neural Transmission | Issue 8/2016

Abstract

Information on dose- and concentration-related clinical effects of clozapine treatment in children and adolescents is scarce. This study aimed to examine the relationship between dose, serum concentration, and clinical outcome as well as the influencing factors thereof in paediatric patients treated with clozapine. Data from a routine Therapeutic Drug Monitoring (TDM) service between 2004 and 2014 were studied in 68 patients, aged 11–18 years. Severity of illness, therapeutic effectiveness and adverse drug reactions (ADRs) were assessed by standardized means. A relationship between the daily dose (mean 319 mg, 4.9 mg/kg) and serum concentration (mean 387 ng/ml) of clozapine was found with the variation in dose explaining 30 % of the variability in clozapine serum concentrations. Also gender contributed to the variability, however, no influence of age or concomitant medications was detected. Furthermore, a significant association was found between clozapine serum concentration and the occurrence of ADRs. Patients without ADRs had a lower mean serum concentration than those with mild (261.4 vs 407.3 ng/ml, P = 0.018) and moderate ADRs (261.4 vs 416.3 ng/ml, P = 0.028). As clozapine was estimated to be effective in lower blood concentrations, guidance on a possibly lower therapeutic range of clozapine serum levels in paediatric patients is provided. With ADRs increasing under higher concentrations, TDM is strongly recommended in paediatric clozapine therapy for individualized dosing. Dose adjustment in females also might be reasonable according to gender-related differences in serum concentrations. However, regarding the limitations of this study results should be validated in larger studies with more standardized designs.

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Title: Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice
Authors: Christopher Wohkittel
Manfred Gerlach
Regina Taurines
Christoph Wewetzer
Stefan Unterecker
Rainer Burger
Diana Schreck
Claudia Mehler-Wex
Marcel Romanos
Karin Egberts
Publication date: 01-08-2016
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 8/2016
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-016-1573-y

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