Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice
| Autor: | C. Mehler-Wex, Manfred Gerlach, M Romanos, R Taurines, Karin Egberts, Stefan Unterecker, Christoph Wewetzer, R. Burger, Christopher Wohkittel, Diana Schreck |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Neurology Adolescent 03 medical and health sciences 0302 clinical medicine Pharmacotherapy Therapeutic index Internal medicine Severity of illness medicine Humans 0501 psychology and cognitive sciences Longitudinal Studies Child Clozapine Biological Psychiatry Retrospective Studies medicine.diagnostic_test Dose-Response Relationship Drug business.industry Mental Disorders 05 social sciences Retrospective cohort study 030227 psychiatry Psychiatry and Mental health Treatment Outcome Therapeutic drug monitoring Anesthesia Concomitant Female Neurology (clinical) Drug Monitoring business 050104 developmental & child psychology medicine.drug Antipsychotic Agents |
| Zdroj: | Journal of neural transmission (Vienna, Austria : 1996). 123(8) |
| ISSN: | 1435-1463 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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