Therapeutic drug monitoring in children and adolescents with schizophrenia-spectrum, affective, behavioural, tic and other psychiatric disorders treated with aripiprazole: results of the TDM-VIGIL pharmacovigilance study.

Autor: Riegger J; Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany., Egberts KM; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany. Egberts_K@ukw.de., Clement HW; Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany., Schneider-Momm K; Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany., Taurines R; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany., Fekete S; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany., Wewetzer C; Clinic for Child and Adolescent Psychiatry Holweide, Kliniken der Stadt Köln GmbH, Children's Hospital Amsterdamer Straße, Cologne, Germany.; KIRINUS Tagesklinik Nymphenburg, Munic, Germany., Karwautz A; Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria., Correll CU; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.; Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.; Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA., Plener PL; Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria.; Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital Ulm, Ulm, Germany., Malzahn U; Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany., Heuschmann P; Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany.; Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Wuerzburg, Germany.; Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany., Unterecker S; Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany., Scherf-Clavel M; Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany., Rock H; Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany., Antony G; Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany., Briegel W; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany.; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Leopoldina Hospital, Schweinfurt, Germany., Banaschewski T; Department of Child and Adolescent Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany., Hellenschmidt T; Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic medicine, Vivantes Clinic Berlin Neukölln, Berlin, Germany., Kaess M; Clinic for Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany.; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland., Kölch M; Department of Child and Adolescent Psychiatry and Psychotherapy, Brandenburg Medical School Brandenburg, Neuruppin, Germany.; Department of Child and Adolescent Psychiatry, Neurology, Psychosomatics, and Psychotherapy, University Medical Center Rostock, Rostock, Germany., Renner T; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Psychiatry and Psychotherapy Tuebingen, Center of Mental Health Tuebingen, Tuebingen, Germany., Rexroth C; Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Regensburg at the Regensburg District Hospital, Medbo, Regensburg, KU, Germany., Schulte-Körne G; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany., Walitza S; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland.; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland.; Neuroscience Center Zurich, University of Zurich and ETH, Zürich, Switzerland., Gerlach M; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany., Romanos M; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany., Fleischhaker C; Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany. Christian.fleischhaker@uniklinik-freiburg.de.
Jazyk: angličtina
Zdroj: Journal of neural transmission (Vienna, Austria : 1996) [J Neural Transm (Vienna)] 2024 Nov 02. Date of Electronic Publication: 2024 Nov 02.
DOI: 10.1007/s00702-024-02819-6
Abstrakt: Aripiprazole is approved for various severe mental disorders in adults and adolescents. However, off-label prescribing is common, especially in children and adolescents (youth) in whom aripiprazole therapeutic serum level reference ranges are lacking for any disorders. The aim of the study was to evaluate the relationship between aripiprazole dose and serum concentrations and provide further knowledge on the use of aripiprazole in order to improve drug safety and effectiveness in the treatment of minors. The clinical course of youth treated with aripiprazole in the multicentre pharmacovigilance study TDM-VIGIL was systematically followed and serum concentrations measured. Sex, age, weight and comedications were analysed to identify possible effect modifiers. A preliminary therapeutic reference range was estimated for youth with schizophrenia-spectrum disorders, affective disorders and behavioural/emotional/tic disorders coded as treatment responders based on a Clinical-Global Impressions-Improvement (CGI-I) score of much or very much improved. In 93 youth (mean age = 15.2 ± 2.6, range = 7.4-18.2 years, females = 53%, CGI-Severity = 4.4 ± 1.1, responders = 64%), a positive, moderate correlation between the weight-normalized daily dose (WNDD) and aripiprazole serum concentration (=0.791, p < 0.0001) was found. The WNDD and co-medications that interact with CYP2D6 and CYP3A4 affected aripiprazole serum levels, explaining 64% of the variance. In patients within the preliminary therapeutic ranges determined by interquartile ranges (IQRs), slightly better outcomes and fewer adverse drug reactions were found versus patients within preliminary therapeutic ranges determined by the mean ± SD. The preliminary reference range for paediatric patients with schizophrenia-spectrum disorders calculated by the IQR showed an identical lower threshold (100-230 ng/ml) compared to adult schizophrenia-spectrum disorders patients (100-350 ng/ml). The preliminary therapeutic ranges for patients with affective disorders was: 60-160 ng/ml and for patients with behavioural/tic disorders 60-140 ng/ml. The therapeutic reference ranges for aripiprazole in youth estimated via the 25th and 75th IQRs may result in more clinically relevant therapeutic windows. Further studies need to confirm these results, especially in patients with affective and behavioural/tic disorder diagnoses.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: