Serum Concentration–Dose Relationship and Modulation Factors in Children and Adolescents Treated with Fluvoxamine

Regina Taurines; Gesa Kunkel; Stefanie Fekete; Jörg M. Fegert; Christoph Wewetzer; Christoph U. Correll; Kristian Holtkamp; Isabel Böge; Tobias Johann Renner; Hartmut Imgart; Maike Scherf-Clavel; Peter Heuschmann; Manfred Gerlach; Marcel Romanos; Karin Egberts

doi:10.3390/pharmaceutics16060772

Pharmaceutics (Jun 2024)

Serum Concentration–Dose Relationship and Modulation Factors in Children and Adolescents Treated with Fluvoxamine

Regina Taurines,
Gesa Kunkel,
Stefanie Fekete,
Jörg M. Fegert,
Christoph Wewetzer,
Christoph U. Correll,
Kristian Holtkamp,
Isabel Böge,
Tobias Johann Renner,
Hartmut Imgart,
Maike Scherf-Clavel,
Peter Heuschmann,
Manfred Gerlach,
Marcel Romanos,
Karin Egberts

Affiliations

Regina Taurines: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health, University Hospital of Wuerzburg, 97080 Wuerzburg, Germany
Gesa Kunkel: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health, University Hospital of Wuerzburg, 97080 Wuerzburg, Germany
Stefanie Fekete: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health, University Hospital of Wuerzburg, 97080 Wuerzburg, Germany
Jörg M. Fegert: Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Ulm, 89075 Ulm, Germany
Christoph Wewetzer: Clinics of the City Cologne GmbH, Clinic for Child and Adolescent Psychiatry and Psychotherapy, 51109 Cologne, Germany
Christoph U. Correll: Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
Kristian Holtkamp: DRK Fachklinik Bad Neuenahr, 53474 Bad Neuenahr-Ahrweiler, Germany
Isabel Böge: Department of Child and Adolescent Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, 8036 Graz, Austria
Tobias Johann Renner: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Psychiatry and Psychotherapy Tuebingen, Center of Mental Health, 72076 Tuebingen, Germany
Hartmut Imgart: Parkland-Clinic, Clinic for Psychosomatics and Psychotherapy, Academic Teaching Hospital for the University Gießen, 34537 Bad Wildungen, Germany
Maike Scherf-Clavel: Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
Peter Heuschmann: Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, 97080 Wuerzburg, Germany
Manfred Gerlach: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health, University Hospital of Wuerzburg, 97080 Wuerzburg, Germany
Marcel Romanos: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health, University Hospital of Wuerzburg, 97080 Wuerzburg, Germany
Karin Egberts: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Centre for Mental Health, University Hospital of Wuerzburg, 97080 Wuerzburg, Germany

DOI: https://doi.org/10.3390/pharmaceutics16060772
Journal volume & issue: Vol. 16, no. 6
p. 772

Abstract

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Introduction: Fluvoxamine is used in children and adolescents (‘youths’) for treating obsessive compulsive disorder (OCD) but also off-label for depressive and anxiety disorders. This study aimed to investigate the relationship between fluvoxamine dose and serum concentrations, independent correlates of fluvoxamine concentrations, and a preliminary therapeutic reference range (TRR) for youths with OCD and treatment response. Methods: Multicenter naturalistic data of a therapeutic drug monitoring service, as well as prospective data of the ‘TDM Vigil study’ (EudraCT 2013-004881-33), were analyzed. Patient and treatment characteristics were assessed by standardized measures, including Clinical Global Impressions—Severity (CGI-S) and —Change (CGI-I), with CGI-I of much or very much improved defining treatment response and adverse drug reactions using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. Multivariable regression analysis was used to evaluate the influence of sex, age, body weight, body mass index (BMI), and fluvoxamine dose on fluvoxamine serum concentrations. Results: The study included 70 youths (age = 6.7–19.6 years, OCD = 78%, mean fluvoxamine dose = 140.4 (range = 25–300) mg/d). A weak positive correlation between daily dose and steady-state trough serum concentrations was found (rs = 0.34, p = 0.004), with dose variation explaining 16.2% of serum concentration variability. Multivariable correlates explaining 25.3% of the variance of fluvoxamine concentrations included higher fluvoxamine dose and lower BMI. Considering responders with OCD, the estimated TRR for youths was 55–371 ng/mL, exceeding the TRR for adults with depression of 60–230 ng/mL. Discussion: These preliminary data contribute to the definition of a TRR in youth with OCD treated with fluvoxamine and identify higher BMI as a moderator of lower fluvoxamine concentrations.

Published in Pharmaceutics

ISSN: 1999-4923 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceutics/

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