Georgios Schoretsanitis1,2, Benedikt Stegmann3, Christoph Hiemke4, Gerhard Gründer5, Koen R J Schruers6, Sebastian Walther7, Sarah E Lammertz5, Ekkehard Haen3, Michael Paulzen5. 1. Department of Psychiatry, Psychotherapy and Psychosomatics and JARA-Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. gschoretsani@ukaachen.de. 2. University Hospital of Psychiatry, Bern, Switzerland. gschoretsani@ukaachen.de. 3. Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany. 4. Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany. 5. Department of Psychiatry, Psychotherapy and Psychosomatics and JARA-Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. 6. Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands. 7. University Hospital of Psychiatry, Bern, Switzerland.
Abstract
PURPOSE: The aim of the study was to investigate a correlation between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety (AM) (RIS + 9-OH-RIS), and adverse drug reactions (ADRs) in a naturalistic sample. METHODS: Plasma concentrations of RIS, 9-OH-RIS, and AM in patients out of a therapeutic drug monitoring (TDM) database complaining ADRs were categorized according to the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 97) and compared to patients without ADRs (n = 398). RESULTS: Patients in the ADR group received a significantly lower daily dosage of risperidone (trimmed mean 3.64 mg/day) than patients without ADRs (4.40 mg/day). No differences were found for active moiety plasma concentrations between the groups (p = 0.454). Differences were detected only in the case of dose-adjusted plasma concentration values (concentration-by-dose, C/D) for 9-OH-RIS, being higher in patients reporting ADRs (4.78 ng/mL/mg) than in patients without ADRs (4.3 ng/mL/mg) (p = 0.037 for Mann-Whitney U test). Note that differences for non-adjusted 9-OH-RIS plasma levels between groups failed to reach significance (p = 0.697). CONCLUSIONS: Our findings are consistent with previous data supporting a prominent role of 9-hydroxyrisperidone, but not of risperidone with regard to ADRs. When studying the various subgroups of reported ADRs separately, the size of these subsamples offers some plausible limitations by reducing the power of the analysis.
PURPOSE: The aim of the study was to investigate a correlation between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety (AM) (RIS + 9-OH-RIS), and adverse drug reactions (ADRs) in a naturalistic sample. METHODS: Plasma concentrations of RIS, 9-OH-RIS, and AM in patients out of a therapeutic drug monitoring (TDM) database complaining ADRs were categorized according to the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 97) and compared to patients without ADRs (n = 398). RESULTS:Patients in the ADR group received a significantly lower daily dosage of risperidone (trimmed mean 3.64 mg/day) than patients without ADRs (4.40 mg/day). No differences were found for active moiety plasma concentrations between the groups (p = 0.454). Differences were detected only in the case of dose-adjusted plasma concentration values (concentration-by-dose, C/D) for 9-OH-RIS, being higher in patients reporting ADRs (4.78 ng/mL/mg) than in patients without ADRs (4.3 ng/mL/mg) (p = 0.037 for Mann-Whitney U test). Note that differences for non-adjusted 9-OH-RIS plasma levels between groups failed to reach significance (p = 0.697). CONCLUSIONS: Our findings are consistent with previous data supporting a prominent role of 9-hydroxyrisperidone, but not of risperidone with regard to ADRs. When studying the various subgroups of reported ADRs separately, the size of these subsamples offers some plausible limitations by reducing the power of the analysis.
Entities:
Keywords:
Antipsychotics; Drug metabolism; Pharmacokinetics; Psychopharmacology; Schizophrenia
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