title: Pharmacokinetic patterns of risperidone-associated adverse drug reactions.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics and JARA-Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. gschoretsani@ukaachen.de.|University Hospital of Psychiatry, Bern, Switzerland. gschoretsani@ukaachen.de.
authors.forename: Georgios
authors.identifier: http://orcid.org/0000-0002-3851-4117
authors.initials: G
authors.lastname: Schoretsanitis
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Stegmann
authors.affiliation: Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics and JARA-Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
authors.forename: Koen R J
authors.initials: KR
authors.lastname: Schruers
authors.affiliation: University Hospital of Psychiatry, Bern, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Walther
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics and JARA-Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lammertz
authors.affiliation: Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Haen
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics and JARA-Translational Brain Medicine, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulzen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate / Q000097:blood*; D018967:Risperidone / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: Antipsychotics; Drug metabolism; Pharmacokinetics; Psychopharmacology; Schizophrenia