Plasma risperidone-related measures in children and adolescents with oppositional defiant/conduct disorders
Daria Piacentino 1, 2*, Georgios D. Kotzalidis 3, Georgios Schoretsanitis 4, Michael Paulzen 5, 6, Ekkehard Haen 7, Alois Saria 8, Simone Cappelletti 9, Giancarlo Giupponi 2, Michael Grözinger 6, Andreas Conca 2
1NIAAA-NIDA, National Institutes of Health, 2Child, Adolescent, and Adult Psychiatry Unit, Department of Psychiatry, Central Hospital of Bolzano/Bozen, 3NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University of Rome, School of Medicine and Psychology, Sant'Andrea Hospital, Rome, Italy, 4The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA, 5Alexianer Hospital Aachen, Aachen, Germany, 6Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA – Translational Brain Medicine, 7Clinical Pharmacology, Department of Psychiatry and Psychotherapy and Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany, 8Department of General Psychiatry and Social Psychiatry, Medizinische Universität Innsbruck, Innsbruck, Austria, 9Anatomical, Histological, Forensic Medicine, and Orthopedic Sciences (SAIMLAL) Department, Sapienza University, Rome, Italy
Received: April 18, 2019; Revised: September 6, 2019; Accepted: September 6, 2019; Published online: September 6, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: Therapeutic drug monitoring helps clinicians in choosing the right drug and adjust its dose in specific patients. To this end, we aimed to assess time patterns of risperidone and its metabolite, 9-hydroxyrisperidone, in children and adolescents with oppositional defiant and/or conduct disorder. Methods: We measured plasma concentrations of risperidone and 9-hydroxyrisperidone, their sum (active moiety, AM) and ratio, as well as plasma concentrations corrected for daily dose (C/D), from 152 children/adolescents with the above-mentioned disorders. We used Student's t-test to compare females versus males, patients under versus over 16-year-old, patients with lower versus higher than the median body weight, and patients with lower versus higher than the median BMI. Two mixed-effects logistic regression models were fitted for risperidone/9-hydroxyrisperidone ratio and AM, respectively, by considering risperidone daily dose and patients’ demographic characteristics. Results: Females had higher 9-hydroxyrisperidone and AM plasma concentrations than males (p=0.004 and p=0.034). Younger patients had lower risperidone plasma concentration and risperidone/9-hydroxyrisperidone ratio (p=0.02 and p=0.021), but higher C/D 9-hydroxyrisperidone and AM than older patients (p=0.013 and p=0.043). Lower-weight patients had lower plasma risperidone and risperidone/9-hydroxyrisperidone ratio (p=0.014 and p=0.019), but higher C/D 9-hydroxyrisperidone concentration than heavier patients (p=0.03). All these results could be accounted for by daily dose. Patients with lower and higher BMI did not differ significantly. Regression analyses showed that only risperidone daily dose predicted risperidone/9-hydroxyrisperidone ratio, whereas risperidone daily dose, sex, and age predicted AM. Conclusions: Clinicians prescribing risperidone need to consider sex, age, and weight, but not BMI when adjusting daily doses.
Keywords: Oppositional defiant disorder, Conduct disorder, Youth, Risperidone, 9-Hydroxyrisperidone, Therapeutic Drug Monitoring


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