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Risperidone-treated Children and Adolescents with Behavioral Disorders: Do Drug Dose and Patients’ Gender and Age Relate to Drug and Metabolite Plasma Levels?

Published online by Cambridge University Press:  23 March 2020

D. Piacentino ,
M. Grözinger ,
A. Saria ,
F. Scolati ,
D. Arcangeli ,
P. Girardi ,
M. Pompili  and
A. Conca
D. Piacentino
Affiliation:
NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University of Rome, School of Medicine and Psychology, Sant’Andrea Hospital, Rome, Italy Department of Psychiatry, San Maurizio Hospital, Sanitary Agency of South Tyrol, Bolzano, Italy
M. Grözinger
Affiliation:
Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Uniklinik RWTH Aachen, Aachen, Germaany
A. Saria
Affiliation:
Experimental Psychiatry Unit, Medizinische Universität Innsbruck, Innsbruck, Austria
F. Scolati
Affiliation:
Handicap and Psychological Distress Service, Social Services Agency of South Tyrol, Bolzano, Italy
D. Arcangeli
Affiliation:
Provincial Service of Developmental Psychiatry and Psychotherapy, Sanitary Agency of South Tyrol, Bolzano, Italy
P. Girardi
Affiliation:
NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University of Rome, School of Medicine and Psychology, Sant’Andrea Hospital, Rome, Italy
M. Pompili
Affiliation:
NESMOS Department (Neurosciences, Mental Health, and Sensory Organs), Sapienza University of Rome, School of Medicine and Psychology, Sant’Andrea Hospital, Rome, Italy
A. Conca
Affiliation:
Department of Psychiatry, San Maurizio Hospital, Sanitary Agency of South Tyrol, Bolzano, Italy Provincial Service of Developmental Psychiatry and Psychotherapy, Sanitary Agency of South Tyrol, Bolzano, Italy

Abstract

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Introduction

Behavioral disorders, such as conduct disorder, influence choice of treatment and its outcome. Less is known about other variables that may have an influence.

Objectives/Aims

We aimed to measure the parent drug and metabolite plasma levels in risperidone-treated children and adolescents with behavioral disorders and investigate the role of drug dose and patients’ gender and age.

Methods

We recruited 115 children/adolescents with DSM-5 behavioral disorders (females = 24; age range: 5–18 years) at the Departments of Psychiatry of the Hospitals of Bolzano, Italy, and Innsbruck, Austria. We measured risperidone and its metabolite 9-hydroxyrisperidone plasma levels and the parent drug-to-metabolite ratio in the plasma of all patients by using LC-MS/MS. A subsample of 15 patients had their risperidone doses measured daily. We compared risperidone and 9-hydroxyrisperidone plasma levels, as well as risperidone/9-hydroxyrisperidone ratio, in males vs. females and in younger (≤ 14 years) vs. older (15–18 years) patients by using Mann-Whitney U test. We fitted linear models for the variables “age” and “daily risperidone dose” by using log-transformation, regression analysis and applying the R2 statistic.

Results

Females had significantly higher median 9-hydroxyrisperidone plasma levels (P = 0.000). Younger patients had a slightly lower median risperidone/9-hydroxyrisperidone ratio (P = 0.052). At the regression analysis, daily risperidone doses and metabolite, rather than parent drug–plasma levels were correlated (R2 = 0.35).

Conclusions

Gender is significantly associated with plasma levels, with females being slower metabolizers than males. Concerning age, younger patients seem to be rapid metabolizers, possibly due to a higher activity of CYP2D6. R2 suggests a clear-cut elimination of the metabolite.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
Oral communications: Rehabilitation and psychoeducation and schizophrenia and other psychotic disorders
Information
European Psychiatry , Volume 41 , Issue S1: Abstract of the 25th European Congress of Psychiatry , April 2017 , pp. S104
Copyright
Copyright © European Psychiatric Association 2017
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