Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone

R Taurines; S Fekete; A Preuss-Wiedenhoff; A Warnke; C Wewetzer; P Plener; R Burger; M Gerlach; M Romanos; K M Egberts

doi:10.1007/s00702-022-02485-6

Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone

J Neural Transm (Vienna). 2022 Jun;129(5-6):689-701. doi: 10.1007/s00702-022-02485-6. Epub 2022 Mar 18.

Authors

R Taurines¹, S Fekete¹, A Preuss-Wiedenhoff¹, A Warnke¹, C Wewetzer², P Plener^{3

4}, R Burger⁵, M Gerlach¹, M Romanos¹, K M Egberts⁶

Affiliations

¹ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Margarete-Hoeppel-Platz 1, 97080, Wuerzburg, Germany.
² Clinic for Child and Adolescent Psychiatry and Psychotherapy, Clinics of the City Cologne GmbH, Cologne, Germany.
³ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Ulm, Ulm, Germany.
⁴ Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
⁵ Department of Psychiatry, Psychosomatics and Psychotherapy, Laboratory for Therapeutic Drug Monitoring, Centre for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany.
⁶ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Margarete-Hoeppel-Platz 1, 97080, Wuerzburg, Germany. [email protected].

Abstract

Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose-concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20-60 ng/ml) is applicable for minors. In the 64 patients (aged 11-18 years) included, a positive correlation between daily dose and the active moiety (RIS_am) concentration was found (r_s = 0.49, p = 0.001) with variation in dose explaining 24% (r_s² = 0.240) of the variability in serum concentrations. While the RIS_am concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RISam concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RIS_am was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.

Keywords: Children; Pharmacovigilance; Risperidone; Schizophrenia; Serum concentration; Therapeutic drug monitoring.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Antipsychotic Agents* / adverse effects
Basal Ganglia Diseases* / chemically induced
Child
Drug Monitoring
Humans
Paliperidone Palmitate / therapeutic use
Psychotic Disorders* / drug therapy
Risperidone / therapeutic use
Schizophrenia* / drug therapy

Substances

Antipsychotic Agents
Risperidone
Paliperidone Palmitate