CYP2D6 genotyping in paediatric patients with autism treated with risperidone: a preliminary cohort study.

Abstract

AIM:

To evaluate the association between cytochrome P450 2D6 (CYP2D6) phenotypes in paediatric patients with autistic spectrum disorders (ASD) treated with risperidone, adverse drug reactions (ADRs), and drug efficacy.

METHOD:

An observational cohort study of 40 children (34 males, six females; median age 7y range 3-18y) with autistic disorder, pervasive developmental disorder not otherwise specified, or Asperger syndrome diagnosed using the Autism Diagnostic Interview-Revised and treated with risperidone for at least 3 months. Charts were reviewed for demographic and clinical information, response to treatment was assessed by parents and the treating neurologist on a three-point scale, and information about ADRs was collected. Trough plasma levels of risperidone and its metabolites were determined and CYP2D6 genotyping was performed.

RESULTS:

Twenty-six patients responded to therapy and 11 patients exhibited ADRs. CYP2D6 genotyping showed two patients to be poor metabolizers, two ultra-rapid metabolizers, seven intermediate metabolizers, and 29 extensive metabolizers. Both ultra-rapid metabolizer patients were non-responders and had no ADRs. In contrast, both poor metabolizer patients were responders but experienced ADRs. No correlation was found between risperidone dosage and either risperidone or drug metabolite plasma levels. There was no difference in risperidone or metabolite plasma levels when comparing responders to non-responders, or when comparing patients with or without ADRs.

INTERPRETATION:

In patients with ASD treated with risperidone, a CYP2D6 phenotype may be associated with response to treatment and development of ADRs.

• Authors: Ilan Youngster, Ditza A Zachor, Lidia V Gabis, Adina Bar-Chaim, Patricia Benveniste-Levkovitz, Malka Britzi, Stefan Soback, Tomer Ziv-Baran, Matitiahu Berkovitch
• Journal: Developmental medicine and child neurology (Dev Med Child Neurol) Vol. 56 Issue 10 Pg. 990-4 (Oct 2014) ISSN: 1469-8749 [Electronic] England
• PMID: 24828442 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Mac Keith Press.

Chemical References

• Antipsychotic Agents
• Cytochrome P-450 CYP2D6
• Risperidone

Topics

• Adolescent
• Antipsychotic Agents (adverse effects, metabolism, pharmacology)
• Child
• Child Development Disorders, Pervasive (drug therapy, genetics, metabolism)
• Child, Preschool
• Cohort Studies
• Cytochrome P-450 CYP2D6 (genetics)
• Female
• Genotype
• Humans
• Male
• Pharmacogenetics (methods)
• Phenotype
• Pilot Projects
• Risperidone (adverse effects, metabolism, pharmacology)
• Treatment Outcome