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


METHODS
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.


CONCLUSIONS
In patients with ASD treated with risperidone, a CYP2D6 phenotype may be associated with response to treatment and development of ADRs.
Clinical Pharmacology Unit, Assaf Harofeh Medical Center, Zerifin, Israel.
Ilan
I
Youngster
Ditza A
DA
Zachor
Lidia V
LV
Gabis
Adina
A
Bar-Chaim
Patricia
P
Benveniste-Levkovitz
Malka
M
Britzi
Stefan
S
Soback
Tomer
T
Ziv-Baran
Matitiahu
M
Berkovitch
D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D010641:Phenotype; D010865:Pilot Projects; D018967:Risperidone / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone