Variants of the dopamine D-2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents

C CALARGE; V ELLINGROD; L ACION; D MILLER; J MOLINE; M TANSEY; J SCHLECHTE

PHARMACOGENETICS AND GENOMICS

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2009

1744-6872

ObjectiveTo investigate the association between hyperprolactinemia and variants of the dopamine D2 receptor (DRD2) gene in children and adolescents in long-term treatment with risperidone.MethodsMedically healthy 7?17-year-old patients chronically treated with risperidone but receiving no other antipsychotics were selected for a cross-sectional evaluation. Four DRD2 variants were genotyped and prolactin concentration was measured. Medication history was obtained from the medical record. The effect of the TaqIA variants of the DRD2 on the risk of risperidone-induced hyperprolactinemia was the primary outcome measure.ResultsHyperprolactinemia was present in 50% of 107 patients (87% males) treated with risperidone for an average of 2.9 years. Age, stage of sexual development, and the dose of risperidone independently predicted a higher prolactin concentration, whereas the dose of psychostimulants was negatively correlated with it. However, these four predictors became nonsignificant when risperidone serum concentration was entered into the model. Adverse events potentially related to hyperprolactinemia were more common in participants with elevated prolactin concentration in girls (45%) compared with boys (10%). After controlling for risperidone concentration and the dose of psychostimulants, the TaqIA A1 and the A-241G alleles were associated with higher prolactin concentration, whereas the -141C Ins/Del AQ1and C957T variants had no significant effect. In addition, adverse events potentially related to hyperprolactinemia were four times more common in TaqIA A1 allele carriers.ConclusionProlactin concentration is closely related to central DRD2 blockade, as reflected by risperidone serum concentration. Furthermore, the TaqIA and A-241G variants of the DRD2 gene could be useful in predicting the emergence of hyperprolactinemia and its potential adverse events.