Farmacogenetics of response to risperidone in or not isolated use in the treatment of mental diseases in patients from 10 to 20 years old

Abstract

Risperidone is a drug commonly used in children and adolescents, but it presents some adverse effects such as gain of weight, metabolic syndrome, hormonal changes. Several genetic polymorphisms presenting potential susceptibility to the adverse effects of risperidone have being studied. This study will analyze if the risperidone adverse effects, upon isolated or non-isolated uses of the drug, would be associated with genetic polymorphisms in genes such as cytochrome P450, leptin and HTR2C, D2, MC4R and SCARB2 receptors. The casuistic will consist of approximately 100 subjects, aged between 10 and 20 years old upon risperidone use. It will be also included 100 young healthy adults under age 25 as a control group. Instruments such as K-SADS-P, CARS, AMSE score and WASI will be used to evaluate psychiatric status. In addition to clinical evaluation, insulin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, AST, ALT, free T4, TSH, prolactin and leptin will be dosed and those dosages will be repeated after 1, 2, 3, 6, 9, 12 and 24 months of treatment. The risperidone and 9-OH-risperidone serum levels will also be performed at 2, 6, 12 and 24 months of treatment. Polymorphisms in CYP2D6, HTR2C, DRD2, LEP, MC4R and SCARB2 genes will be evaluated in all subjects (case and control groups). In the control group, only the initial laboratory evaluation and the gene polymorphism analyses will be conducted. Descriptive analyses of all data will be conducted and repeated analysis of variance and association tests will be performed to compare the frequency of genotypes for case and control groups. For each SNP, the odds ratio (IC 95%) for the likelihood of association or non-association of a particular side effect will be estimated, with a significance level of 5%. (AU)