A Prospective Study to Evaluate the Effect of CYP2D6 Polymorphism on Plasma level of Risperidone and its Metabolite in North Indian Patients with Schizophrenia

BACKGROUND: Risperidone is one of commonly utilized antipsychotic in clinical practice. Various metabolizing enzymes effect the plasma levels of risperidone and its active metabolite and thus its clinical efficacy. So, we attempted to evaluate the relationship between CYP2D6*10 (rs1065852) and CYP2D6*4 (rs3892097) gene polymorphism and the plasma concentration of risperidone and its metabolite in patients with schizophrenia. METHODOLOGY: It was a 12-week prospective study carried out in patients diagnosed with schizophrenia. The dose of risperidone was increased weekly by 1 mg and rating of psychopathology was done using Positive and Negative Syndrome Scale (PANSS). Quantification of plasma level of risperidone and 9-hydroxyrisperidone was carried out at week 6 and 12 of treatment. The *4 and *10 alleles of CYP2D6 were genotyped and their effect on metabolism of risperidone was assessed. RESULTS: The number of CYP2D6*4 alleles affected the plasma levels of risperidone, 9-hydroxyrisperidone at 6 weeks of treatment but not at 12 weeks. On the other hand, the number of mutated alleles for CYP2D6*10 influenced the dose corrected plasma concentration of risperidone and active moiety at 12 weeks of treatment. The ratio of plasma concentration of risperidone and 9-hydroxyrisperidone was more than one in all study participants, thus, suggesting that they were poor metabolizers of risperidone. CONCLUSION: The polymorphism of CYP2D6*10 affects the steady state plasma concentration of risperidone in Indian patients with schizophrenia.