The impact of CYP2D6 variation on risperidone-related side effects in a Nigerian pediatric population
Risperidone is an atypical antipsychotic drug indicated for the treatment of schizophrenia, bipolar disorder, and autism-related irritability in youth. Side effects are common, often resulting in therapeutic discontinuation or switching to another antipsychotic drug. Risperidone is primarily metabolized by hepatic enzyme cytochrome P450 2D6 (CYP2D6) into its active metabolite, 9-hydroxyrisperidone (which is also prescribed as paliperidone). The side effect profiles of risperidone and paliperidone are different, with more hyperprolactinemia occurring in the paliperidone-treated patients. Herein, we propose a prospective observational study of the influence of CYP2D6 on response and tolerability in risperidone-treated patients at the Child and Adolescent Mental Health Service Centre (CAMHSC), Federal Neuro-Psychiatric Hospital (FNPH) Yaba, Lagos, Nigeria.
Aim 1: Characterize CYP2D6 genetic variation in a Nigerian pediatric population. Hypothesis: Frequencies of CYP2D6 star alleles and the population-wide metabolizer status profile will be unique to this population compared to the predominantly European populations that currently dominate the literature.
Aim 2: Determine if CYP2D6 phenotypes are associated with risperidone-related side effects in this Nigerian pediatric population. Hypothesis: Poor metabolizers are at an increased risk for side effects from risperidone because of their inability to convert risperidone into its active metabolite, and ultrarapid metabolizers are at increased risk of hyperprolactinemia due to increased concentrations of the active metabolite.
Aim 3: Determine the influence of CYP2D6 variation on the pharmacokinetics of risperidone in pediatric patients. Hypothesis: Loss-of-function (no function *40) and decreased function (*17, *29, *41) CYP2D6 variants will be associated with higher risperidone:9-hydroxyrisperidone ratio.