Genomic Insights Into Risperidone Treatment Outcomes in Children and Adolescents: Experience From a Psychiatric Hospital Serving Rural Youth

Risperidone is a commonly used antipsychotic for treating psychiatric illness in children and adolescents. There is a large variability in risperidone response and discontinuation rates remain high. Pharmacogenomics offers the opportunity to improve risperidone outcomes, yet studies in pediatric populations are limited. We conducted a genome-wide association study (GWAS) to investigate genetic predictors of risperidone response in pediatric patients (n = 161) who received inpatient care at a pediatric hospital in a rural setting. Clinical, demographic, and treatment outcomes data, collected retrospectively, were incorporated into predictive models. While 41.0% of patients discontinued risperidone, patients remained on risperidone longer than other antipsychotics, with the exception of quetiapine. Female patients discontinued more quickly, as did patients in the acute program compared to residential. We identified nine genetic variants associated with risperidone outcomes: duration of risperidone treatment and frequency of risperidone discontinuation (rs10270303, intronic variant, PTPRN2), maximum risperidone dose (rs6014649, intergenic variant between CBLN4 and MC3R; rs56261530, synonymous variant, SHD), time to readmission (rs35722167, intergenic variant between UGT2A3 and UGT2B7; rs62382382, intronic variant, SGCD; rs62466698, intergenic variant between BET1 and GNG11; rs1152938, intronic variant, CPM), and duration of hospital stay (rs117426990, 3'-UTR variant, TMX3; rs5956073, intergenic variant between DOCK11 and LINC01285). Our study is the first GWAS of risperidone response in pediatric populations, which provides insights into the biological complexity of risperidone response, as well as moving toward precision antipsychotic treatment. Our study demonstrates the high value of conducting research in a community-based setting and highlights the need to expand research studies beyond academic medical centers.