Omics biomarkers of antipsychotic efficacy and safety: focus on lurasidone

Abstract

Introduction. Lurasidone is an atypical antipsychotic with high affinity for 5-HT₂A, 5-HT₇, and DRD2 receptors; however, its use is limited by interindividual pharmacokinetic variability and dose-dependent adverse effects. Multi-omics approaches offer opportunities for personalized dosing. Objective. To systematically review evidence on genomic, transcriptomic, and epigenomic biomarkers associated with lurasidone efficacy and safety. Methods. A literature search was conducted in PubMed, Scopus, and RSCI (2010–2026) using keywords: lurasidone, pharmacogenomics, CYP3A4, HTR1A, microRNA, therapeutic drug monitoring. Of 187 initially identified publications, 83 sources were selected after screening. Results. The rs6295 polymorphism of the HTR1A gene is associated with lurasidone efficacy in European schizophrenia patients. CYP3A4 is the main metabolizing enzyme: CYP3A4*1G (rs2242480) significantly affects clearance (CL/F: C/C — 330 L/h, T/T — 441 L/h); CYP3A4*15 requires dose adjustment up to 240 mg/day in carriers. In hepatic impairment, dose reduction to 20–40 mg/day is recommended. Transcriptomic studies identified 1907 differentially expressed genes, including modulation of PER1 and BMAL1, as well as neurotransmitter imbalance. MicroRNAs (miR-181b, miR-21, miR-122) are promising biomarkers for response prediction and CYP activity monitoring. Lurasidone monotherapy efficacy in bipolar II depression does not exceed 41.3 %. Conclusion. The most clinically relevant markers are CYP3A4 (rs2242480, CYP3A4*15) and HTR1A (rs6295) polymorphisms, as well as microRNAs. Prospective studies are required to validate multi-omics panels in clinical practice.