Can J Physiol Pharmacol. 2025 Oct 24. doi: 10.1139/cjpp-2025-0174. Online ahead of print.
ABSTRACT
Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS), offering unparalleled efficacy but accompanied by significant interindividual variability in response and risk of severe adverse effects. Pharmacogenomics (PGx), the study of how genetic variations influence drug response, has transformed treatment for other medications like warfarin but remains underutilized in clozapine prescribing. This review synthesizes current evidence on the potential of PGx to enhance clozapine treatment by improving the prediction of therapeutic response, metabolism, and adverse drug reactions. Key genetic markers, such as variants in serotonin receptor genes (e.g., HTR2A, HTR3A), metabolism-related enzymes (CYP1A2), and immunerelated genes (HLA-DQB1, HLA-B*59:01), show promise in guiding personalized clozapine prescribing. However, economic, educational, and systemic challenges, particularly in Canada, hinder broader implementation. PGx testing in psychiatry is available but lacks standardization in cost, accessibility, and test panels. Additionally, PGx research remains Eurocentric, with limited data on Indigenous and diverse populations. In Canada, initiatives like Go-PGx reflect growing national interest, but mental health applications remain minimal. Bridging research with practice through inclusive research, clinician education, artificial intelligence and machine learning, and cost-effectiveness analyses may help unlock PGx’s full potential for over 200,000 Canadians living with schizophrenia.
PMID:41135088 | DOI:10.1139/cjpp-2025-0174
