Gamze GÜRCAN, Berk ATALAY
Klinik Psikiyatri Dergisi - 2026;29(3):236-244
Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet its use is limited by interindividual variability in metabolism, efficacy, and adverse effects. This review examines the contribution of pharmacogenetics to these differences. A comprehensive literature review was conducted focusing on genetic determinants of clozapine pharmacokinetics, pharmacodynamics, treatment response, and adverse effects. Key cytochrome P450 enzymes, regulatory loci, and neurotransmitter receptor gene variants were evaluated. CYP1A2 polymorphisms and emerging loci such as NFIB significantly influence clozapine metabolism. Genetic variants in neurotransmitter receptor genes modulate efficacy and the risk of adverse effects, including weight gain and hematological abnormalities. Pharmacogenetic testing can complement therapeutic drug monitoring to optimize treatment outcomes. Pharmacogenetics enhances understanding of interindividual variability in clozapine response, but current evidence does not support routine genotype-based dosing. Personalized therapy integrating pharmacogenetic data, therapeutic drug monitoring, and clinical assessment remains the most promising approach. Further research is needed to implement these strategies in routine clinical practice.
