Pharmacogenes associated with adverse reactions induced by second-generation antipsychotic drugs: A systematic review

Pharmacogenes are specific genes that determine how an individual will respond to medication. Some of these genes have been linked to adverse reactions caused by second-generation antipsychotics. A literature search was conducted using relevant terms across the PubMed, CTG Studies, and Scopus databases. The included articles examined pharmacogenes associated with adverse reactions induced by second-generation antipsychotics. The articles were published between 2015 and 2025. A total of 12 observational studies were included. The review protocol is registered in PROSPERO (CRD420251035803). The studies demonstrated an association of CYP1A2 with adverse reactions induced by aripiprazole ( p < 0.035), clozapine ( p = 0.009, p = 0.042, and p = 0.046), and olanzapine ( p < 0.05). CYP2C19 was associated with clozapine-induced metabolic syndrome ( p < 0.01). CYP3A4 was associated with clozapine-induced hyperglycemia (χ² = 0.1), and CYP3A5 was associated with quetiapine ( p < 0.007). CYP2D6 was linked to adverse reactions induced by clozapine ( p = 0.039), olanzapine ( p = 0.047), risperidone ( p = 0.021 and p = 0.02), and quetiapine ( p = 0.003). This review shows that certain allelic variants of pharmacogenes are associated with adverse reactions to second-generation antipsychotics. This finding applies to patients with impaired metabolism. We recommend conducting longitudinal multicenter studies before promoting allelic variants of pharmacogenes as predictive biomarkers.