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

Alvarado-Vera E.A.; Alvarado-Vera C.A.; Alvarado A.T.; Bartra M.S.; García J.A.; Bendezú M.R.; Palomino-Jhong J.J.; Chávez H.; Laos-Anchante D.; Melgar-Merino E.J.; Cuba-García P.A.; Yarasca-Carlos P.E.; Pariona-Llanos R.; Sagástegui-Guarniz W.; Maguiña Ignacio A.E.; Bolarte-Arteaga M. · Pharmacia (2025) · DOI: 10.3897/pharmacia.72.e173102

Resumen

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. Copyright Alvarado-Vera EA et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Instituciones: Universidad Nacional Mayor de San Marcos; Universidad Nacional de Trujillo; Universidad Nacional San Luis Gonzaga; Universidad de San Martín de Porres; Universidad San Ignacio de Loyola; Universidad Continental