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

  • Faculty of Human Medicine
  • Universidad de San Martín de Porres
  • International Research Unit in Molecular Pharmacology and Genomic Medicine (UNIPHARMOGEM)
  • Universidad San Ignacio de Loyola
  • General Studies
  • Universidad Nacional Mayor de San Marcos
  • Faculty of Pharmacy and Biochemistry
  • Universidad Nacional de Trujillo
  • Graduate School
  • Human Medicine
  • Universidad Continental

Research output: Contribution to journal › Review article › peer-review

Abstract

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.

Original languageEnglish
Article numbere173102
JournalPharmacia
Volume72
DOIs
StatePublished - 20 Nov 2025

Keywords

  • adverse drug reactions
  • biomarkers
  • pharmacogenes
  • poor metabolizers
  • schizophrenia
  • second-generation antipsychotics

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