Antipsychotic drug-aripiprazole against schizophrenia, its therapeutic and metabolic effects associated with gene polymorphisms

Pharmacol Rep. 2023 Feb;75(1):19-31. doi: 10.1007/s43440-022-00440-6. Epub 2022 Dec 16.

Abstract

Second-generation antipsychotics are widely used for the treatment of schizophrenia. Aripiprazole (ARI) is classified as a third-generation antipsychotic drug with a high affinity for dopamine and serotonin receptors. It is considered a dopamine-system stabilizer without severe side effects. In some patients the response to ARI treatment is inadequate and they require an effective augmentation strategy. It has been found that the response to the drug and the risk of adverse metabolic effects can be related to gene polymorphisms. A reduced dose is recommended for CYP2D6 poor metabolizers; moreover, it is postulated that other polymorphisms including CYP3A4, CYP3A5, ABCB1, DRD2, and 5-HTRs genes influence the therapeutic effect of ARI. ARI can increase the levels of prolactin, C-peptide, insulin, and/or cholesterol possibly due to specific genetic variants. It seems that a pharmacogenetic approach can help predict drug response and improve the clinical management of patients with schizophrenia.

Keywords: Antipsychotics; Aripiprazole; CYP450 system; Genetic polymorphism; Pharmacogenetics; Schizophrenia; Treatment response.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents* / adverse effects
  • Aripiprazole / adverse effects
  • Dopamine
  • Drug-Related Side Effects and Adverse Reactions*
  • Humans
  • Polymorphism, Genetic
  • Schizophrenia* / drug therapy
  • Schizophrenia* / genetics

Substances

  • Antipsychotic Agents
  • Aripiprazole
  • Dopamine