Review: Influence of the CYP450 Genetic Variation on the Treatment of Psychotic Disorders

Second-generation antipsychotic metabolism is mainly carried out by the CYP450 superfamily, which is highly polymorphic. Therefore, knowing the influence of the different known CYP450 polymorphisms on antipsychotic plasmatic levels and, consequently, the biological effect could contribute to a deeper knowledge of interindividual antipsychotic treatment variability, prompting possible solutions. Considering this, this state of the art review aimed to summarize the current knowledge about the influence of the diverse characterized phenotypes on the metabolism of the most used second-generation antipsychotics. Forty studies describing different single nucleotide polymorphisms (SNPs) associated with the genes CYP1A2, CYP2D6, CYP3A4, CYP3A5, and ABCB1 and their influence on pharmacokinetics of olanzapine, clozapine, aripiprazole, risperidone, and quetiapine. Most of the authors concluded that although significant differences in the pharmacokinetic parameters between the different phenotypes could be observed, more thorough studies describing pharmacokinetic interactions and environmental conditions, among other variables, are needed to fully comprehend these pharmacogenetic interactions.

Automated summary

Current research has summarized the influence of different CYP450 gene polymorphisms on the metabolism of second-generation antipsychotic drugs, particularly olanzapine, clozapine, aripiprazole, risperidone, and quetiapine. Although significant differences in pharmacokinetic parameters between different phenotypes have been observed, more comprehensive studies describing pharmacokinetic interactions and environmental conditions among other variables are needed to fully understand these pharmacogenetic interactions.