AUTHOR=Vasiliu Octavian 

TITLE=The pharmacogenetics of the new-generation antipsychotics – A scoping review focused on patients with severe psychiatric disorders

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1124796

DOI=10.3389/fpsyt.2023.1124796

ISSN=1664-0640

ABSTRACT=Exploring the possible correlations between gene variations and the clinical effects of the new-generation antipsychotics is considered essential in the framework of personalized medicine. It is expected that pharmacogenetic data will be useful for increasing the treatment efficacy, tolerability, therapeutic adherence, functional recovery, and quality of life in patients with severe psychiatric disorders (SPD). A narrative scoping review investigated the available evidence about the pharmacokinetics, pharmacodynamics, and pharmacogenetics of five new-generation antipsychotics, i.e., cariprazine, brexpiprazole, aripiprazole, lumateperone, and pimavanserin. Based on the analysis of 25 primary and secondary sources and the review of these agents’ summaries of product characteristics, aripiprazole benefit from the most relevant data about the impact of gene variability on its pharmacokinetics and pharmacodynamics, with significant consequences on this antipsychotic’s efficacy and tolerability. The determination of the CYP2D6 metabolizer status is important when administering aripiprazole, both as monotherapy and associated with other drugs. Allelic variability in genes encoding D2, D3, 5HT2A, 5HT2C receptors, COMT, BDNF, and dopamine transporter DAT1 was also associated with different adverse events or variations in clinical efficacy. Brexpiprazole also benefits from specific recommendations regarding the CYP2D6 metabolizer status and the risks of associating this antipsychotic with strong/moderate CYP2D6 or CYP3A4 inhibitors. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) indications recommendations about cariprazine refer to possible pharmacokinetic interactions with strong CYP3A4 inhibitors or inducers. Pharmacogenetic data about cariprazine is sparse, and about lumateperone and pimavanserin are yet lacking. In conclusion, more studies are needed to detect the influence of gene variations on the pharmacokinetics and pharmacodynamics of new-generation antipsychotics. This type of research could increase the ability of clinicians to predict favorable responses to specific antipsychotics and to improve the tolerability of the treatment regimen in patients with SPD.