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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

Genetic Testing is Superior Over Endogenous Pharmacometabolomic Markers to Predict Safety of Haloperidol in Patients with Alcohol-induced Psychotic Disorder

Author(s): Valentin Skryabin*, Mikhail Zastrozhin, Alexandra Parkhomenko, Volker M. Lauschke, Valery Smirnov, Aleksey Petukhov, Elena Pankratenko, Sergei Pozdnyakov, Sergei Koporov, Natalia Denisenko, Kristina Akmalova, Evgeny Bryun and Dmitry Sychev

Volume 23, Issue 13, 2022

Published on: 09 January, 2023

Page: [1067 - 1071] Pages: 5

DOI: 10.2174/1389200224666221228112643

Price: $65


Background: Previous studies have shown that haloperidol biotransformation is mainly metabolized by CYP2D6. The CYP2D6 gene is highly polymorphic, contributing to inter-individual differences in enzymatic activity, and may impact haloperidol biotransformation rates, resulting in variable drug efficacy and safety profiles.

Objective: The study aimed to investigate the correlation of the CYPD6 activity with haloperidol's efficacy and safety rates in patients with alcohol-induced psychotic disorders.

Methods: One hundred male patients received 5-10 mg/day haloperidol by injections for 5 days. The efficacy and safety assessments were performed using PANSS, UKU, and SAS-validated psychometric scales.

Results: No relationship between haloperidol efficacy or safety and the experimental endogenous pharmacometabolomic marker for CYP2D6 activity, urinary 6-НО-ТНВС/pinoline ratio was identified. In contrast, we found a statistically significant association between haloperidol adverse events and the most common CYP2D6 loss-of-function allele CYP2D6*4 (p<0.001).

Conclusion: Evaluation of the single polymorphism rs3892097 that defines CYP2D6*4 can predict the safety profile of haloperidol in patients with AIPD, whereas metabolic evaluation using an endogenous marker was not a suitable predictor. Furthermore, our results suggest haloperidol dose reductions could be considered in AIPD patients with at least one inactive CYP2D6 allele.

Keywords: CYP2D6, pharmacogenetics, personalized medicine, alcohol-induced psychotic disorder, alcoholic hallucinosis, haloperidol.

Graphical Abstract
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