Relationship of CYP3A4*1B Single Nucleotide Polymorphism to the Efficiency and Safety Profiles of Haloperidol in Patients Enduring Acute Alcoholic Hallucinosis

A A Parkhomenko; M S Zastrozhin; VYu Skryabin; A E Petukhov; S A Pozdniakov; V A Ivanchenko; I A Zaytsev; I V Bure; P O Bochkov; K A Akmalova; V V Smirnov; E A Bryun; D A Sychev

Relationship of CYP3A41B* Single Nucleotide Polymorphism to the Efficiency and Safety Profiles of Haloperidol in Patients Enduring Acute Alcoholic Hallucinosis

Psychopharmacol Bull. 2023 Dec 4;53(4):8-14.

Authors

A A Parkhomenko¹, M S Zastrozhin², VYu Skryabin³, A E Petukhov⁴, S A Pozdniakov⁵, V A Ivanchenko⁶, I A Zaytsev⁷, I V Bure⁸, P O Bochkov⁹, K A Akmalova¹⁰, V V Smirnov¹¹, E A Bryun¹², D A Sychev¹³

Affiliations

¹ Parkhomenko, postgraduate student at the Department of Addiction Medicine, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia.
² Zastrozhin, PhD, MD, Associate professor of addiction psychiatry department.
³ Skryabin, PhD, MD, head of clinical department; Associate professor of addiction psychiatry department.
⁴ Petukhov, PhD, MD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring; associate professor of pharmaceutical and toxicological chemistry, Moscow, Russia.
⁵ Pozdniakov, researcher of the laboratory of genetics and fundamental studies.
⁶ Ivanchenko, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.
⁷ Zaytsev, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.
⁸ Bure, Senior Researcher, Predictive and Prognostic Biomarkers Department, Research Institute of Molecular and Personalized Medicine.
⁹ Bochkov, Senior Researcher, Predictive and Prognostic Biomarkers Department, Research Institute of Molecular and Personalized Medicine.
¹⁰ Akmalova, Researcher at the Department of Predictive and Prognostic Biomarkers of the Research Institute of Molecular and Personalized Medicine.
¹¹ Smirnov, Dr. Pharm. Sc, Head of the scientific and production complex FGBU "SSC Institute of Immunology" FMBA of Russia, National Research Center-Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russian Federation.
¹² Bryun, PhD, MD, professor, president, head of addiction psychiatry department.
¹³ Sychev, corresponding member of the Academy of Sciences of Russia, MD, PhD, professor, rector, head of clinical pharmacology and therapy department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.

PMID: 38076668
PMCID: PMC10698852 (available on 2024-12-04)

Abstract

To date, haloperidol has been widely used to treat patients with acute alcoholic hallucinosis. There is strong evidence that haloperidol therapy is commonly associated with adverse drug reactions (ADRs). The 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) is known to affect the metabolism rates of haloperidol; hence it correlates with both therapy efficacy and safety parameters.

Objective: The study objective was to investigate the effect of 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) on the efficacy and safety profiles of haloperidol in patients with acute alcoholic hallucinosis.

Methods: This study enrolled 100 male patients suffering from acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile of haloperidol was assessed using the PANSS (Positive and Negative Syndrome Scale) validated psychometric scale. The safety profile of therapy was assessed with the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR).

Results: There were no statistically significant results for the efficacy rates (dynamics of the PANSS score: AA genotype -14.00 [-16.00; -12.00], AG genotype -13.00 [-14.00; -10.50], p = 0.306). Similarly, there was no statistically significant difference in the safety profiles (dynamics of the UKU score: AA genotype - 9.00 [7.00; 13.00], AG genotype - 8.50 [7.25; 10.50], p = 0.620; dynamics of the SAS score: AA genotype -12.00 [10.00; 16.75], AG genotype - 10.00 [10.00; 12.25], p = 0.321).

Conclusion: The study demonstrated that the 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) in patients with acute alcoholic hallucinosis does not affect the efficacy and safety rates of haloperidol therapy.

Keywords: CYP3A4; acute alcoholic hallucinosis; adverse drug reactions; haloperidol; personalized medicine; pharmacogenetics.

MeSH terms

Adult
Antipsychotic Agents* / adverse effects
Antipsychotic Agents* / therapeutic use
Cytochrome P-450 CYP3A / genetics
Genotype
Haloperidol* / adverse effects
Haloperidol* / therapeutic use
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide

Substances

Antipsychotic Agents
CYP3A4 protein, human
Cytochrome P-450 CYP3A
Haloperidol