Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep 14:9:89-95.
doi: 10.2147/PGPM.S110385. eCollection 2016.

The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction

Dmitry Alekseevich Sychev  1 , Mikhail Sergeevich Zastrozhin  2 , Valery Valerieevich Smirnov  3 , Elena Anatolievna Grishina  1 , Ludmila Mikhailovna Savchenko  1 , Evgeny Alekseevich Bryun  4
Affiliations

The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction

Dmitry Alekseevich Sychev et al. Pharmgenomics Pers Med. .

Abstract

Background: Today, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in metabolism of haloperidol. In our previous investigation, we found a medium correlation between the efficacy and safety of haloperidol and the activity of CYP3A4 in patients with alcohol abuse.

Objective: The aim of this study was to evaluate the correlation between the activity of CYP2D6 and the efficacy and safety of haloperidol in patients with diagnosed alcohol abuse.

Methods: The study involved 70 men (average age: 40.83±9.92 years) with alcohol addiction. A series of psychometric scales were used in the research. The activity of CYP2D6 was evaluated by high-performance liquid chromatography with mass spectrometry using the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline to pinoline. Genotyping of CYP2D6 (1846G>A) was performed using real-time polymerase chain reaction.

Results: According to results of correlation analysis, statistically significant values of Spearman correlation coefficient (rs) between the activity of CYP2D6 and the difference of points in psychometric scale were obtained in patients receiving haloperidol in injection form (Sheehan Clinical Anxiety Rating Scale =-0.721 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.692 [P<0.001]) and in those receiving haloperidol in tablet form (Covi Anxiety Scale =-0.851 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.797 [P<0.001]).

Conclusion: This study demonstrated the correlations between the activity of CYP2D6 isozyme and the efficacy and safety of haloperidol in patients with alcohol addiction.

Keywords: CYP2D6; alcohol addiction; biotransformation; haloperidol; side effects.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Relationship between activity of CYP2D6 and difference in scores on UKU (A) and SoPA (B) scales in patients receiving haloperidol in injection form. Abbreviations: UKU, Udvald for Kliniske Undersogelser Side Effect Rating Scale; SoPA, Scale of Pathological Addiction; 6-HO-THBC, 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline.
Figure 2
Figure 2
Relationship between activity of CYP2D6 and difference in scores on UKU (A) and SoPA (B) scales in patients receiving haloperidol in tablet form. Abbreviations: UKU, Udvald for Kliniske Undersogelser Side Effect Rating Scale; SoPA, Scale of Pathological Addiction; 6-HO-THBC, 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline.
See this image and copyright information in PMC

References

    1. National Institute for Health and Care Excellence [webpage on the Internet] Acute Alcohol Withdrawal. National Institute for Health and Care Excellence; 2015. [Accessed July 27, 2016]. Available from: http://pathways.nice.org.uk/pathways/alcohol-use-disorders.
    1. Stewart S, Swain S, NICE. Royal College of Physicians London Assessment and management of alcohol dependence and withdrawal in the acute hospital. Clin Med (Lond) 2012;12(3):266–271. - PMC - PubMed
    1. NHS [webpage on the Internet] Guidelines for the Management of Alcohol Issues in the Acute General Hospital Setting. 2006. [Accessed July 27, 2016]. Available from: http://www.alcohollearningcentre.org.uk/_library/17__Doncaster_Guideline....
    1. Ivanec NN. Cancer therapy. Med News Agency. 2008:531–580.
    1. Fang J, Baker GB, Silverstone PH, Coutts RT. Involvement of CYP3A4 and CYP2D6 in the metabolism of haloperidol. Cell Mol Neurobiol. 1997;17(2):227–233. - PMC - PubMed

LinkOut - more resources