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

Authors Sychev D, Zastrozhin MS, Smirnov V, Grishina E, Savchenko L, Bryun E

Received 12 April 2016

Accepted for publication 17 June 2016

Published 14 September 2016 Volume 2016:9 Pages 89—95

DOI https://doi.org/10.2147/PGPM.S110385

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth


Dmitry Alekseevich Sychev,1 Mikhail Sergeevich Zastrozhin,1–3 Valery Valerieevich Smirnov,4 Elena Anatolievna Grishina,1 Ludmila Mikhailovna Savchenko,1 Evgeny Alekseevich Bryun1,2

1Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation, 2Department of Public Health, Moscow Research and Practical Centre for Narcology, 3Peoples’ Friendship University of Russia, 4National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia


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: haloperidol, biotransformation, CYP2D6, side effects, alcohol addiction

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