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

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 (r_s) 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

Acknowledgments

The authors are grateful to KB Mirzaev, KA Rizhikova, JA Avdeeva and NE Snalina at the research center of Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation for assistance in the genotyping of patients. This work was supported by the Russian Science Foundation. The project 16-15-00227 “Fundamental research and exploratory research in priority areas of research”. The abstract of this paper was presented at the First International Conference on “Personalized psychiatry: modern possibilities of genetics in psychiatry” (Russia, Moscow, 2015) as a poster presentation with interim findings. The poster’s abstract was published in The Bulletin of Russian State Medical University.¹²

Disclosure

The authors report no conflicts of interest in this work.