Effects Of CYP2C19*2 Polymorphisms on the Efficacy and Safety of Phenazepam in Patients with Anxiety Disorder and Comorbid Alcohol use Disorder

Abstract

Introduction: Phenazepam therapy can often be ineffective and some patients develop dose-related adverse drug reactions. Aim. The purpose of this research was to study the effect of the CYP2C19*2 (681G>A, rs4244285) in patients with anxiety disorders and alcohol dependence taking phenazepam therapy. Materials & methods: Patients (175 males, average age: 37.16 ± 7.84 years) received phenazepam in tablet form for 5 days. Genotyping was performed by real-time polymerase chain reaction. Results: The statistically significant differences in the UKU Side-Effect Rating Scale scores on the fifth day of therapy: (CYP2C19*1/*1) 2.00 [1.00; 2.00), (CYP2C19*1/*2) 7.00 (7.00; 7.00), (CYP2C19*2/*2) 9.00 (8.00; 9.00), p < 0.001. Conclusion: This study demonstrated the different efficacy and safety of phenazepam in patients with different genotypes of CYP2C19*2.

Keywords::

• alcohol addiction
• anxiety disorders
• benzodiazepines
• biotransformation
• bromodihydrochlorobenzodiazepine
• CYP2C19
• personalized medicine
• phenazepam

Acknowledgments

This work was supported by the project titled “Fundamental research and exploratory research in priority areas of research” of the Russian Science Foundation and by the President’s Grant of state support for the young scientists (project №MK-2460.2018.7).

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.