Background Bromodihydrochlorophenylbenzodiazepine (Phenazepam®) is used in the therapy of anxiety disorders in patients with alcohol dependence. However, Phenazepam therapy often turns out to be ineffective, and some patients develop dose-related adverse drug reactions (ADR): severe sedation, dizziness, headache, dyspepsia, falling, etc. That ensures the effectiveness of this category of patients. Despite the popularity of Phenazepam® as an anxiolytic drug, there is currently no accurate data on its biotransformation, as well as the effect of polymorphism of a gene on the efficacy and safety of bromodihydrochlorophenylbenzodiazepine in patients. The aim of our study was to study the effect of the polymorphism of the CYP2C19 gene on the efficacy and safety index of Phenazepam® for patients with anxiety disorders, using algorithms for optimizing the therapy of Phenazepam® to reduce the risk of pharmacological resistance and increase the effectiveness of therapy. Methods The study was conducted on 86 Russian patients suffering from alcohol dependence. Patients with trauma anxiety disorders received bromdihydrochlorphenylbenzodiazepine in tablets at a dose of 4.0 [2.0; 6.0] mg per day for 5 days. Genotyping was carried out by the method of polymer chain reaction in real time with allele-specific hybridization. Efficiency and safety assessment was carried out using psychometric scales and scales of Hospital Anxiety and Depression Scale (HADS) severity scores. Results Based on the results of the study, statistically significant differences in the number of scores on the scale of HADS severity of CYP2C19 CT on the third day of therapy were the following: (CC) 10.00 [9.00; 11.00], (CT) 14.00 [13.00; 16.00], (TT) 18.00 [17.00; 19.00], p=0.00, and also on the fifth day: (CC) 6.00 [5.00; 7.00], (CT) 17.50 [16.25; 19.75], (TT) 22.50 [20.00; 24.00], p=0.00. ADRs in patients with different genotypes for this polymorphic marker did not differ. Conclusions Thus, it has been shown that the polymorphism of the CYP2C19 gene may influence the effectiveness indices of Phenazepam therapy in patients with anxiety disorders comorbid with alcohol dependence. This should be taken into account in the appointment of this drug in this way in order to increase effectiveness of therapy and improve the quality of life.
Aim: Conduct a meta-analysis of promising studies that compare the pharmacogenetic method of dosing antidepressants and the traditional one. Materials and methods: The search for publications was carried out in the eLibrary systems (www.elibrary.ru), PubMed (www.pubmed.ru), Google scholar, Scopus, Web of Science until 2019. In addition, articles were selected from the literature lists of the found publications. The meta-analysis includes studies that compared the clinical outcomes between the FGT group (experimental) and the control group. The selection of the dose of antidepressants to patients of the experimental group was carried out taking into account the results of genetic testing. These data were not taken into account in the control group. The selected studies were conducted in groups of adult patients who scored on the HDRS scale ≥ 19 points, who were shown to take antidepressants. Results: In 5 articles studied by us, the number of patients who responded to therapy, who were in remission, as well as reducing the number of side effects in the experimental and control groups were compared. The analysis of the data showed the presence of statistically significant differences in the experimental and control groups. In the groups with the pharmacogenetic approach, a large number of patients with remission and responses to therapy were observed, but no effect on the development of the number of side effects was revealed. Conclusion: A meta-analysis of prospective foreign studies has shown the advantage of using a pharmacogenetic approach in prescribing therapy.
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