Introduction: Although pharmacogenetic tests provide the information on a genotype and the predicted phenotype, these tests themselves do not provide the interpretation of data for a physician. There are currently approximately two dozen pharmacogenomic clinical decision support systems used in psychiatry. Implementation of clinical decision support systems capable of forming recommendations on drug and dose selection according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task may allow increasing the efficacy of therapy and decreasing the risk of undesirable side effects. Materials and methods: The study included 51 male patients (21 in the main group and 30 in the control group) with alcohol withdrawal syndrome. To evaluate the efficacy and safety of therapy, several international psychometric scales and rating scales to measure side effects were used. Genotyping was performed using real‐time polymerase chain reaction with allele‐specific hybridization. Pharmacogenetic test results were interpreted using free software PGX2 ( www.pgx2.com ). Results: Statistically significant differences between the scores derived from all psychometric scales were revealed. For instance, the total score on CIWA‐Ar scale by day 3 was 13.5 [11.2; 16.0] for the main group and 18.0 [17.0; 22.0] ( p < 0.001) for the control group; by day 5, it was 6.5 [4.2; 8.0] for the main group and 15.0 [14.0; 16.0] ( p < 0.001) for the control group. The UKU side effect rating scale (UKU) also revealed a statistically significant difference. The total score on UKU scale by day 3 was 6.0 [5.0; 7.0] for the main group and 7.0 [6.0; 8.0] ( p < 0.001) for the control group; by day 5, this difference grew significantly: 5.5 [3.0; 9.0] for the main group and 14.0 [12.0; 19.0] ( p < 0.001) for the control group. The groups were representative (there was no difference between the scores at the inclusion of patients). Conclusion: Pharmacogenetic‐guided personalization of drug dose in patients with alcohol withdrawal syndrome can reduce the risk of undesirable side effects and pharmacoresistance. It allows recommending the use of pharmacogenomic clinical decision support systems for optimizing drug dosage.

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.