[Personalized Pharmacotherapy with Sertraline in Patients with Anxiety-Depressive Disorder Based on Omics Biomarkers]

Sertraline, a selective serotonin reuptake inhibitor, is widely used as a first-line drug for anxiety and depressive disorders. The clinical efficacy and adverse reactions observed with antidepressants are closely related to the concentration of this drug in the patient's blood, but the vast majority of antidepressants demonstrate significant pharmacokinetic variability, leading to pronounced interindividual differences in the steady-state concentration of the drug in the blood and its efficacy even with the same dosing regimen. In this regard, it has become obvious that genetic markers alone are not enough to obtain the most complete profile of the efficacy and safety of a drug; a combination of genotyping methods with omics biomarkers is necessary. As a result of examination of patients, residents of the Republic of Bashkortostan, that had been diagnosed with mixed anxiety-depressive disorder (F41.2), it was found that polymorphic variants rs16947 (CYP2D6*2), rs389209 (CYP2D6*4), and rs1065852 (CYP2D6*10) of the CYP2D6 gene do not have a significant effect on the activity of CYP2D6. Genetically determined variations in the activity of the CYP2D6 isoenzyme lead to differences in the metabolism of sertraline and its active metabolite N-desmethylsertraline in different patients, which causes variability in their concentrations in the blood plasma. A statistically significant increase in the plasma concentrations of sertraline and N-desmethylsertraline was found in patients carrying the slow allelic variants rs3892097, rs1065852, and rs16947 of the CYP2D6 gene. A statistically significant moderate inverse correlation was found between the dose and the metabolic ratio C6-HO-THBC/CP. The results obtained are preliminary, which makes it necessary to continue this study with an expanded sample size.