Introduction. Anxiety-depressive disorders are among the most common psychiatric disorders in the group of borderline conditions, and antidepressants are widely used for their treatment. Around the world, there is an active development of new drugs with thymoanaleptic activity, as well as in-depth study and comparison of the efficacy and safety of existing drugs. Due to this, the approach to psychopharmacotherapy of anxiety-depressive disorders and the very structure of prescribing antidepressants are constantly changing. Thus, the analysis of the structure of prescribing antidepressants, as well as the identification and justification of the changes that this structure inevitably undergoes over time, becomes extremely relevant. Purpose of the study. Conduct a pharmacoepidemiological analysis of the structure of prescribing antidepressants to patients with anxiety-depressive disorders of the neurotic register (F 06.41 — Organic anxiety disorder due to cerebrovascular disease, F 41.0 — Panic disorder (episodic paroxysmal anxiety), F 41.2 — Mixed anxiety and depressive disorder and F 45 — Somatoform disorders according to ICD-10) in two comparable groups of patients treated in the Department of Crisis States of the Clinic of Hematology and Occupational Pathology of the SSMU in 2010–2012 and 2019–2021 respectively. Materials and methods. The volume of antidepressant prescriptions was assessed, taking into account dosages and treatment regimens, using the «Defined Daily Doses» technique in each of the study groups. Differences in the structure of prescribing antidepressants in the study groups were identified and analyzed, as well as the causes and prerequisites for their occurrence were investigated. Results. The conducted comparative pharmacoepidemiological study revealed discrepancies in the structure of antidepressant prescriptions in the 2010–2012 groups. and 2019–2021 Maprotiline was in second place in terms of prevalence in the 2010–2012 group, while in the 2019–2020 group never been appointed. By the end of the decade, the frequency of prescribing clomipramine significantly decreased, which in the 2010–2012 group ranked third in terms of appointments. When comparing groups of 2010–2012 and 2019–2021 it was found that in the first case, the volume of clomipramine prescriptions was almost 6 times higher. There is a trend towards an increase in the volume of prescriptions for almost all drugs of the SSRI group, both individually and for this group as a whole. The structure of prescriptions is significantly influenced by such factors as an in-depth study of the main and side effects of drugs, accessibility for patients and the volume of supplies of individual drugs to the territory of the Russian Federation. Conclusion. Modern pharmacoepidemiological studies make it possible to study in depth the advantages and disadvantages of each specific antidepressant, so that in each clinical case it is possible to choose the most suitable drug or combination thereof. It is necessary to continue and increase the scale of such studies, maintaining their independence from the financing of pharmaceutical companies, as well as to expand the local market for psychopharmacotherapeutic agents so that its limitations do not reduce the effectiveness of the therapy on a large scale.