Background: depressions in elderly and senile patients often occur against the background of cerebral changes of vascular and atrophic origin and are combined with impaired cognitive functions. It is known that a decrease in the production of neurotrophic factors is one of the leading mechanisms in the pathogenesis of depression. Previously, the effectiveness of combined therapy with antidepressants and drugs with neuroprotective properties has been shown, but a differentiated approach to the appointment of neuroprotective adjuvants needs substantiation. The aim of the study was to carry out comparative evaluation of the effectiveness of two augmentation methods of antidepressant therapy with the inclusion of different neuroprotectors (actovegin or cerebrolysin) in the treatment of depression in the elderly. Patients and methods: the study included 2 groups of patients with a depressive episode of mild and moderate severity, comparable in terms of basic demographic and clinical parameters. Patients of the 1st group received antidepressants in combination with actovegin for a month. Patients of the 2nd group received cerebrolysin simultaneously with antidepressants. The effectiveness of therapy was assessed on the HAMD-17 and HARS scales; the level of cognitive functioning of patients was assessed using the MMSE scale. Results: the effectiveness of both used types of complex antidepressant therapy was demonstrated: both with the inclusion of actovegin and with the inclusion of cerebrolysin. In patients of both groups, against the background of a reduction in depressive symptoms, a significant (p < 0.01) improvement in cognitive functioning (according to the MMSE scale) was noticed by the end of therapy (without statistically significant differences between the groups). The inclusion of actovegin in the antidepressant therapy regimen for elderly patients proved to be effective regardless of the type of depression, but especially in the reduction of anxiety symptoms. Administration of cerebrolysin to depressed patients was more effective in anergic, asthenic, apathetic and adynamic depressions. Conclusion: augmentation of antidepressant therapy with actovegin and cerebrolysin should be considered effective and recommended for use in a psychogeriatric hospital.