Objective. A comparative evaluation of the efficacy and safety of a multimodal antidepressant therapy with venlafaxine plus cerebrolysin and monotherapy with the same antidepressant for the treatment of depression in elderly patients in a psychiatric hospital. Material and methods. Two groups of patients (20 patients in each group), aged 60 years and older (60 to 79 years), were studied. The groups were matched for demographic and clinical (severity of depressive episode) characteristics. Patients of the first group were treated with venlafaxine in dose 75-150 mg twice a day. Patients of the second group received additionally 20 intravenous infusions of cerebrolysin (20.0 ml in 100 ml isotonic sodium chloride solution). Results. Therapeutic effect of antidepressant therapy (56 days) was characterized by a good balanced profile in relation to symptoms of depression, anxiety and apathy in both groups. However, the use of multimodal therapy allowed to get the more rapid response and more pronounced therapeutic effect compared to monotherapy with the same antidepressant, as well as to reduce adverse events. Conclusion. The results obtained allow to recommend multimodal antidepressant therapy with venlafaxine and cerebrolysin for using in hospital practice to achieve a more rapid therapeutic response, reduce the risk of adverse effects of antidepressants and shorten a period of hospitalization.