Objective. To develop a personalized approach to the appointment of a complex antidepressant therapy in combination with drugs of neuroprotective and neurotrophic action in depressed elderly patients based on the selection of predictors of low therapeutic response (LTR). Material and methods. The study included 152 hospitalized patients, aged 60 years and older, with moderate and mild depression (ICD-10) who received monotherapy (44 people) with antidepressants of the new generation and complex therapy (108 people) with the same antidepressants in combination with neuroprotective drugs. In the monotherapy group, correlations between treatment efficacy (change in average total HAMD-17 scores) and a set of parameters, including socio-demographic data, results of psychopathological, somatic, standardized assessment and neuroimaging (CT) of the brain were analyzed. The validity of the established correlations as predictors of LTR was estimated based on a comparison of their frequency among the responders (≥50% reduction) and non-responders (<50% reduction). Comparison of the efficacy of therapy in groups of patients with mono — and complex therapy was carried out depending on the presence or absence of predictors of LTR. Results. LTR predictors are living alone, complaints about memory loss and signs of pronounced diffuse lesions of the subcortical white matter of the brain, which are significantly more frequently observed in non-responders (p<0.05). The increase in the number of predictors (2 and more) correlates with a significant decrease in therapeutic efficacy (p<0.001). Patients with complex in structure and protracted depressions tend to decrease in efficiency, and in most of them (more than 87% of cases) LTR predictors are detected. In patients with LTR predictors, the complex therapy is significantly more effective than monotherapy, allowing in all cases to achieve 50% reduction of depressive symptoms by the 4th week of treatment. Conclusion. Personalized indications for the appointment of complex antidepressant therapy in combination with neuroprotective drugs in depressed elderly patients are formulated.