Topicality. Currently, there is a need to find approaches to early treatment of depressive symptoms in patients with chronic non-communicable diseases, which would allow to begin management of symptoms at the beginning of their occurrence. A promising candidate for the role of such therapy may be the complex Deprilium^®, which contains S-adenosyl-L-methionine (SAMe), L-methylfolate and methylcobalamin. The aim: to evaluate the effectiveness of Deprilium^® in relieving subclinical symptoms of depression in patients with chronic non-communicable diseases. Materials and methods. Study design: a double-blind randomized controlled trial with parallel groups. On the basis of the Department of Medical Psychology, Psychosomatic Medicine and Psychotherapy of the O.O. Bogomolets National Medical University (monocentric study) in compliance with ethical and deontological norms in accordance with the principles set out in the Declaration of Helsinki, involved 140 patients. The Hamilton Depression Scale (HAM-D) was used to assess subclinical symptoms. The somatic symptoms scale (SSS-8) and the O.S. Chaban quality of life scale (QOLS) were used to obtain additional information about the patient’s condition. Patients were randomized to block randomization in the Deprilium^® study group and the placebo control group. Results. After 60 days (T2), there was a statistically significant difference in all clinical parameters between the study group and the control group. The median value of the HAM-D scale differed between groups by 6 points, significantly (p<0.000) lower results were observed in the study group, which participants took the Deprilium^® complex. When comparing the indicators of the study group on day 1 (T1) and 60 days (T2) of participation in the study, statistically significant changes (p<0.000) were observed in all three indicators. Conclusion. Our results confirm the available evidence for the effectiveness of SAMe as a therapy for depression and complement their evidence of the effectiveness of the Deprilium^® complex containing SAMe and L-methylfolate with methylcobalamin, which together cause pharmacological and clinical synergism for synergism, in subclinical depressive manifestations in patients with common chronic non-communicable diseases. In addition, it was found that taking the Deprilium^® complex for 2 months does not contain an increased risk to patient health and significant side effects. Further studies of the effectiveness of Deprilium^® in patients with chronic non-communicable diseases are needed.