Impact of Nano-Selenium Supplementation Add-On Sertraline on Depressive Symptoms and Oxidative Stress in Patients With Major Depressive Disorder: A Triple-Blind Randomized Controlled Trial Publisher Pubmed



Noormohammadi M ; Etesam F ; Amini A ; Khosraviandehkordi P ; Mohamadzade M ; Shidfar F
Source: BioMetals Published:2025

Abstract

Major depressive disorder (MDD) is a prevalent psychiatric condition associated with increased oxidative stress, which may contribute to its pathophysiology. Elevated malondialdehyde (MDA) levels and reduced total antioxidant capacity (TAC) and glutathione peroxidase (GPX) activity have been observed in individuals with MDD. Nano-selenium, a novel formulation with enhanced bioavailability and antioxidant potency compared to conventional selenium, may help modulate these oxidative stress biomarkers. In this randomized, triple-blind, placebo-controlled trial, 50 adults newly diagnosed with MDD received either nano-selenium (55 µg/day) or placebo, both alongside sertraline (50 mg/day), over a 12-week period. A total of 42 participants (21 per group) completed the study. Depressive symptoms were measured using the Hamilton Depression Rating Scale (HDRS), and serum levels of GPX, TAC, and MDA were assessed at baseline and post-intervention. Compared to placebo, nano-selenium significantly reduced depressive symptoms (mean change: −5.09 ± 4.94; P < 0.001) and increased TAC (mean change: 0.03 ± 0.04 mmol/L; P = 0.003) and GPX levels (median change: 9.56 U/L; IQR: −7.86 to 30.31; P = 0.044). While MDA levels decreased significantly in both groups, between-group differences were not statistically significant. These findings suggest that nano-selenium may serve as a safe and effective adjunctive therapy for reducing depressive symptoms and improving antioxidant status in MDD. However, the short duration and modest sample size of this study limit generalizability. Larger, multicenter trials with extended follow-up are recommended to confirm and expand upon these results. This study was approved by the Research Ethics Committee of Iran University of Medical Sciences (IR.IUMS.REC.1402.206; June 13, 2023) and registered with the Iranian Registry of Clinical Trials (IRCT20091114002709N62; July 29, 2023). Written informed consent was obtained from all participants. © 2025 Elsevier B.V., All rights reserved.