Exploring the Role of Probiotics and Antioxidants in Potentiating the Efficacy of Citalopram Hydrobromide for Depression Therapy: A Preclinical Study in Swiss Albino Mice Model

Background and objective: Depression is a leading cause of disability worldwide, characterized by mood disturbances and neurobiological alterations. The gut–brain axis and oxidative stress have emerged as critical factors in its pathophysiology. Probiotics, through microbiome modulation, and vitamin C, via antioxidant effects, have shown potential to improve depressive symptoms. Citalopram hydrobromide, a selective serotonin reuptake inhibitor, is widely used but has limitations, including delayed therapeutic onset and partial remission. This study aimed to investigate whether adjunctive administration of probiotics and vitamin C could enhance the antidepressant efficacy of citalopram hydrobromide in a stress-induced murine model of depression. Materials and methods: Adult Swiss albino mice (n=12) were randomized into four groups: vehicle control, stress control, standard (citalopram hydrobromide 10 mg/kg), and test (citalopram hydrobromide + probiotics + vitamin C). Stress was induced using deprivation and cold-water swim protocols over four weeks. Antidepressant activity was evaluated through the forced swim test, tail suspension test, and locomotor activity using an actophotometer. Data were analyzed using analysis of variance (ANOVA) with Tukey’s post hoc test. Results: The stress protocol significantly increased immobility and reduced locomotor activity compared to controls (p<0.0001). Citalopram hydrobromide reduced immobility in both forced swim test and tail suspension test, confirming antidepressant activity. The test group (citalopram hydrobromide + probiotics + vitamin C) showed significantly greater reductions in immobility (p<0.05–0.001) and enhanced locomotor activity compared to citalopram hydrobromide alone. These findings suggest synergistic effects via modulation of serotonergic pathways, antioxidant mechanisms, and gut–brain interactions. Conclusion: Adjunctive supplementation with probiotics and vitamin C potentiates the antidepressant efficacy of citalopram hydrobromide in a murine depression model. This multimodal strategy may represent a promising therapeutic approach for major depressive disorder, warranting further mechanistic and clinical investigation.