Effects of Probiotics As Adjunctive Therapy to Fluoxetine on Depression Severity and Serum Brain-Derived Neurotrophic Factor, Cortisol, and Adrenocorticotropic Hormone in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial Publisher



Elahinejad V¹ ; Khorasanian AS^{1, 2} ; Tehranidoost M³ ; Khosravidarani K⁴ ; Mirsepasi Z³ ; Effatpanah M⁵ ; Askarirabori R⁶ ; Tajadod S¹ ; Jazayeri S^{1, 7} Show Affiliations
Source: Food Science and Nutrition Published:2025

Abstract

Probiotics may improve mood, but their role as adjunctive therapy for major depressive disorder (MDD) is not well understood. This study examines the effects of probiotics on depression severity, brain-derived neurotrophic factor (BDNF), adrenocorticotropic hormone (ACTH), and cortisol levels in MDD patients. Fifty medication-free MDD patients were randomized to receive probiotics with fluoxetine (n = 25) or placebo with fluoxetine (n = 25) for 8 weeks. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-24), and fasting blood samples were collected at baseline and study conclusion. Forty-four patients completed the trial. The probiotic group showed a significant reduction in depression severity compared with the placebo group (p = 0.001). No significant differences were observed in serum cortisol (p = 0.46) and ACTH levels (p = 0.44). Plasma BDNF levels increased slightly in the probiotic group but were not statistically significant. Probiotic supplementation with fluoxetine significantly reduces depression severity in MDD patients. © 2025 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.