Effectiveness and Safety of Probiotic as Adjunctive Therapy in Depression Disorder

Depression is a major global health problem, and current treatments are often limited by delayed therapeutic effects, side effects, and incomplete response, particularly in moderate to severe cases. Increasing evidence highlights the role of the gut–brain axis in mood regulation, where gut microbiota influence immune, inflammatory, and neurochemical pathways. In this context, probiotics have emerged as a promising adjunctive approach, as they may modulate gut microbiota, regulate immune responses, and influence neuroactive compounds, potentially reducing depressive symptom severity. However, further well designed research are needed to confirm their efficacy and safety in depression management. A systematic review was conducted by including valid and relevant articles from PubMed, ScienceDirect, and Springerlink, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 553 relevant articles published between 2018 to February 2026 were screened, resulting in 10 included studies. Data regarding baseline sample characteristics, as well as the effectiveness and safety profiles of probiotic in depression disorder, were collected and reported descriptively. A total of 10 studies involving depression patients were included in this systematic review. The synthesis results showed that probiotic supplementation shows potential as an adjunctive therapy for major depressive disorder, with several randomized controlled trials reporting greater reductions in depressive symptom scores and anxiety levels compared to placebo when combined with standard antidepressant treatment. Although findings were not entirely consistent across trials due to variations in strains, dosage, duration, and participant characteristics, meta analytic evidence suggests that adjunctive probiotic therapy provides statistically significant clinical benefits with a favorable safety profile, as adverse effects were generally mild and comparable to placebo. Overall, while probiotics cannot yet be recommended as standalone treatment, current evidence supports their promise as a complementary intervention in depression management. Probiotics show promise as a safe adjunctive treatment for depression, particularly in individuals with major depressive disorder who have not achieved optimal response to antidepressants alone.