Rewiring Mood: Precision Psychobiotics as Adjunct or Stand-Alone Therapy in Depression Using Insights from 19 Randomized Controlled Trials in Adults.

Depression is a leading contributor to global disability, with a large proportion of patients showing inadequate responses to conventional antidepressants. Probiotic bacteria with psychotropic potential seem to be an emerging treatment option, either alone or in conjunction with depression symptom management. To critically review the Randomized Clinical Trials (RCTs) whose primary focus was to evaluate the efficacy of probiotics/psychobiotics to ameliorate depression status, quantified via validated psychometric tools. A comprehensive literature search of the PubMed and Scopus databases (January 2014-January 2025) was conducted to identify RCTs with the primary aim of improving depression status in adults taking probiotics in comparison to those taking a well-defined placebo. Nineteen RCTs met the inclusion criteria, with all demonstrating a significant amelioration of depression status after probiotic/psychobiotic treatment, taken either as a stand-alone treatment [ = 5] or as an adjunctive treatment to antidepressant therapy [ = 10]. However, only in 14 studies was a significant improvement achieved at the end of treatment over a placebo, which also showed an improvement against the baseline. In total, 7 out of 10 studies with probiotics as an add-on therapy and 7 out of the 9 with probiotics, either as a monotherapy or with a different percentage also taking antidepressants, exhibited a significant amelioration of depression status against placebo treatment. Probiotics, particularly multi-strain preparations and certain well-characterized single strains, seem to be noticeably beneficial in alleviating depressive symptoms in adults. However, there is an urgent need for large-scale randomized clinical trials with well-defined specific psychobiotic strains in order to confirm the most effective strains.