Updated Review and Meta-Analysis of Probiotics for the Treatment of Clinical Depression: Adjunctive vs. Stand-Alone Treatment

Abstract

Recent years have seen a rapid increase in the use of gut microbiota-targeting interventions, such as probiotics, for the treatment of psychiatric disorders. The objective of this update review was to evaluate all randomised controlled clinical trial evidence on the efficacy of probiotics for clinical depression. Cochrane guidelines for updated reviews were followed. By searching PubMed and Web of Science databases, we identified 546 new records since our previous review. A total of seven studies met selection criteria, capturing 404 people with depression. A random effects meta-analysis using treatment type (stand-alone vs. adjunctive) as subgroup was performed. The results demonstrated that probiotics are effective in reducing depressive symptoms when administered in addition to antidepressants (SMD = 0.83, 95%CI 0.49–1.17), however, they do not seem to offer significant benefits when used as stand-alone treatment (SMD = −0.02, 95%CI −0.34–0.30). Potential mechanisms of action may be via increases in brain-derived neurotrophic factor (BDNF) and decreases in C-reactive protein (CRP), although limited evidence is available at present. This review offers stronger evidence to support the clinical use of probiotics in depressed populations and provides an insight into the mode of administration more likely to yield antidepressant effects.

Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

“…Although most of pre-clinical studies and some clinical studies have demonstrated the efficacy of probiotics as a stand-alone treatment in depressive disorders, one of the recent meta-analyses of probiotic intervention in clinical depression concluded that probiotics are best used as an adjunct to antidepressants rather than as stand-alone treatment [25]. As an adjunct to antidepressants, probiotics could be utilized to tackle specific symptoms of depression.…”

“…The therapeutic potential of probiotics has been explored in a vast array of health conditions including type 2 diabetes, obesity, irritable bowel syndrome, asthma, cancers, arthritis, and mental health disorders [15][16][17][18][19][20][21][22]. The study of gut microbiome and microbial modulation using probiotics has extended to some of the most debilitating and severe mental disorders, including but not limited to major depressive disorder, bipolar disorder, and schizophrenia [23][24][25]. The immense potential of probiotics, particularly in treating mental disorders, has drawn a great deal of interest among researchers and clinicians.…”

“…Recent metaanalyses and systematic reviews have substantiated the efficacy of probiotic supplementation in the treatment of depressive disorder in human subjects. Depression scores based on validated clinical scales and certain biomarkers associated with depression including cortisol, proinflammatory cytokines and brain-derived neurotrophic factor (BDNF) levels were used to demonstrate the anti-depressive effect of probiotic intervention [25,27,30,31]. Clinical trials of probiotics in patients with depression, although limited compared to pre-clinical studies, have demonstrated comparable outcome in terms of mediating antidepressive effects, especially studies involving the measurement of biomarkers [18,[32][33][34][35].…”

The Influence of Probiotic Supplementation on Depressive Symptoms, Inflammation, and Oxidative Stress Parameters and Fecal Microbiota in Patients with Depression Depending on Metabolic Syndrome Comorbidity—PRO-DEMET Randomized Study Protocol

“…Certain microbiota interventions, e.g., introduction of the Mediterranean-style diet, intake of fermented food and dietary fiber, a plant-based diet, and consumption of prebiotics (oligosaccharides, fructans) may reduce the risk of developing depression [27], as well as MetS and its after-effects, e.g., chronic kidney disease (CKD) or cardiovascular diseases (CVDs) [28,29]. Furthermore, recent trial reports on using probiotics (live microorganisms that, if consumed in adequate amounts, bring the host health benefits [30]) demonstrated their usefulness in depression or anxiety outcome measures [31][32][33][34][35][36]. The results of the most recent meta-analysis on the use of probiotics in clinical depression demonstrated that probiotics are effective in reducing depressive symptoms when administered as an add-on; however, they do not seem to offer significant benefits when used as stand-alone treatment [36].…”

“…Furthermore, recent trial reports on using probiotics (live microorganisms that, if consumed in adequate amounts, bring the host health benefits [30]) demonstrated their usefulness in depression or anxiety outcome measures [31][32][33][34][35][36]. The results of the most recent meta-analysis on the use of probiotics in clinical depression demonstrated that probiotics are effective in reducing depressive symptoms when administered as an add-on; however, they do not seem to offer significant benefits when used as stand-alone treatment [36]. It has been suggested that the microorganisms can form a new group of drugs named "psychobiotics" [37], which makes future research in the area very promising.…”