Probiotics for adults with major depressive disorder Original paper

In this meta-analysis, probiotics were more effective than a placebo for reducing depression symptoms in adults with major depressive disorder.

The effect of probiotics compared to antidepressants for adults with depression.

The main outcome was depression symptoms measured using several validated questionnaires.

A total of 13,050 participants (ages 23–74) who had major depressive disorder.

A network meta-analysis of 42 randomized controlled trials was conducted. The trials were performed in Asia (17 trials), the Americas (13 trials), and Europe (3 trials), and at multinational centers (9 trials).

Probiotics, including Lactobacillus, Bifidobacterium, and Bacillus species, used as an add-on therapy to antidepressants were compared to a placebo. The following types of antidepressants were investigated: selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and ketamine/esketamine. The study duration was 6–24 weeks.

Compared to a placebo, probiotics reduced depression symptoms with a moderate effect size. Probiotics were estimated to be more effective than several antidepressants (i.e., brexpiprazole, cariprazine, citalopram, duloxetine, desvenlafaxine, ketamine, vilazodone, cortioxetine) and noninferior to the others.

Among all of the interventions, escitalopram (an SSRI) and probiotics were the most effective.

The comparative efficacies of probiotics and antidepressants were estimated based on the findings of separate studies, which can introduce bias.^[1] Until probiotics and antidepressants are directly tested in head-to-head comparisons, it’s unclear whether probiotics are truly superior/noninferior to antidepressants.

Only 1 trial investigated the efficacy of probiotics as a standalone treatment, while the others investigated probiotics as an add-on treatment to antidepressant therapy (most commonly SSRIs). As a standalone treatment, probiotics were as effective as first-line antidepressants (e.g., escitalopram) and novel (e.g., ketamine/esketamine) antidepressant therapies.