Efficacy of Adjunct PRObiotics as Compared to the Standard Care in Moderate Unipolar Depression Among Geriatric Patients: A Randomized Double-Blind Placebo-Controlled Pilot Multi-Center Trial (PRODG).

OBJECTIVE

To evaluate the efficacy of adjunct probiotic supplementation ( Lactobacillus helveticus and Bifidobacterium longum ) alongside standard care compared to placebo in older adults with moderate unipolar depression.

METHODS

A randomized, double-blind, placebo-controlled pilot trial was conducted at two tertiary centers. Fifty-eight participants (≥ 60 years) with moderate depression were randomized 1:1 to receive daily probiotics or a placebo for 12 weeks, alongside standard antidepressant care. They were followed up for another 12 weeks. The primary outcome was depression response (≥ 50% Montgomery-Åsberg Depression Rating Scale [MADRS] score reduction). Secondary outcomes included anxiety (General Anxiety Disorder 7-Item [GAD-7]), cognition, quality of life (WHOQOL-BREF), serum brain-derived neurotropic factor (BDNF), and gut microbiota profile.

RESULTS

Mixed-effects models showed significant improvement over time in depressive symptoms (MADRS: F = 32.0, p < 0.001) and anxiety (GAD-7: F = 13.1, p < 0.001). Overall scores were lower in the probiotic group compared with the placebo group for both MADRS (F = 12.7, p = 0.001) and GAD-7 (F = 10.7, p = 0.002), although group × time interactions were not significant. Quality-of-life domains improved markedly (all F > 100, p < 0.001) without additional benefit from probiotics. Escitalopram-equivalent antidepressant dose and benzodiazepine use influenced selected outcomes. The probiotic group also had a significantly higher serum BDNF level and increased fecal abundance of supplemented strains vs. the placebo group. The attrition rate was > 50% over 24 weeks.

CONCLUSION

In this pilot PRODG trial, adjunct probiotics produced modest overall advantages for depressive and anxiety symptoms compared with placebo but did not enhance quality-of-life beyond usual improvement - both groups improved substantially, and trajectories over 24 weeks were largely parallel across follow-up.