Probiotics May Improve Depression When Used With Antidepressants

Summary: In a randomized pilot trial, adding a daily probiotic supplement to standard antidepressant care produced modest but meaningful reductions in depression and anxiety symptoms among older adults with moderate unipolar depression. The 24-week study of 58 participants aged 60 and over used fecal microbiota profiling and serum brain-derived neurotrophic factor (BDNF) measurements to evaluate biological and clinical effects.

Both the probiotic and placebo groups showed substantial clinical improvement during follow-up, reflecting the effectiveness of standard antidepressant treatment. Nevertheless, the probiotic arm had distinct, measurable decreases in depressive and anxiety symptom scores and demonstrated biological evidence of change in BDNF levels and gut bacterial composition. These findings support probiotics as a safe, low-cost adjunctive option for late-life depression that warrants larger trials.

Key Facts

  • Targeted geriatric relief: Daily probiotic supplementation, given in addition to standard antidepressant care, produced modest but clinically meaningful reductions in depressive and anxiety symptoms in adults aged 60 and older.
  • Biomarker and microbiome tracking: The 24-week pilot trial combined validated psychological scales with serum BDNF measurement and fecal microbiota profiling to assess both clinical and biological effects.
  • Strong response to standard care: Both the probiotic and placebo groups showed major improvements over time, underscoring the benefit of usual antidepressant treatment in this population.
  • Quality of life results: Although psychologic symptom scores fell more in the probiotic group, there were no clear additional gains in overall self-reported quality of life compared with placebo.
  • Scalable public-health potential: Investigators plan a larger multicenter trial to confirm these findings and to develop affordable, scalable probiotic interventions for broader public-health use.

Source: Wiley

In brief: A pilot randomized, double-blind, placebo-controlled clinical trial published in the Journal of the American Geriatrics Society evaluated whether adjunct probiotic therapy could improve outcomes for older adults receiving standard antidepressant treatment. The study found modest but meaningful reductions in depressive and anxiety symptoms in the probiotic group compared with placebo, together with biological signs of change in serum BDNF and gut microbiota composition.

Fifty-eight adults in India aged 60 years or older with moderate unipolar depression were randomized 1:1 to receive either a daily probiotic containing Lactobacillus helveticus and Bifidobacterium longum or a matched placebo for 12 weeks, alongside usual antidepressant care, and then followed for another 12 weeks. Outcomes included depression symptom response measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), anxiety (GAD-7), cognition, quality of life (WHOQOL-BREF), serum BDNF, and fecal microbiome profiling.

Investigators reported significant improvement over time in both depressive (MADRS) and anxiety (GAD-7) symptoms across the whole sample. Overall symptom scores were lower in the probiotic group than in the placebo group for both MADRS and GAD-7, although formal group-by-time interactions did not reach significance. The probiotic group also showed a higher serum BDNF level and an increased fecal abundance of the supplemented strains versus placebo. Quality-of-life measures improved markedly in both groups without additional benefit attributable to probiotics. The study experienced more than 50% attrition across the 24 weeks.

“The results of our study are novel, and we are now planning a follow-up, larger-scale clinical trial due to the encouraging findings,” said co-corresponding author Dr. Saibal Das, MBBS, MD, DM, PhD, from the Indian Council of Medical Research – National Institute for Research in Bacterial Infections, Kolkata. Co–corresponding author Abhinaba Ghosh, MBBS, MSc, PhD, a physician-neuroscientist at Tata Medical Center, Kolkata, added: “My vision is to develop affordable healthcare solutions and make them available to the larger population for meaningful public health impact.”

Key Questions Answered:

Q: What is serum brain-derived neurotrophic factor (BDNF) and why is it relevant to depression?

A: BDNF is a protein that supports neuronal growth, plasticity, learning, memory, and cell survival. Chronically low BDNF levels are associated with neuronal atrophy and clinical depression. Measuring serum BDNF provides a biological signal that can indicate whether treatments are promoting neural repair and recovery processes in the brain.

Q: How might changing gut bacteria with probiotics influence mood in older adults?

A: The gut and brain communicate through the gut-brain axis, involving neural pathways (including the vagus nerve), immune signaling, and microbial metabolites. Beneficial probiotic bacteria can alter gut inflammation and generate neurotransmitter precursors or metabolites that modulate systemic and neural pathways, reducing inflammation and sending regulatory signals that can help stabilize mood and reduce anxiety.

Q: If the probiotic group improved, why are larger trials needed before broad clinical use?

A: This study was a pilot trial with a relatively small sample (58 participants) and high overall improvement in both arms from standard care. A larger, multi-center trial is necessary to separate probiotic-specific effects from general treatment response and placebo effects, establish reproducibility, determine optimal dosing and formulation, and develop clinical guidelines.

Editorial Notes:

  • This article was edited by a Neuroscience News editor.
  • The published journal paper was reviewed in full for accuracy.
  • Additional context was provided by editorial staff.

About this depression research news

Author: Sara Henning-Stout
Source: Wiley
Contact: Sara Henning-Stout – Wiley
Image: The image is credited to Neuroscience News

Original Research: Open access.
Title: Efficacy of Adjunct PRObiotics in Moderate Unipolar Depression in Geriatric Patients: A Randomized Double-Blind Multicentric Trial (PRODG).
Citation: Preeti Sinha et al., Journal of the American Geriatrics Society. DOI: 10.1111/jgs.70530


Abstract

Efficacy of Adjunct PRObiotics in Moderate Unipolar Depression in Geriatric Patients: A Randomized Double-Blind Multicentric Trial (PRODG)

Objective

To determine whether adjunct probiotic supplementation containing Lactobacillus helveticus and Bifidobacterium longum, given alongside standard antidepressant care, is more effective than placebo for older adults with moderate unipolar depression.

Methods

This randomized, double-blind, placebo-controlled pilot trial took place at two tertiary centers. Fifty-eight participants aged 60 years or older with moderate depression were randomized equally to receive daily probiotics or placebo for 12 weeks while continuing standard antidepressant treatment, and were followed for an additional 12 weeks. The primary outcome was a clinical depression response defined as a ≥50% reduction in MADRS score. Secondary outcomes included anxiety (GAD-7), cognition, quality of life (WHOQOL-BREF), serum BDNF levels, and gut microbiota composition from fecal samples.

Results

Mixed-effects modeling indicated 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 symptom scores were lower in the probiotic group compared with placebo for MADRS (F = 12.7, p = 0.001) and GAD-7 (F = 10.7, p = 0.002), though the interaction of group by time was not significant. Quality-of-life domains improved substantially in both groups (all F > 100, p < 0.001) without an added benefit from probiotics. Antidepressant dose equivalence and benzodiazepine use influenced some outcomes. The probiotic arm showed higher serum BDNF levels and increased fecal abundance of the supplemented strains relative to placebo. Attrition exceeded 50% over the 24-week period.

Conclusion

In this pilot PRODG trial, adjunct probiotic supplementation provided modest overall advantages for depressive and anxiety symptoms compared with placebo, accompanied by biological changes in BDNF and gut microbiota. However, probiotics did not yield additional gains in self-reported quality of life beyond the substantial improvements seen with standard antidepressant care. Larger, multi-center trials are needed to confirm these results and define clinical recommendations for probiotics in geriatric depression.