Probiotics Enhance Antidepressant Efficacy for Major Depressive Disorder

Summary: A probiotic blend comprising 14 strains of bacteria can enhance the treatment of major depressive disorder when used alongside antidepressants.

This pilot study highlights the potential of probiotics in promoting improvements in mood over an eight-week period. It is a pioneering exploration into how gut health, improved via probiotics, could pave the way for a novel approach to bolster mood and mental health.

According to the researchers, these encouraging results lay a robust foundation for further exploration in larger trials.

Key Facts:

  1. This research found that a 14-strain probiotic blend can potentially support improvements in depression and anxiety scores over an eight-week period when used alongside antidepressants.
  2. The study, one of the first in a Western population to demonstrate probiotics’ good tolerability and positive effects on mental health, offers a new potential pathway to support mood and mental health.
  3. A double-blind, randomized placebo-controlled design was employed in this pilot study. Participants were adults diagnosed with major depressive disorder who showed an incomplete response to antidepressants.

Source: King’s College London

A new study published today (14 June) in JAMA Psychiatry has found evidence that supplementing the diet with a probiotic blend containing 14 strains of bacteria can help individuals who are being treated for major depressive disorder with antidepressants.

The research, led by the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and in partnership with ADM Protexin, part of ADM, demonstrated the potential of probiotic supplementation to support improvements in multiple depression and anxiety scores over an eight-week period.

This shows a pill bottle.
Meaningful reported improvements were seen, measured against gold standard rating scales for depression and anxiety. Credit: Neuroscience News

The pilot study is one of the first trials in a Western population to show both good tolerability of probiotics and positive effects on mental health in adults with depression currently taking antidepressants.

According to the researchers leading the study, the results provide a strong basis to further investigate the benefits of this probiotic food supplement for supporting mood and mental health in a larger trial.

There is increasing evidence that the gut microbiota (the vast and dynamic community of microorganisms inhabiting the gut) has a role to play in the regulation of mood.

The study was a double-blind, randomised placebo-controlled study, designed as an initial exploration of whether improving gut health through the use of probiotics – supplements containing beneficial bacteria – could act as a new pathway for supporting mood and mental health.

In this pilot trial, 49 adults with diagnosed major depressive disorder and with an incomplete response to prescription antidepressants were provided with a widely available, proprietary 14 strain blend probiotic supplement or an identical placebo (24 receiving the probiotic).

Over the course of eight weeks, both groups demonstrated improvement in their symptoms, but greater improvements were seen in the probiotic group from week four onwards.

Meaningful reported improvements were seen, measured against gold standard rating scales for depression and anxiety.

Professor James Stone, the study’s senior investigator who began the work at King’s IoPPN and is now at Brighton and Sussex Medical School said, “Non- or partial response to antidepressants is a huge problem and this study is an important first step in exploring the therapeutic potential of probiotics as a treatment for depression.

“We found that probiotics were an acceptable and tolerable supplement in people already taking antidepressant medications. 

“This now paves the way for studies looking at whether we see these beneficial effects of probiotics on depression and anxiety in larger populations of patients.”

Dr. Viktoriya Nikolova, the study’s first author from King’s IoPPN said, “The gut-brain axis is a truly fascinating and rapidly evolving area of microbiome research. The findings of this pilot study are an important step forward in our understanding of the role of probiotics in mood and mental health.”

Dr Richard Day, VP of Medical Affairs at ADM said, “According to the World Health Organisation, an estimated 5% of adults suffer from depression, with a significant number failing to respond completely to standard treatment options.

“This trial is one of the few clinical studies to assess the benefits of supplementing the diet with probiotics alongside standard of care antidepressant medication. These exciting results add to our understanding of the link between the gut microbiome and mental health.”

This study was possible thanks to an MRC Industrial CASE PhD Studentship with ADM Protexin as the industry partner, and charitable donations from Freya Green.

Funding: It also received funding from the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

About this psychopharmacology and depression research news

Author: Amelia Remmington
Source: King’s College London
Contact: Amelia Remmington – King’s College London
Image: The image is credited to Neuroscience News

Original Research: Open access.
Acceptability, tolerability, and estimates of putative treatment effects of probiotics as adjunctive treatment in patients with depression: a randomized clinical trial” by James Stone et al. JAMA Psychiatry


Acceptability, tolerability, and estimates of putative treatment effects of probiotics as adjunctive treatment in patients with depression: a randomized clinical trial


The microbiota-gut-brain axis is a promising target for novel treatments for mood disorders, such as probiotics. However, few clinical trials have been conducted, and further safety and efficacy data are needed to support this treatment approach.


To provide acceptability and tolerability data and estimates of intervention effect size for probiotics as adjunctive treatment for patients with major depressive disorder (MDD).

Design, Setting, and Participants 

 In this single-center, double-blind, placebo-controlled pilot randomized clinical trial, adults aged 18 to 55 years with MDD taking antidepressant medication but having an incomplete response were studied. A random sample was recruited from primary and secondary care services and general advertising in London, United Kingdom. Data were collected between September 2019 and May 2022 and analyzed between July and September 2022.


Multistrain probiotic (8 billion colony-forming units per day) or placebo daily for 8 weeks added to ongoing antidepressant medication.

Main Outcomes and Measures  

The pilot outcomes of the trial were retention, acceptability, tolerability, and estimates of putative treatment effect on clinical symptoms (depression: Hamilton Depression Rating Scale [HAMD-17] and Inventory of Depressive Symptomatology [IDS] scores; anxiety: Hamilton Anxiety Rating Scale [HAMA] and General Anxiety Disorder [GAD-7] scores) to be used as indicators for a definitive trial.


Of 50 included participants, 49 received the intervention and were included in intent-to-treat analyses; of these, 39 (80%) were female, and the mean (SD) age was 31.7 (9.8) years. A total of 24 were randomized to probiotic and 25 to placebo.

Attrition was 8% (1 in the probiotic group and 3 in the placebo group), adherence was 97.2%, and there were no serious adverse reactions. For the probiotic group, mean (SD) HAMD-17 scores at weeks 4 and 8 were 11.00 (5.13) and 8.83 (4.28), respectively; IDS, 30.17 (11.98) and 25.04 (11.68); HAMA, 11.71 (5.86) and 8.17 (4.68); and GAD-7, 7.78 (4.12) and 7.63 (4.77). For the placebo group, mean (SD) HAMD-17 scores at weeks 4 and 8 were 14.04 (3.70) and 11.09 (3.22), respectively; IDS, 33.82 (9.26) and 29.64 (9.31); HAMA, 14.70 (5.47) and 10.95 (4.48); and GAD-7, 10.91 (5.32) and 9.48 (5.18).

Standardized effect sizes (SES) from linear mixed models demonstrated that the probiotic group attained greater improvements in depressive symptoms according to HAMD-17 scores (week 4: SES, 0.70; 95% CI, 0.01-0.98) and IDS Self Report scores (week 8: SES, 0.64; 95% CI, 0.03-0.87) as well as greater improvements in anxiety symptoms according to HAMA scores (week 4: SES, 0.67; 95% CI, 0-0.95; week 8: SES, 0.79; 95% CI, 0.06-1.05), but not GAD-7 scores (week 4: SES, 0.57; 95% CI, −0.01 to 0.82; week 8: SES, 0.32; 95% CI, −0.19 to 0.65), compared with the placebo group.

Conclusions and Relevance  

The acceptability, tolerability, and estimated effect sizes on key clinical outcomes are promising and encourage further investigation of probiotics as add-on treatment for people with MDD in a definitive efficacy trial.

Trial Registration Identifier: NCT03893162

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