By the end of the 8-week pilot study, participants who had an incomplete response to antidepressants prior to taking probiotics scored better on measures of anxiety and depression versus placebo.
“This was a pilot study, designed as an initial exploration of whether improving gut health with probiotics could act as a new pathway for supporting mood and mental health,” study investigator Viktoriya Nikolova, PhD, Institute of Psychiatry, Psychology and Neuroscience at King’s College London, said in an interview.
“While very promising and exciting, our findings are only the first step, and larger trials are needed,” she noted.
The findings were published online in JAMA Psychiatry.
Gut-brain axis
It is estimated that up to 60% of people taking antidepressants for major depressive disorder (MDD) do not achieve full response.
With an eye on the so-called gut-brain axis as a treatment target for depression, the researchers conducted a meta-analysis of seven randomized controlled trials (RCT) in 2021 and found that probiotics appeared effective in reducing depressive symptoms when taken alongside antidepressants. The studies in this meta-analysis either reported poor adherence rates or did not investigate how well study participants tolerated probiotics.
To further investigate, Dr. Nikolova and team launched a pilot RCT by recruiting study participants from primary and secondary health care services, and through general advertising in London. Data were collected from September 2019 to May 2022.
They included 49 adults diagnosed with MDD with an incomplete antidepressant response, indicated by a score of greater than 13 on the Hamilton Depression Rating Scale-17 (HAMD-17).
Half of the participants were randomly assigned to receive a widely available, proprietary, 14-strain blend probiotic supplement, and half received placebo. Both groups took their study drug four times per day during the 8-week trial.
At baseline, 4 weeks, and 8 weeks, investigators assessed the participants for depression with the HAMD-17, the Inventory of Depressive Symptomatology (IDS) Self-Report, and anxiety with the Hamilton Anxiety Rating Scale (HAMA).
The majority of participants (80%) were female with a mean age of 32 years. Adherence was high, with 97% of the doses taken as required, and no adverse events were reported.
Standardized effect sizes from linear mixed models demonstrated that, when compared with the placebo group, the probiotic group had more improvement in depressive symptoms according to the HAMD-17 (week 4: SES, 0.70; 95% confidence interval, 0.01-0.98) and IDS Self Report (week 8: SES, 0.64; 95% CI, 0.03-0.87).
When compared with the placebo group, the probiotic group also experienced greater improvements in anxiety symptoms according to the HAMA (week 4: SES, 0.67; 95% CI, 0-0.95; week 8: SES, 0.79; 95% CI, 0.06-1.05).
Dr. Nikolova said a large follow-up trial is planned to further confirm the results.
Nutritional psychiatrist Drew Ramsey, MD, author of Eat to Beat Depression and Anxiety and assistant clinical professor of psychiatry at Columbia University, New York, said in an interview: “This randomized clinical trial adds to the considerable evidence that food choices impact depression outcomes.”
He further noted that, “in nutritional psychiatry, we recommend eating fermented foods as they have been shown to improve microbiome diversity and decrease markers of inflammation.”
Dr. Ramsey noted that the RCT used the equivalent colony-forming unit of a “single serving of kombucha.”
“In our clinical group and our nutritional psychiatry course for clinicians, we recommend fermented foods over probiotics as this is the most sustainable, evidence-based way to improve microbiome diversity,” said Dr. Ramsey, citing recent research by Gardner and colleagues at Stanford (Calif.) University.
“This is an industry-funded trial that adds to the evidence base but should be interpreted by patients and clinicians as promoting consumption of more kefir, kimchi, and kombucha, not that patients should take probiotics,” he said.