Probiotics an effective addition to antidepressants for DCS

When used as an adjunctive treatment, probiotic supplements reduce symptoms in patients with major depression, the results of a randomized placebo-controlled trial suggest.

At the end of the 8-week pilot study, participants who had an incomplete response to antidepressants before taking the probiotics scored better on measures of anxiety and depression than placebo.

“This was a pilot study, designed as an initial exploration of whether improving gut health with probiotics could act as a new pathway to support mood and mental health,” explained Viktoriya Nikolova, PhD, Institute of Psychiatry, Psychology and Neuroscience at King’s College. London, UK, he said Medscape Medical News.

“Although very promising and exciting, our results are only the first step and larger studies are needed,” he noted.

The results were published online on June 14 JAMA Psychiatry.

Gut-brain axis

It is estimated that up to 60% of people taking antidepressants for major depressive disorder (MDD) do not achieve a complete response.



Dr. Viktoriya Nikolova

With an eye to the so-called gut-brain axis as a treatment target for depression, researchers conducted a meta-analysis of seven randomized controlled trials (RCTs) in 2021 and found that probiotics appeared effective in reducing depressive symptoms when taken along with antidepressants. The studies in this meta-analysis either reported poor adherence rates or did not investigate how well study participants tolerated probiotics.

To investigate further, Nikolova and team launched a pilot RCT by recruiting study participants from primary and secondary health services and through general publicity in London. The data was collected from September 2019 to May 2022.

They included 49 adults diagnosed with MDD with an incomplete antidepressant response, indicated by a score 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 a placebo. Both groups took the study drug four times a day during the 8-week trial.

At baseline, 4 weeks, and 8 weeks, researchers assessed participants for depression with the HAMD-17, Inventory of Depressive Symptoms (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 doses taken as needed, and no adverse events were reported.

Standardized effect sizes (SES) from linear mixed models demonstrated that, compared with the placebo group, the probiotic group had greater improvement in depressive symptoms according to HAMD-17 (week 4: SES, 0.70; 95% CI , 0.01 – 0.98) and IDS Self Report (week 8: SES, 0.64; 95% CI, 0.03 – 0.87).

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).

Nikolova said a large follow-up study is planned to further confirm the findings.



Dr Drew Ramsey

Nutritional psychiatrist Drew Ramsey, MD, author of Eat to beat depression and anxiety and assistant clinical professor of psychiatry at Columbia University College of Physicians and Surgeons in New York City, said Medscape Medical News: “This randomized clinical trial adds to the considerable evidence that food choices affect the outcomes of depression.”

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.

Ramsey noted that the RCT used the colony-forming unit equivalent of a “single serving of kombucha.”

“In our clinical group and in our Nutritional Psychiatry for Physicians class, we recommend fermented foods over probiotics as this is the most sustainable and evidence-based way to enhance microbiome diversity,” Ramsey said, citing recent research by Gardner et al at Stanford.

“This is an industry-funded study that adds to the evidence base, but it should be interpreted by patients and clinicians as promoting the consumption of more kefir, kimchi and kombucha, not that patients should be taking probiotics,” she said.

A key place for probiotics in mental health



Dr. Uma Naidoo

Commenting for Medscape Medical NewsUma Naidoo, MD said, “As I shared during my first book, This is your brain on food, there is a real place for the use of probiotics in mental health, including the importance of the gut-brain connection.” Naidoo is the director of nutritional and metabolic psychiatry at Massachusetts General Hospital and of nutritional psychiatry at the MGH Academy.

She noted that when a person stops using a probiotic after trying it, the positive changes in the gut are reversed, so “staying consistent about taking the probiotic is important if you’ve found it helpful for your mood.”

Naidoo added that “each person’s gut microbiome is so unique that it’s likely that not all humans will have the same reaction to a probiotic.”

“Eating foods with live probiotics can also benefit gut health and, therefore, mood,” she said. The same goes for the consumption of fermented foods with active live cultures.”

The study was funded by a CASE Industrial Doctoral Scholarship from the Medical Research Council with ADM Protexin (supplier of probiotics) as the industrial partner and with additional support from Freya Green. Nikolova received grants from the Medical Research Council and ADM Protexin during the conduct of the study, as well as personal honoraria from Janssen outside of the submitted work.

JAMA Psychiatry. Published online June 14, 2023. Full text

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