probiotics illustration

A recent study on probiotics shows promising preliminary results for the treatment of depression and depressive disorders.

The Changing Face of Depression Treatment

Not long ago, a person diagnosed with depression didn’t have an extensive list of treatment options. Traditional care for people with a depressive disorder or a mood disorder with depressive symptoms included psychotherapy/counseling and medication.

Toward the end of the 20th century, innovative clinicians incorporated what people now call complementary, supportive, or adjunct approaches to support people with depression. These included lifestyle changes like improving diet, getting plenty of exercise or activity every day, and improving sleep. When those approaches helped, clinicians added complementary techniques like yoga, mindfulness, meditation, and various stress reduction and wellness activities.

More recently, the Food and Drug Administration approved new techniques for depression treatment including transcranial magnetic stimulation (TMS), IV ketamine infusions, and treatment with Spravato®. TMS is a brain stimulation therapy for people with severe, treatment-resistant depression. It’s a much milder stimulation therapy then electroconvulsive therapy (ECT), which has been in use for decades, but only recommended in extreme cases. IV ketamine and Spravato® belong to a new approach to mental health treatment called psychedelic therapy.

To learn more about TMS, please read our treatment page here:

Transcranial Magnetic Stimulation (TMS)

To learn more about psychedelic therapy, please read our treatment page here:

Ketamine and Spravato®

Those treatments offer hope to people with treatment-resistant mental health disorders who don’t experience symptom relief from a standard treatment protocol with psychotherapy, antidepressants, and typical lifestyle changes.

Now, there’s another approach that may help people with treatment-resistant depression experience symptom relief: treatment with probiotics. The idea behind this approach is that the relative health of gut microbiome – we’ll define that below – can have a direct and measurable effect on the presence and severity of the symptoms of depression.

We’ve published an article on this topic before. To learn about the impact of the gut microbiome on schizophrenia, please navigate to the blog section of our website and read this article:

Can an Unhealthy Gut Lead to Treatment-Resistant Schizophrenia

That article sets the stage for a discussion of the gut microbiome on mental health, and presents information about the impact of probiotics on schizophrenia. This article is the impact of the gut microbiome on depression, a mental health disorder that affects 280 million people worldwide, and roughly 21 million people in the United States.

The Gut Microbiome and Depression: What’s the Connection?

The phrase gut microbiome refers to all the species bacteria that live in our digestive tract. Bacteria inhabit our stomach, small intestine, and large intestine. Each gram of content from the large intestine and small intestine contains a staggering number of bacterial cells. While they’re difficult to count, experts estimate each gram contains between one hundred billion and one hundred trillion bacterial cells.

That’s our gut microbiome: the entirety of the bacterial cells that live in our gut, or digestive system.

The gut microbiome is an important part of our overall health. When our gut microbiome is out of balance, we develop gut dysbiosis. Dysbiosis in the gut microbiome is associated with several mental health disorders, including:

  • Anxiety
  • Depression
  • Autism
  • Schizophrenia

Previous studies show promising results with probiotic treatment for people with various mental health disorders:

  • Probiotics and prebiotics can reduce severity of symptoms of schizophrenia, anxiety, and depression
  • Probiotics and prebiotics can reduce the positive and negative symptoms of psychosis and psychotic disorders.

These studies are important for a variety of reasons. Primarily, they’re important because for many people – close to 30 percent of people diagnosed with depression – the standard approaches don’t yield significant symptom relief. Typical treatment with psychotherapy and antidepressants can help, of course. But in people with severe cases or cases that don’t respond to treatment, the symptoms never meet criteria for remission, continue to cause psychological and emotional distress, and continue to disrupt daily life.

Can Treatment With Probiotics Reduce Depressive Symptoms?

Previous research establishes the connection between gut dysbiosis and mental health disorders. Additional research confirms the positive impact of probiotics and prebiotics on the symptoms of schizophrenia, anxiety, depression, and psychosis. However, the research base isn’t broad, and clinicians need more evidence before treatment that focuses on the gut microbiome can move beyond a recommended lifestyle change – i.e., as part of improving overall diet – and become a recognized first-line or supportive, complementary treatment.

The study we discuss in this article –  “Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression” – seeks to add to the body of research around the use of probiotics in mental health treatment. Here’s the question at the center of their research, in their own words:

“Are probiotics an acceptable, tolerable, and potentially efficacious adjunctive treatment for depression?”

Most of us know what probiotics are, even if we couldn’t generate a list of probiotics when asked. We find probiotics in typical foods in the grocery store like yogurt or kefir. It’s also present in health-oriented beverages made from kombucha and various products that involve fermentation. Technically speaking, a probiotic is defined as:

“A microorganism that when consumed in food or as a dietary supplement maintains or restores beneficial bacteria in the digestive tract.”

To answer their primary research question, the research team recruited 50 patients diagnosed with major depressive disorder (MDD) and separated them into two groups. One group received probiotics and the other group received a placebo. All patients in the study were currently taking an antidepressant medication with unsatisfactory results.

The team established the following primary outcome metrics for the study:

  • Retention/Adherence
  • Acceptability
  • Tolerability
  • Efficacy

To collect data on potential efficacy of symptom reduction, researchers administered four psychiatric screenings at baseline. For depressive symptoms, they administered the Hamilton Depression Rating Scale (HAMD-17) and Inventory of Depressive Symptomatology (IDS). For the symptoms of anxiety, they administered the Hamilton Anxiety Rating Scale (HAMA) and General Anxiety Disorder (GAD-7).

After identifying baseline scores, the research team collected data at 4 weeks and 8 weeks post-initiation. In addition, they assessed the symptom reduction efficacy results with a metric called Clinical Global Impression (CGI), which measures treatment response and symptom severity in studies of patients with clinical mental health diagnoses.

Let’s take a look at what they found.

Probiotics and Depression Treatment: The Results

We’ll start with the simplest metrics: retention, acceptability, and tolerability.

Retention

Participants took 97.2% of doses of medication offered during the study. Treatment adherence was very high.

Acceptability

Participants reported no serious adverse reactions. Acceptability was very high.

Tolerability

A total of 16 patients in the probiotic group reported mild gastrointestinal symptoms during the study, which were temporary, and did not require medication for improvement. Treatment with probiotics was well tolerated.

That’s the data on the first component of the study.

Researchers wanted to know:

  1. Whether people would actually follow the protocols as established. They did.
  2. Whether the treatment involved serious side effects. It didn’t.
  3. Whether the side effects prevented participants from continuing the study. They didn’t/

Information like that helps clinicians understand what the treatment experience will be like for their patients, and what potential pitfalls are involved in any new treatment. This data indicates patients will likely encounter few problems participating in and completing a depression treatment protocol with probiotics.

Now let’s take a look at the potential impact on symptoms of depression and anxiety.

Probiotics: Effect on Depressive Symptoms

HAMD-17:

  • Probiotic group
    • Baseline: 16.5
    • 4 weeks: 11.0
    • 8 weeks: 8.83
  • Placebo group:
    • Baseline: 17.3
    • 4 weeks: 14.04
    • 8 weeks: 11.09

ISD-SR:

  • Probiotic group
    • Baseline: 37.5
    • 4 weeks: 30.17
    • 8 weeks: 25.04
  • Placebo group
    • Baseline: 37.0
    • 4 weeks: 33.82
    • 8 weeks: 29.64

HAMA:

  • Probiotic group
    • Baseline: 15.8
    • 4 weeks: 11.71
    • 8 weeks: 8.17
  • Placebo group
    • Baseline: 16.1
    • 4 weeks: 14.7
    • 8 weeks: 10.95

GAD-7:

  • Probiotic group
    • Baseline:10.6
    • 4 weeks: 7.78
    • 8 weeks: 7.63 (28%)
  • Placebo group
    • Baseline: 11.0
    • 4 weeks: 10.91
    • 8 weeks: 9.48 (14%)

Finally, we’ll share data from the Clinical Global Impression (CGI), which measured the degree of symptom improvement in each participant.

Symptom Improvement: Probiotic Impact on Depression and Anxiety

Probiotic Group

  • 4 weeks:
    • Very much improved: 17%
    • Much improved: 21%
    • Small improvement: 46%
    • No change: 16%
  • 8 weeks:
    • Very much improved: 21%
    • Much improved: 33%
    • Small improvement: 38%
    • No change: 8%

Placebo Group

  • 4 weeks:
    • Very much improved: 0%
    • Much improved: 16%
    • Small improvement: 17%
    • No change: 56%
  • 8 weeks:
    • Very much improved: 0%
    • Much improved: 32%
    • Small improvement: 36%
    • No change: 32%

When reading these results, keep in mind that all participants in the study also took standard anti-depressant medication during the study period. Researchers designed the probiotic protocol as an adjunct, supporting, or complementary treatment to add to standard treatment with traditional psychiatric medication. Therefore, it’s important to pay attention to the difference in treatment response between the two groups, rather than the presence or absence of a response overall.

We’ll discuss these results below.

Probiotics and Depression: Is This a Feasible Adjunct Treatment?

In a word, yes.

When we look at the scores on the scales that measure depressive symptoms, we see a significant difference between the probiotic group and the placebo group. After 8 weeks, the probiotic group showed a 46 percent reduction on the HAMD-17 scale and a 33 percent reduction on the ISD-R scale, compared to a 36 percent reduction and a 21 percent reduction for the placebo group, respectively.

When we look at the scores on the scales that measure the symptoms of anxiety, we also see significant differences between the probiotic group and the placebo group. After 8 weeks, the probiotic group showed a 48 percent reduction on the HAMA scale and a 28 percent reduction on the GAD-7 scale, compared to a 33 percent reduction and a 14 percent reduction for the placebo group, respectively.

The probiotic group also showed significantly superior symptom improvement at both 4 and 8 weeks as measured by the CGI, a clinician-scored assessment of depression and anxiety symptoms.

All those findings have real meaning for people with depression who don’t respond well to standard treatment with psychotherapy and antidepressant medication. They show that when combined with traditional approaches, probiotics can help reduce symptoms.

That’s an important finding – and there’s one more thing that makes this study even more relevant: the ease of the treatment. Patients took two supplement tablets a day for 8 weeks. That’s it – and that’s about as simple and inexpensive as mental health treatment gets.

We’ll give the next-to-last last word on this topic to the study authors:

“This pilot study suggest[s] that 8-week adjunctive treatment with a multistrain probiotic is acceptable and tolerable for adults with MDD. The estimated effect sizes on key clinical outcomes are promising and encourage further investigation in a definitive efficacy trial.”

We’ll keep an eye on the news for the results of a definitive efficacy trial, and report them here as soon as they’re available.