Mental Health
Lauren Howell, PharmD
A study published in the August 2023 issue of JAMA Psychiatry suggests that probiotics could be used to bolster the response to antidepressant treatment in patients with major depressive disorder. The study found that individuals taking a daily probiotic for 8 weeks had a greater improvement in anxiety and depression symptoms than those taking a placebo.
It is a commonly accepted idea that targeting the microbiota–gut–brain axis is a promising pathway for new treatments for mood disorders, including major depressive disorder. With approximately 60% of individuals showing some degree of nonresponse to first-line treatments, there is a need for new options that could help fill this gap. Previous studies have found a reduction in depressive symptoms when probiotics are administered as adjunctive therapy to antidepressants. These studies, however, have lacked the ability to provide the safety and efficacy data that is needed for probiotics to be a widely used option in clinical practice.
The study by Nikolova and colleagues attempted to provide acceptability and tolerability data and estimates of intervention effect size for probiotics when used as adjunctive treatment for patients with major depressive disorder.
Study design
This study was a single-center, double-blind, placebo-controlled pilot randomized clinical trial. The participants consisted of 50 outpatients with a primary diagnosis of major depressive disorder and a Hamilton Depression Rating Scale (HAMD-17) score of greater than 13. The participants were all taking an antidepressant at a stable dose for at least 6 weeks and were not permitted to make any dosing changes during the study period.
Exclusion criteria included bipolar disorder, psychosis, eating disorders, personality disorders, substance dependence, suicidal ideation, serious medical illness, GI disease or surgery, use of antibiotics or probiotics in the past 12 weeks, current or regular use of GI medication, smoking, pregnancy, breastfeeding, and a vegan diet.
Participants were randomly assigned to either take four capsules of probiotic (2 x 109 colony-forming units per capsule) or four placebo capsules. The probiotic contained 14 strains of Bacillus subtilis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus delbruecki subsp bulgaricus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Lactobacillus salivarius, Lactococcus lactis, and Streptococcus thermophilus.
Participants attended visits at baseline, week 4, and week 8. The primary outcome was a change in depressive scores at week 8 based on the HAMD-17 score. Other outcomes included changes in anxiety, clinical status, and adherence. Information regarding adverse events and GI symptoms was also collected.
Results
Among the trial participants, baseline depression severity was moderate and 92% of the participants were taking an SSRI. Of the participants, 43% met the criteria for generalized anxiety disorder in addition to the major depressive disorder diagnosis. One difference noted between treatment groups was that all seven individuals who self-reported as Asian (non-Chinese) were randomized to the probiotic treatment group.
The researchers determined that adherence was high, with 97.2% of doses being taken as required based on a capsule count. No serious adverse reactions were reported during the study period and no participants withdrew from the study because of adverse effects. Nausea and indigestion were both reported as adverse reactions among the probiotic group, but these symptoms did not have to be treated with medication. The overall results of the study showed that depressive symptoms were improved in both study groups, but a greater reduction was seen among the individuals in the probiotic group from week 4.
Looking forward
This trial demonstrates the safety, acceptability, and therapeutic potential of probiotic therapy in patients with major depressive disorder. The treatment group showed greater improvement in depressive symptoms than the placebo group as seen in previous studies. With probiotics being a readily available and scalable intervention, this information suggests probiotics may be a new option for patients when used as adjunctive therapy to antidepressants.
Further research should be done to determine if the results of this study are replicable in patients being treated with other medication classes outside of SSRIs. Few studies have been performed to examine anxiety symptom response to probiotics and this area should continue to be explored as the findings of this study suggest that these symptoms may have been improved by the probiotic therapy. A larger-scale study with more participants should be conducted to continue to evaluate the efficacy of probiotics in major depressive disorder. ■