Clostridium butyricum MIYAIRI 588 as Adjunctive Therapy for Treatment-Resistant Major Depressive Disorder: A Prospective Open-Label Trial

Abstract

Aim Up to 60% of depressed patients do not obtain sufficient relief from a course of antidepressant therapy, and these treatment-resistant major depressive disorder (TRD) patients are at increased risk for relapse, chronicity, persistent psychosocial impairments, and suicide. Probiotics actively participate in treatment of neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and depression remains unclear. We performed a prospective study to evaluate the effects of Clostridium butyricum MIYAIRI 588 (CBM588). Methods This was an 8-week open-label study to evaluate the efficacy and safety of CBM588 in combination with antidepressants in adult patients diagnosed with TRD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Forty antidepressant-treated inpatients were included. Patients were randomized to adjuvant treatment with CBM588 (n = 20) or control (n = 20). The primary endpoint was the change in the 17-item Hamilton Depression Rating Scale score from baseline to week 8. Secondary end points were changes in the Beck Depression Inventory and the Beck Anxiety Inventory scale scores from baseline to week 8. The Systematic Assessment of Treatment Emergent Events—General Inquiry was used to assess adverse effects. Results CBM588 (60 mg/d) in combination with antidepressants (flvoxamine, paroxetine, escitalopram, duroxetine, and sertraline) provided significant improvement in depression. All patients completed the trial, and 70% responded to treatment; the remission rate was 35.0%. No serious adverse events occurred. Conclusions These preliminary data suggest that CBM588 in combination with antidepressants is effective and well tolerated in the treatment of TRD. Further studies using a larger, double-blind, parallel-group design are warranted to confirm these findings.

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

“…These treated mice also showed upregulated central 5-HT, BDNF and GLP-1 receptors in the brain (Sun et al, 2018). Remarkably, the combination of C. butyricum with antidepressants reduced depression in about 70% of treatment-resistant MDD patients, of which 30% achieved remission (Miyaoka et al, 2018). These studies support the antidepressive efficacy of non-pathogenic C. butyricum.…”

Gut–Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions

“…It also reduced the inflammatory, immune and oxidative markers and mitochondrial stress via implicating PPAR-γ pathway. This mood illness has been improved when patients were treated with synbiotics [ 196 ], probiotics of multiple strains ( L. acidophilus , L. casei and B. bifidum ) [ 197 ], L. rhamnosus HN001 [ 198 ], and C. butyricum [ 199 ], and probiotic mixture [ 200 ]. In addition, supplements such as polyunsaturated fatty acids (PUFAS), especially eicosapentaenoic acid (EPA), and folate-based N-acetlycysteine are the strongest adjunctive treatment for depressive disorder [ 201 ].…”

Food & mood: a review of supplementary prebiotic and probiotic interventions in the treatment of anxiety and depression in adults

“…Furthermore, every study demonstrated a significant, quantitatively evident, decrease/improvement of symptoms and/or biochemically relevant measures of anxiety and/or depression for probiotic or combined prebiotic–probiotic use. This is observed regardless of the specific probiotic, method of administration or length of trial, across all test cohorts, irrespective of depression severity or additional comorbidities 20–26. The current evidence indicates: prebiotics are unlikely to be effective as an isolate therapy for depression within the timeframes investigated21 25; probiotics may be useful agents20–26; concomitant prebiotic–probiotic therapy may also be useful, though it is not obvious whether these agents function synergistically from this cohort of studies 21 25.…”

“…The 17 item Hamilton Depression Rating Scale (HAM-D-17) and Beck Depression Inventory II (BDI-II) were the two most commonly employed methods for evaluating subjects’ psychiatric condition pre/during/post invention. Probiotic/combined prebiotic–probiotic therapy significantly reduced patient scores on these tests in 6/7 studies 21–26. The exception, Rudzki et al ,20 found no link between probiotic use and changes in HAM-D-17 scores.…”