Details of the articles, along with each study's modified CASP appraisal score
| Author, year, study type, location | Subjects | No. of subjects, F/M ratio | Days of intervention, type of intervention | Method of administration, dose | Measured outcome | Study appraisal score |
| Rudzki et al (2019), RCT, Poland20 | Patients with clinically diagnosed MDD, that are also on an SSRI treatment regimen in an outpatient setting | 79 43:17 (19 subjects lost to follow-up with gender unspecified in report) | 56 Probiotic: Lactobacilus plantarum 299 v |
Weeks 0–8:
2 probiotic containing capsules, 1 in the morning, 1 at night. Dose: 10× 109 CFU | Primary: Psychiatric symptoms: Hamilton Depression rating scale (HAM-D-17) <=>; Symptom checklist-90 <=>; Perceived Stress Scale-10 <=>. Cognitive functions: Work speed in attention and perceptivity test \/; California Verbal Learning Test \/; Ruff-figural fluency test <=>; Stroop Test parts A & B <=>. Biochemical measures in systemic circulation: kynurenine (KYN) \/; 3-hydroxykynurenine:KYN ratio \/; KYN:TRP ratio <=>; TRP <=>; kynurenic acid <=>; anthranilic acid <=>; 3-hydroxy anthranilic acid <=>; TNFα <=>; IL-6 <=>; IL-1b <=>; cortisol plasma concentrations <=>. | 10 |
| Majeed et al (2018), RCT, India23 | Patients with clinically diagnosed MDD and IBS | 40 17:3 | 90, further follow-up at day 105 Probiotic: Bacillus coagulans MTCC 5856 |
Weeks 0–11:
1 probiotic containing tablet daily Dose: 600 mg tablet containing 333.3 mg of B. coagulans – 2×109 CFU | Primary measures: Depression symptoms: HAM-D-17 \/; Montgomery-Asberg Depression Rating \/. Secondary measures: Clinical Global Impression Improvement Rating Scale \/; Clinical Global Impression Severity Rating Scale \/; Gastrointestinal Discomfort Questionnaire (GI-DQ) \/; Modified Epworth Sleepiness Scale (mESS)\/; Montgomery-Asberg Depression Rating Scale \/; Centre for Epidemiological Studies Depression Scale \/; Irritable bowel syndrome quality of life questionnaire (IBS-QoL) \/ | 8 |
| Kazemi et al (2018), RCT, test, test, control, Iran21 | Patients with clinically diagnosed MDD, also on SSRI treatment regimen in an outpatient setting | 110 enrolled, 81 completed trial, all participants accounted for 78:32 | 56 Probiotics: Lactobacillus helveticus Bifidobacterium longum OR Prebiotic: galacto-oligosaccharide |
Probiotic: 5 g sachet given once daily Dose: ≥10 × 109 CFU of bacterial strains (both strains cumulatively equal ≥10 × 109 CFU) Prebiotic: 5 g dose galacto-oligosaccharide +0.2% excipient. | Primary outcomes: Depression symptoms: Beck Depression Inventory (BDI-II) \/ for probiotic, <=> prebiotic. Secondary outcomes: Biochemical measures: Serum KYN:TRP <=> for probiotic, <=> prebiotic; KYN:TRP once adjusted for serum isoleurine = \/ probiotic, <=> prebiotic; TRP: isoleurine ratio \/ for probiotic, <=> prebiotic; tryptophan:branched chain amino acid ratio <=> probiotic, <=> prebiotic. | 10 |
| Miyaoka et al (2018), open label case–control, Japan24 | Patients with treatment resistant MDD, who are taking SSRIs | 40 24:16 | 56 Probiotic: Clostridium butyricum MIYAIRI 588 (CBM588) |
Weeks 0–4:
1 capsule daily Dose: 40 mg Weeks 2–8: 1 capsule daily Dose: 60 mg | Primary outcomes: Depression symptoms: HAD-17 \/; Secondary outcomes: Depression symptoms: BDI-II \/. Anxiety symptoms: Beck Anxiety Inventory Score \/. | 5.5 |
| Ghorbani et al (2018), RCT, Iran25 | Patients with clinically diagnosed moderate severity depression | 40 28:12 | 70 Probiotics: Lactobacilus casaei Lactobacillus acidophilus Lactobacillus bulgarigus Lactobacillus rhamnosus Bifidobacterium breve Bifidobacterium longum Streptococus thermophilus AND Prebiotic: Fructo-oligosaccharide |
Weeks 0–4:
1 tablet daily fluoxetine Dose: 20 mg Weeks 4–10: 1 tablet fluoxetine 2 synbiotic capsules daily Dose: 20 mg fluoxetine; 2 synbiotic capsules Capsule content: 500 mg of probiotics: (Lactobacillus casaei 3×108 CFU/g; Lactobacillus acidophilus 2×108 CFU/g; Lactobacillus bulgarigus 2×109 CFU/g; Lactobacillus rhamnosus 3×108 CFU/g; Bifidobacterium breve 2×108 CFU/g; Bifidobacterium longum 1×109 CFU/g; Streptococus thermophilus 3×108 CFU/g + 100 mg prebiotics: mg fructo-oligosaccharide | Primary outcome: HAD-17 \/. | 9.5 |
| Bambling et al (2017), case series, Australia26 | Patients with resistant depression and multiple, poor response to treatment in the past | 12 8:4 | 56, further follow-up at day 112 Probiotics: Lactobacillus acidophilus Bifidobacterium bifidum Streptoccocus thermophiles |
Weeks 0–8:
2 capsules daily Dose: 2×1010 CFU of all microorganisms with 1600 mg magnesium oratate | Primary outcomes: Psychiatric symptoms: Mini International Neuropsychiatric Interview (MINI,5) \/; BDI-II \/; Outcome Questionnaire 45 (OQ45) \/; Quality of Life Measure \/. | 6 |
| Akkasheh et al (2016), RCT, Iran22 | Patients with clinically diagnosed MDD | 40 34:6 | 56 Lactobacillus acidophilus Lactobacillus casei Bifidobacterium bifidum |
Weeks 0–8:
1 capsule daily Dose: Lactobacillus acidophilus (2×109 CFU/g) Lactobacillus casei (2×109 CFU/g) Bifidobacterium bifidum (2×109 CFU/g) | Primary outcomes: Depression symptoms: BDI-II \/; Secondary outcomes: Biochemical measures: Serum insulin \/; homeostasis model assessment of insulin resistance \/; serum hs-CRP concentration \/; fasting plasma glucose <=>; homeostatic model assessment of β cell function <=>; quantitative insulin sensitivity check index <=>; lipid profiles <=>; total antioxidant capacity levels <=>. | 9.5 |
Studies are identified with the patient group, participant number, intervention type and regimen detailed. The measured outcomes from which any effect could be observed, along with the findings of the studies, are detailed.
/\ represents a statistically significant increase in a measured outcome parameter for the test versus control group; \/ indicates a statistically significant decrease in a measured outcome parameter; <=> indicates that no statistically significant change was detected between the groups.
A modified-CASP appraisal score is included. The modified-CASP appraisal tool is a novel evaluative method that allows a numerical value from 0 to 12 to be calculated for each article based on its performance with respect to the traditional CASP appraisal framework criteria. A higher score out of 12 indicates a better quality article. This information can be integrated with the findings in table 3, which detail the extent to which each study appears to be affected by various biases in order to augment a thorough critical analysis of the dataset.
BDI-II, Beck Depression Inventory II; CASP, Critical Appraisal Skills Programme; CFU, colony forming units; F/M, female/male; GI-DQ, Gastrointestinal Discomfort Questionnaire; HAM-D-17, 17 item Hamilton Depression Rating Scale; hsCRP, high sensitivity C-reactive protein; IBS, irritable bowel syndrome; IBS-QoL, Irritable Bowel Syndrome Quality of Life questionnaire; IL, interleukin; KYN, kynurenine ; MDD, major depressive disorder; mESS, modified Epworth Sleepiness Scale; MINI,5, Mini International Neuropsychiatric Interview; OQ45, Outcome Questionnaire 45 ; SSRI, selective serotonin reuptake inhibitor; TNF, tumour necrosis factor; TRP, tryptophan.