Table 3.
Major Depression Disorder.
| Major Depression Disorder | |||||
|---|---|---|---|---|---|
| Study | Study Design | Drugs and Dose | Cohort | Treatment Duration |
Results |
| Ginty et al., 2015 [80] |
Preliminary randomized and placebo-controlled trial | 1.4 g/day omega-3 (EPA + DHA) monotherapy |
23 (18 to 21 years) | 3 weeks | ↓ BDI scores over time |
| Mischoulon et al., 2015 [81] |
Randomized, double-blind, placebo-controlled trial | 1 g/day EPA or 1 g/day DHA or placebo | 196 (age not available) | 8 weeks | No differences |
| Park et al., 2015 [82] |
Randomized, double-blind, placebo-controlled trial | 1140 g/day EPA + 0.6 g/day DHA + standard therapy |
35 (18 to 65 years) | 12 weeks | No differences |
| Rapaport et al., 2016 [83] |
Proof-of-concept study | 1060 mg/day EPA + 260 mg DHA or 180 mg EPA + 900 mg/day DHA or placebo | 155 (18 to 80 years) | 8 weeks | Subjects with MDD and a high number of inflammatory biomarkers had a better response to EPA than the placebo and a lower response to DHA than the placebo |
| Young et al., 2017 [84] |
Randomized, placebo-controlled trial | 1.4 g/day EPA + 0.2 g/day DHA + 0.4 g/day other omega-3 + IF-PEP |
72 (7 to 14 years) | 12 weeks | ↓ co-occurring behavior symptoms |
| Gabbay et al., 2018 [85] |
Double-blind, placebo-controlled trial | 2:1 ratio of EPA to DHA: Initial dose of 1.2 g/day. Doses were raised in increments of 0.6 g/day every 2 weeks (maximum possible dose of 3.6 g/day, combined 2.4 g EPA + 1.2 g DHA) |
51 psychotropic medication-free adolescents with MDD (12 to 19 years) |
10 weeks | No differences |
| Jahangard et al., 2018 [86] |
Randomized, double-blind, placebo-controlled trial | 1000 mg/day omega-3 + 50–200 mg/day sertraline |
50 (18 to 65 years) | 12 weeks | ↓ depression, anxiety, sleep, and patients’ competencies to regulate their emotions |
| Hansen et al., 2019 [87] |
Randomised, multicenter, double-blind, placebo-controlled trial | 2800 UI /day Vit. D | 62 (18 to 65 years) | 12 weeks (+12 weeks follow up) | No differences |
| Tayama et al., 2019 [88] |
Randomized, double-blind, placebo-controlled trial | 1000 mg/day EPA + 500 mg/day DHA |
20 (18 to 75 years) | 12 weeks | No differences |
| Chahwan et al., 2019 [89] |
Randomized, triple-blind, placebo-controlled trial | Ecologic®Barrier (B. bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24, L. lactis W19 and L. lactis W58 (total cell count 1 × 1010 CFU/day) | 71 (23 to 48 years) | 8 weeks | No differences |
| Parletta et al., 2019 [90] |
Randomized, placebo-controlled trial | 200 mg/day EPA + 900 mg/day DHA + Mediterranean-style diet |
152 (18 to 65 years) | 26 weeks | ↓ depressive symptoms ↓ mental health |
| Karakula-Juchnowicz et al., 2019 [91] |
Double-blind, placebo-controlled clinical study protocol | 3 × 109 CFU L. helveticus Rosell®-52 + B. longum | 120 (18 to 60 years) | 12 weeks | ↓ GI symptoms ↓ depressive symptoms |
| Kazemi et al., 2019 [92] |
Randomized, controlled trial | L. helveticus + B. longum (probiotic) or galactooligosaccharides (prebiotics) or placebo | 110 (36.5 ± 8.03 years) | 8 weeks | Probiotics: ↓ BDI Prebiotics: no differences |
| De Koning et al., 2019 [93] |
Randomized, placebo-controlled trial | 1200 UI/day Vit. D | 155 (60 to 80 years) | 52 weeks | Increase of Vit. D serum level No clinical differences |
| Alavi et al., 2019 [94] |
Randomized clinical trial | 50,000 IU/week Vit. D | 78 older adults aged over 60 years | 8 weeks | Increase of Vit. D serum level ↓ GDS-15 |
| Saccarello et al., 2020 [95] |
Randomized, double-blind, placebo-controlled Study | 200 mg/day SAMe + 1 × 10⁹ CFU/day L. plantarum HEAL9 | 90 (18 to 60 years) | 6 weeks | ↓ Z-SDS |
| Trebatickà et al., 2020 [96] |
Randomized, double-blind, placebo-controlled trial | 2.4 g/day omega-3 (including 1 g EPA + 0.75 g DHA) or 2.467 g/day omega 6 (linoleic acid) |
60 children suffering from depressive disorder or mixed anxiety and depressive disorder (7 to 18 years) | 12 weeks | ↓ CDI score ↓ omega 6/omega-3 |
| Reininghaus et al., 2020 [97] |
Randomized, placebo-controlled trial | B. bifidum W23 + B. lactis W51 + B. lactis W52 + L. acidophilus W22 + L. casei W56 + L. paracasei W20 + L. plantarum W62 + L. salivarius W24 + L. lactis W19 daily | 82 (18 to 75 years) | 4 weeks | No differences |
| Reiter et al., 2020 [98] |
Monocentric, randomized, placebo-controlled trial | B. bifidum W23 + B. lactis W51+ B. lactis W52 + L. acidophilus W22 + L. casei W56 + L. paracasei W20 + L. plantarum W62 + L. salivarius W24 + L. lactis W19 daily | 61 (18 to 75 years) | 4 weeks | Reduction of IL6 level |
| Kaviani et al., 2020 [99] |
Randomized, double-blind, placebo-controlled trial | 50,000 IU/ 2 weeks vit. D | 56 (43 ± 11.15 years) | 8 weeks | ↓ depressive symptoms Increase of serum vit. D level |
| Zhu et al., 2020 [100] |
Randomized, placebo-controlled trial | 1600 mg/day Vit D | 158 with hypovitaminosis D (18 to 60 years) | 26 weeks | No differences in depression symptoms; improved anxiety symptoms |
| Libuda et al., 2020 [101] |
Randomized, placebo-controlled trial | 2640 UI vit. D/day | 113 with hypovitaminosis D (18 to 60 years) | 4 weeks | Increase of serum vit. D level ↓ DISYPS |
| Ho et al., 2021 [102] |
Randomized, double-blind, placebo-controlled pilot trial | 2 capsules (3 × 1010 CFU) L. Plantarum PS128 | 40 non-depressed patients with insomnia (20 to 40 years) | 4 weeks | ↓ BDI ↓ awakenings during the deep sleep stage |
| Joo Lee et al., 2021 [103] |
Randomized, double-blind, placebo-controlled Trial | 5 × 109 CFU probiotics (4.0 × 109 CFU for L. reuteri NK33 + 1 × 109 CFU for B. adolescentis NK98) | 156 healthy adults with subclinical symptoms of depression, anxiety, and insomnia (19 to 65 years) | 8 weeks | ↓ quality of sleep ↓ IL-6 ↓ depressive symptoms at 4 and 8 weeks of treatment ↓ anxiety symptoms at 4 weeks |
| Mischoulon et al., 2022 [104] |
Randomized, dose-finding clinical trial | 1 g/day or 2 g/day or 4 g/day EPA | 61 (age not available) | 12 weeks | 4 g/day EPA: ↓ depressive symptoms ↓ hs-CRP |
| Kaviani et al., 2022 [105] |
Randomized, double-blind, placebo-controlled trial | 50,000 IU cholecalciferol/2 weeks-1 | 56 (18 to 60 years) | 8 weeks | Increase of Vit. D serum level ↓ depressive symptoms |
| Schaub et al., 2022 [106] |
Randomized, placebo-controlled trial | 900 billion CFU/day (S. thermophilus + B. breve + B. longum + B. infantis + L. acidophilus + L. plantarum + L. paracasei + L. delbrueckii subsp. Bulgaricus) + treatment-as-usual | 47 (over 18 years) | 4 weeks | ↓ depressive symptoms |
| Ullah et al., 2022 [107] |
Monocentric, randomized, cross-over, double-blind, placebo-controlled clinical trial | 200 mg/day SAMe + 3 × 109 CFU/day L. helveticus Rosell®-52 + B. longum Rosell®-175 | 80 patients with SD or MDD (18 to 65 years) | 12 weeks | ↓ SD symptoms ↓ MDD symptoms |
| Schneider et al., 2023 [108] |
Secondary analysis of a randomized, placebo-controlled trial | Bifidobacteria 9 × 1010 CFU/g + Lactobacilli 8 × 1010 + S. salivarius subsp. Thermophilus 20 × 1010 resulting in a daily dose of 900 billion CFU/d + usual depression treatment | 60 (over 18 years) | 4 weeks | ↓ cognitive function (verbal episodic memory and working memory) |
| Nikolova et al., 2023 [109] |
Single-center, double-blind, placebo-controlled pilot randomized clinical trial | 2 × 109 CFU B. subtilis, B. bifidum, B. breve, B. infantis, B. longum, L. acidophilus, L. delbrueckii subsp bulgaricus, L. casei, L. plantarum, L. rhamnosus, L. helveticus, L. salivarius, L. lactis and S. thermophilus | 49 MDD taking antidepressant medication, but having an incomplete response were studied (18 to 55 years) |
8 weeks | ↓ depressive symptoms ↓ anxiety symptoms |
| Zhu et al., 2023 [110] |
Randomized, placebo-controlled trial | L. plantarum JYLP-326 2 vv/day | 60 anxious 22-year-old students | 3 weeks | ↓ depression ↓ anxiety ↓ insomnia |
Abbreviations: EPA = eicosapentaenoic acid; DHA = docosahexaenoic acid; MDD = Major depressive disorder; BDI = Beck Depression Inventory; GI = Gastrointestinal; CFU = colony forming units; HDRS = Hamilton depression rating scale; SAMe = S-adenosylmethionine; Z-SDS = Zung Self-Rating Depression Scale; SD = Subthreshold depression; GDS-15 = Geriatric Depression Scale-15; DISYPS-II = diagnostic system for mental disorders in childhood and adolescents, self-hand parent rating; CDI = Children’s Depression Inventory; IF-PEP = individual–family psychoeducational psychotherapy; B. = bifidobacterium or Bacillus; L. = Lactobacillus or Lactococco; S. = Streptococcus; Vit. = vitamin; IL = interleukin; ↓ = improvement of; hs-CRP = hs-C reactive protein.