Table 4.
Bipolar Disorder.
| Bipolar Disorder | |||||
|---|---|---|---|---|---|
| Study | Study Design | Drugs and Dose | Cohort | Treatment Duration |
Results |
| Sharpley et al., 2014 [111] |
Randomized, double-blind, placebo-controlled trial | 2.5 mg/day folic acid | 112 with familial risk of mood disorder (14 to 24 years) | 156 weeks | No differences |
| Fristad et al., 2015 [112] |
Randomized, placebo-controlled trial | 2000 mg/day omega-3 (including 1400 mg EPA + 200 mg DHA) and IF-PEP vs. AM using a 2 × 2 design |
23 (7 to 14 years) | 12 weeks | Manic symptoms improved over time without significant treatment effects Effect of IF-PEP on child depression compared with AM was medium to large Effect of omega-3 on depression was medium |
| Wozniak et al., 2016 [113] |
Pilot study | 1650 mg/day EPA + DHA + 2000 mg inositol or 1650 mg/day EPA + DHA + placebo or 2000 mg inositol + placebo | 24 (5 to 12 years) | 12 weeks | Omega-3 + inositol: ↓ symptoms of mania and depression |
| Marsh et al., 2017 [114] |
Randomized, double-blind, placebo-controlled trial | 5000 UI/day Vit. D | 33 patients with vit. D deficiency (18 to 70 years) | 12 weeks | No differences in depressive symptoms |
| Nierenberg et al., 2017 [115] |
Open trial proof-of-concept registry | 15 mg/day L-methyl folate | 10 (18 to 75 years) | 6 weeks | ↓ MADRS ↓ Cohen’s d ↓ YMRS |
| Dickerson et al., 2018 [116] |
Randomized, parallel two-group, placebo-controlled trial | L. rhamnosus strain GG + B. animalis subsp. Lactis strain Bb12 (dosage not available) | 66 patients who have been recently discharged following hospitalization for mania (18 to 65 years) | 24 weeks | ↓ rehospitalization |
| Mehrpooya et al., 2018 [117] |
Double-blind placebo-controlled trial | 200 mg/day Coenzyme Q10 | 69 (18 to 65 years) | 8 weeks | ↓ depressive symptoms |
| Vesco et al., 2018 [118] |
Randomized controlled trial | 1.87 g/day omega-3 or PEP or PEP + omega-3 |
95 (7 to 14 years) | 12 weeks | Omega-3: ↓ executive functions ↓ dysphoric mood ↓ irritability ↓ self-esteem |
| Toniolo et al., 2018 [119] |
Double-blind, placebo-controlled trial | 6 g/day creatine monohydrate | 35 (18 to 59 years) | 6 weeks | No differences |
| McNamara et al., 2020 [120] |
Placebo-controlled proton magnetic resonance spectroscopy trial | 2130 mg/day omega-3 (EPA + DHA) | 42 children with depressive symptoms with at least one parent with DB (9 to 21 years) | 12 weeks | No clinical differences Increase of erythrocyte EPA + DHA levels |
| Ashton et al., 2020 [121] |
Sub-study, randomized, placebo-controlled trial | N-acetyl-cysteine or mitochondrial-enhancing nutraceuticals (including N-acetyl-cysteine) | 133 (21.3 to 72 years) | 16 weeks | Better diet quality (irrespective of treatment and time): ↓ general depression and bipolar depression symptoms Greater clinician-rated improvement |
| McPhilemy et al., 2021 [122] |
Randomized, placebo-controlled trial | 1 g/day EPA+ 1 g/day DHA | 80 (over 18 years) | 52 weeks | No differences |
| Badrfam et al., 2021 [123] |
Randomized, double-blind, placebo-controlled trial | 80 mg/day vit. B6 + lithium (gradually increased dose to a therapeutic level of 0.8–1.2) | 50 (18 to 65 years) | 8 weeks | No differences |
| Fristad et al., 2021 [124] |
Naturalistic follow-up study | 2000 mg/day omega-3 (including 1400 mg EPA + 200 mg DHA) and IF-PEP vs. AM using a 2 · 2 design |
38 (11 to 19 years) | 104–260 weeks | ↓ depressive symptoms ↓ youth emotion regulation skills and family communication |
| Sabouri et al., 2022 [125] |
Randomized, double-blind, placebo-controlled trial | Probiotics | 38 (age not available) | 8 weeks | No differences in markers of inflammation and oxidative stress |
| McNamara et al., 2022 [126] |
Placebo-controlled trial | 2130 mg/day omega-3 (EPA + DHA) | 39 depressed youth at high risk for developing BD type I (9 to 21 years) | 12 weeks | ↓ functional amygdala–right inferior temporal gyrus connectivity ↓ depressive symptoms Increase of erythrocyte EPA + DHA levels |
| Saunders et al., 2022 [127] |
Randomized, parallel-group, modified double-blind, controlled | 1.5 g omega-3 (EPA + DHA) + low omega-6 vs. control diet standardized (150 mg omega-3 + omega-6) | 82 (over 18 years) | 48 weeks (4-8-12 weeks of diet exposure) | No differences |
| Wozniak et al., 2022 [128] |
Randomized, double-blind, placebo-controlled trial | 1650 mg/day EPA + DHA + 2000 mg inositol or 1650 mg/day EPA + DHA + placebo or 2000 mg inositol + placebo | 69 (5 to 12 years) | 12 weeks | ↓ YMRS (inositol + omega-3) ↓ HDRS (inositol + omega-3) ↓ antimanic and antidepressant effects |
| Eslahi et al., 2023 [129] |
Randomized, double-blind, placebo-controlled trial | 2 g/day omega-3 (including 180 mg EPA + 120 mg DHA) | 60 (16 to 60 years) | 8 weeks | ↓ depression score ↓ TNF-α ↓ IL-6 ↓ hs-CRP |
| Zailani et al., 2024 [130] |
Pilot randomized, placebo-controlled trial | 420 mg/day EPA + 220 mg/day DHA + 0.2 mg/day tertiary-butylhydroquinone + 2.0 mg/day vit. E |
31 (18 to 65 years) | 26 weeks | ↓ recurrence of bipolar depression ↓ depressive symptoms |
| Zandifar et., 2024 [131] |
Randomized, placebo-controlled trial | 100 mg/day vit. B1 or 40 mg/day vit. B6 or placebo + 900–1200 mg lithium | 66 (18 to 65 years) | 8 weeks | B6: ↓ symptoms during a manic episode + ↓ sleep status B1: no mood improvement, ↓ sleep status |
Abbreviations: EPA = Eicosapentaenoic acid; DHA = Docosaesaenoic acid; IL-6 = interleukin 6; YMRS = Young Mania Rating Scale; HDRS = Hamilton Depression Rating Scale; Vit. = vitamin; CFU = colony-forming unit; L. = lactobacillus; B. = bifidobacterium; ↓ = improvement, IF-PEP = individual–family psychoeducational psychotherapy; AM = active monitoring; MADRS = Montgomery–Asberg Depression Rating Scale; DPA = n-3 docosapentaenoic acid; BD = Bipolar Disorder; hs-CRP = hs-C reactive protein; TNF = tumor necrosis factor.