Table 3.
Omega-3 fatty acid intake and its effects on depression: recent studies.
| Type of Depression | Type of Study | Participants | Intervention | Main Outcomes | Ref. |
|---|---|---|---|---|---|
| Major depressive disorder | Randomized, double-blind, placebo-controlled trial | Adolescents (12–19 years old), 51 participants | Intervention group: Capsules containing EPA + DHA in a 2:1 ratio taken for 10 weeks. Each participant started with an initial dose of 1.2 g/day. Doses were raised in increments of 0.6 g/day every 2 weeks (maximum possible dose of EPA + DHA was 3.6 g/day, i.e., 2.4 g/day + 1.2 g/day, respectively). Control group: Placebo capsules (corn and soybean oils) taken for 10 weeks. | Supplementation of omega-3 fatty acids was not superior to placebo in reducing depression severity as measured by the Children’s Depression Rating Scale-Revised or the Beck Depression Inventory-II. | [147] |
| Major depressive disorder | Randomized, double-blind, placebo-controlled clinical trial | Adults, 50 participants | All participants received sertraline (50–200 mg/day). Intervention group: 1 capsule containing 1000 mg of omega-3-polyunsaturated fatty acids taken for 12 weeks. Control group: 1 capsule containing placebo taken for 12 weeks. | Adjuvant treatment with omega-3 polyunsaturated fatty acids improved symptoms of depression (measured by the Beck Depression Inventory and Montgomery–Asberg Depression Rating Scale), sleep disturbances, anxiety, intolerance of uncertainty, regulation of emotions. | [148] |
| Major depressive disorder and chronic heart failure | Randomized, double-blind, placebo-controlled trial | Adults, 108 participants | Intervention groups: 1st group received 4 capsules/day of EPA/DHA at a dose of 500 mg per capsule (EPA/DHA ratio of 2:1) for 12 weeks; 2nd group received 4 capsules/day of almost pure EPA at a dose of 500 mg per capsule for 12 weeks. Control group: 4 capsules/day of placebo (corn oil) taken for 12 weeks. Patients not tolerating 4 capsules of the product took a reduced dose (1 capsule was the minimum dose which allowed to stay in the study). | Supplementation with EPA + DHA or EPA was effective in increasing levels of omega-3 fatty acids in erythrocytes, and the omega-3 index compared to placebo. However, no between-group differences in depression symptoms were observed when measured by the Hamilton Depression Scale and the Beck Depression Inventory-II. | [149] |
| Depression with overweight or obesity | Randomized, double-blind, controlled trial | Adult women, 45 participants | Intervention group: 6 capsules of omega-3/day (each capsule containing 180 mg of EPA + 120 mg of DHA) taken for 12 weeks. Control group: 6 capsules of placebo/day taken for 12 weeks. | Supplementation of omega-3 fatty acids significantly reduced depression versus placebo when measured by the Beck Depression Inventory. | [144] |
| Mild to moderate depression | Randomized, double-blind, controlled trial | Adults, 90 participants | All participants received psychoeducation. Intervention group: 15 capsules/day containing 300 mg of omega-3 fatty acids (i.e., 558 mg of DHA and 1064 mg of EPA/day) taken for 12 weeks. Control group: 15 capsules/day containing placebo taken for 12 weeks. | A combined intervention of omega-3 polyunsaturated fatty acids and psychoeducation can successfully ameliorate symptoms in people with mild to moderate depression when measured by the Beck Depression Inventory-II. However, the combination of omega-3 polyunsaturated fatty acids and psychoeducation was not better than the psychoeducation intervention alone. | [134] |
| Major depressive disorder | Randomized, double-blind, controlled trial | Adults, 88 participants | All participants took 4 identical capsules per day for 12 weeks. Each capsule contained either concentrated EPA (750 mg) or DHA (350 mg). Compared groups: 1st group took 4 capsules with EPA/day (3.0 g of EPA/day); 2nd group took 4 capsules with DHA/day (1.4 g of DHA/day); 3rd group took 2 capsules with EPA plus 2 capsules with DHA (1.5 g and 0.7 g of EPA and DHA/day, respectively). | Monotherapy with EPA or the combination of a higher dose of EPA and a lower dose of DHA resulted in a significantly higher remission rate than monotherapy with DHA, but no differences were observed between treatment with EPA versus EPA + DHA when measured by the Kaplan-Meier estimates of cumulative remission rates. Eicosapentaenoylethanolamide levels in plasma were positively correlated with rates of clinical remission. | [150] |
| Major depressive disorder with or at high risk for coronary heart disease | Randomized, double-blind, controlled trial | Adults, 144 participants | All patients received 50 mg/day of sertraline. Intervention group: 4 capsules with EPA/day (i.e., 2 g of EPA/day) for 10 weeks. Control group: 4 capsules of placebo (corn oil)/day for 10 weeks. | There were no differences between the groups in depression symptoms when measured by the Beck Depression Inventory II and the Hamilton Rating Scale for Depression. There were also no differences when compared the 10-week remission. | [151] |
| Depressive disorder or mixed anxiety and depressive disorder | Randomized, double-blind, controlled trial | Children (7–18 years old), 58 participants | All patients received standard antidepressant therapy. Intervention group: 20 mL of omega-3 fatty acid-rich fish oil emulsion (providing 2400 mg of total omega-3 fatty acids: 1000 mg of EPA and 750 mg of DHA, EPA:DHA ratio = 1.33:1) taken for 12 weeks. Control group: 20 mL of omega-6 fatty acid-rich sunflower oil emulsion taken for 12 weeks. | Improvement of symptoms measured by the Children’s Depression Inventory (CDI) accompanied by an increase in large HDL subfractions and reduction in small HDL subfractions in the group supplemented with omega-3 fatty acids was observed. A negative correlation between CDI score and HDL-cholesterol and the large HDL subfraction, but not LDL-cholesterol subfractions was detected. CDI score was not associated with erythrocyte membrane fluidity. | [152] |
| Major depressive disorder or depressive disorder not otherwise specified | Randomized, double-blind, controlled trial | Adolescents (9–21 years old), 42 participants | Intervention group: 3 capsules/day with fish oil taken for 12 weeks (1 capsule contains 450 mg of EPA, 40 mg DHA, and 260 mg of DHA; the total daily dose of EPA + DHA was 2130 mg; EPA/DHA ratio was 1.7:1). Control group: 3 capsules of placebo/day taken for 12 weeks. | Monotherapy with fish oil was not superior to placebo in reducing depressive symptoms in high-risk youths when measured by the Childhood Depression Rating Scale-Revised. | [153] |
| Major depressive disorder comorbid with cardiovascular diseases | Randomized, double-blind, controlled trial | Adults, 59 participants | Intervention group: omega-3 polyunsaturated fatty acids (2 g of EPA/day and 1 g of DHA/day) taken for 12 weeks. Control group: placebo taken for 12 weeks. | Omega-3 polyunsaturated fatty acids showed efficacy in improving core depression symptoms only in patients with severe major depressive disorder, measured by the Hamilton Depression Rating Scale. | [154] |
| Depressive disorder (n = 31) or mixed anxiety and depressive disorder (n = 29) | Randomized, double-blind, controlled trial | Children (7–18 years old), 60 participants | All participants received standard antidepressant therapy. Intervention group: omega-3 fish oil emulsion providing 2400 mg of total omega-3 fatty acids (1000 mg of EPA and 750 mg of DHA, EPA:DHA ratio = 1.33:1) taken for 12 weeks. Control group: omega-6 sunflower oil emulsion containing 2467 mg of omega-6 linoleic acid in triacylglycerol form taken for 12 weeks. | Significant reduction in CDI scores in the group receiving omega-3 fish oil emulsion when compared to the group receiving omega-6 fish oil emulsion. At the baseline, significantly lower concentrations of EPA and DHA levels as well as a higher omega-6/omega-3 ratio were detected in depressed patients. | [155] |
| Major depressive disorder | Randomized, double-blind, controlled trial | Adults, 61 participants | Intervention groups: 1st group took 1 g of EPA/day for 12 weeks; 2nd group took 2 g of EPA/day for 12 weeks; 3rd group took 4 g of EPA/day for 12 weeks. Control group: placebo taken for 12 weeks. | 4 g of EPA reduced depression symptoms measured by the Depressive Symptomatology, Clinician-Rated version. | [156] |
| Major depressive disorder | Randomized, double-blind, controlled trial | Adults, 45 participants | Intervention groups: EPA in the form of capsules containing approximately 590 mg of EPA and 152 mg of DHA. 1st group: 1 g of EPA/day taken for 12 weeks; 2nd group: 2 g of EPA/day taken for 12 weeks; 3rd group: 4 g of EPA/day taken for 12 weeks. Control group: placebo taken for 12 weeks. | EPA given at a dose of 4 g/day reduced clinical symptoms of depression, defined as achieving ≥50% reduction in the Inventory Depressive Symptomatology-30 scores. | [157] |
| Major depressive disorder or bipolar disorder | Randomized, double-blind, controlled, cross-over study | Adults, 42 participants | All patients received either antidepressant medications (SSRIs, desvenlafaxine, agomelatine, mirtazapine, vortioxetine) or medications for bipolar disorder (lithium, lamotrigine, clonazepam). Each capsule contained 130 mg of DHA and 35 mg of EPA. Patients received either 260 mg/day (2 capsules) or 520 mg/day (4 capsules) of DHA. | No change in residual symptoms of depression was detected, measured by the Hamilton Depression Rating Scale. | [158] |
| Major depressive disorder | Randomized, double-blind, controlled trial | Adolescents, young adults (15–25 years old), 233 participants | All participants were subjected to 50-min cognitive behavioral case management sessions every 2 weeks. Intervention group: 4 gelatin capsules with marine fish oil/day (providing 840 mg of EPA, 560 mg of DHA, and 5 mg of vitamin E) taken for 12 weeks. Control group: 4 gelatin capsules with paraffin oil taken for 12 weeks. | No significant effect of the fish oil treatment in major depressive disorder was observed when measured by the Quick Inventory of Depressive Symptomatology, Adolescent Version and the Montgomery–Åsberg Depression Rating Scale. Erythrocyte levels of polyunsaturated fatty acids were not associated with depression severity. | [159] |
| Depressive disorder | Randomized, open-label, controlled trial | Adolescents (12–13 years old), 71 participants | Intervention group: Paxil (paroxetine, 20 mg) + 3 capsules of omega-3-rich fish oil/day (providing 1941 mg of EPA + 759 mg of DHA; EPA:DHA ratio 2.56:1) taken for 12 weeks. Control group: Paxil (paroxetine, 20 mg)/day taken for 12 weeks. | Omega-3 fatty acids given with Paxil were more effective than Paxil alone in reducing depressive symptoms when measured by the Montgomery– Åsberg Depression Rating Scale. The combined treatment also improved cognitive function and memory better than monotherapy. | [160] |
| Major depressive disorder with or without high baseline high-sensitivity C-reactive protein | Match-mismatch trial, patients and raters were blind to baseline high-sensitivity C-reactive protein status | Adults, 101 participants | All subjects took their regular antidepressant drugs + 4 capsules of the study product/day (i.e., 2.2 g of EPA + 400 mg of DHA + 800 mg of other fatty acids + 10–24 mg of tocopherol-rich extracts) for 8 weeks. Subjects were allowed to take nutraceuticals other than omega-3 fatty acids (e.g., supplements with vitamins, zinc, or magnesium). | Omega-3 supplementation had a greater antidepressant effect in patients with moderately elevated high-sensitivity C-reactive protein compared to patients with lower high-sensitivity C-reactive protein when measured by the 17-item Hamilton Depression Rating Scale. | [161] |
CDI, Children’s Depression Inventory; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SSRI, selective serotonin reuptake inhibitor.