Table 2.
Randomized controlled trials and open trials of omega-3 PUFAs on affective symptoms.
| Study (Year) [Ref.] | Interventional Arm(s) | Comparison Arm(s) | Sample | Treatment Duration | Results |
|---|---|---|---|---|---|
| Pawelzcyk et al., 2018 [51] | EPA + DHA 2.2 g/day |
placebo | 71 patients at FEP | 26 weeks | ↑ level of telomerase in peripheral blood cells with ↓ depressive symptoms |
| Llorente et al., 2003 [79] | DHA 0.2 g/day monotherapy | Placebo | 99 healthy pregnant women |
16 weeks | no effect on postpartum depression |
| Marangell et al., 2003 [80] | add on to standard therapy DHA 2 g/day monotherapy | Standard therapy | 36 patients with MDD | 12 weeks | no significant differences |
| Silvers et al., 2005 [81] | EPA 0.6 g/day + DHA 2.4 g/day added to standard therapy |
Standard therapy | 77 patients with MDD | 12 weeks | no evidence that n-3PUFAs improved mood compared to placebo. Mood improved in both groups within the first 2 weeks of the study |
| Greyner et al., 2007 [82] | EPA 0.6 g/day + DHA 2.2 g/day add to standard therapy |
Standard therapy | 83 patients with MDD | 16 weeks | no significant differences |
| Hallahan et al., 2007 [134] | EPA (1.2 g/day) + DHA (0.9 g/day) | Placebo | 49 patients with self-harm behaviors (35 BPD) | 12 weeks | Improvement of depression, suicidality and reaction to daily stress |
| Freeman et al., 2008 [83] | EPA 1.1 g/day + DHA 0.8 g/day | placebo | 59 women | 8 weeks | no benefit on perinatal depressive symptoms |
| Jazayeri et al., 2008 [84] |
EPA 1 g/day | fluoxetine 20 mg/day | 60 patients with MDD | 8 weeks | ↓ depressive symptoms in both groups |
| Rees et al., 2008 [85] | ethyl-EPA 0.4 g/day + DHA 1.6 g/day | placebo | 26 pregnant patients | 6 weeks | no benefits on depressive symptoms |
| Rogers et al., 2008 [86] | EPA 0.63 g/day + DHA 0.85 g/day monotherapy |
placebo | 218 mild to moderate depressed patients untreated | 12 weeks | n-3PUFAs not have beneficial or harmful effects on mood in mild to moderate depression. |
| Doornbos et al., 2009 [87] | DHA 0.22 g/day or DHA 0.22 g/day + AA (0.22 g/day arachidonic acid) monotherapy |
placebo | 119 healthy pregnant women | 28 weeks | red blood cell DHA, AA and DHA/AA ratio did not correlate with EPDS or blues scores |
| Lucas et al., 2009 [88] | EPA 1.05 g/day + DHA 0.25 g/day mono-therapy |
placebo | 120 patients with psychological distress with or without MDD in comorbidity |
8 weeks | no significant differences |
| Makrides et al., 2010 [89] | DHA-rich tuna oil capsules 0.5 g/day monotherapy |
placebo | 2399 healthy pregnant women at 21 weeks’ gestation |
women received assigned capsules daily, from study entry until birth of their child | DHA during pregnancy did not lower levels of postpartum depression |
| Antypa et al., 2012 [90] | EPA 1.74 g/day+ DHA 0.25 g/day added to standard therapy |
Standard therapy | 71 patients with history of at least one MDD | 4 weeks | no significant effects on memory, attention, cognitive reactivity and depressive symptoms |
| Mozurkewich et al., 2013 [91] | EPA 1.06 g/day+ DHA 0.27 g/day monotherapy | EPA 0.18 g/day + DHA 0.9 g/day monotherapy |
126 healthy pregnant women | 6–8 weeks | no differences between groups in BDI scores or other depression endpoints |
| Mischoulon et al., 2009 [92] | EPA 1 g/day + (+ 0.2% dL alphatocopherol) monotherapy |
placebo | 57 patients with MDD | 8 weeks | ↓ depressive symptoms assessed with HDRS, but no statistical significance |
| Park et al., 2015 [93] | EPA 1140 g/day + DHA 0.6 g/day add to standard therapy | Standard therapy | 35 patients with MDD | 12 weeks | no significant differences |
| Young et al., 2017 [94] | PEP + EPA 1.4 g/day + DHA 0.2 g/day + 0.4 g/day other | placebo | 72 depressed patients 7–14 years old | 12 weeks | ↓ co-occurring behavior symptoms in youth with depression. |
| Gabbay et al., 2018 [95] | 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 EPA 2.4 g + DHA 1.2 g) |
placebo | 51 psychotropic medication-free adolescents with MDD aged 12–19 years old | 10 weeks | n-3PUFAs do not appear to be superior to placebo. |
| Tayama et al., 2019 [96] | DHA 500 mg/day + EPA 1000 mg/day | placebo | 20 patients with mild-to-moderate depression | 12 weeks | no significant differences |
| Nemets et al., 2006 [97] | ethyl-EPA 0.4 g/day + DHA 0.2 g/day | placebo | 20 patients 6–12 years-old | 16 weeks | ↓ depressive symptoms measured with CDRS, CDI and CGI |
| Peet & Horrobin 2002 [98] | Ethyl-EPA 1/2/4 g/day + Standard therapy | Placebo + Standard therapy | 70 patients with persistent depression despite ongoing treatment | 12 weeks | Ethyl-EPA 1 g/day group > placebo group no significant differences in the Ethyl-EPA 2 and 4 g/day groups |
| Su et al., 2003 [99] | ethyl-EPA 4.4 g/day + DHA 2.2 g/day add-on existing antidepressant treatment |
Placebo + existing antidepressant treatment |
22 patients with MDD | 8 weeks | ↓ depressive symptoms measured with HDRS |
| Nemets et al., 2006 [100] | ethyl-EPA 0.4 g/day + DHA 0.2 g/day |
Placebo | 20 depressed patients 6–12 years-old | 16 weeks | ↓ depressive symptoms measured with CDRS, CDI and CGI |
| Mischoulon et al. (2009) [101] | EPA 1 g/day + (+0.2% dL alphatocopherol) monotherapy |
Placebo | 57 MDD patients | 8 weeks | ↓ depressive symptoms assessed with HDRS, but no statistical significance |
| Rondanelli et al., 2010,2011 [102,103] | EPA 1.67 g/day + DHA 0.83 g/day added to existing antidepressant treatment | Placebo + existing antidepressant treatment |
46 elderly female residents in a nursing home |
8 weeks | ↓ depressive symptoms assessed with GDS, improvement of phospholipids fatty acids profile |
| Lespérance et al., 2011 [104] |
EPA 1.05 g/day + DHA 0.15 g/day + existing antidepressant treatment |
Placebo + existing antidepressant treatment | 432 patients with a major depressive episode | 8 weeks | ↓ depressive symptoms only for patients without comorbid anxiety disorders |
| Tajalizadekhoob et al., 2011 [105] | EPA 0.18 g/day + DHA 0.12 g/day add to standard therapy (55 patients) or in monotherapy (11 patients) |
Placebo | 66 patients with mild-to moderate depression aged > 66 years | 24 weeks | low-dose n-3PUFAs have some efficacy in mild to moderate depression |
| Gertsik et al., 2012 [106] | EPA 0.9 g/day + DHA 0.2 g/day + other n-3 PUFAs (0.1 g/day) added to citalopram |
Placebo added to citalopram | 42 MDD patients taking citalopram | 9 weeks | significantly greater improvement in HDRS scores |
| Krawczyk et al., 2012 [107] | EPA 2.2 g/day + DHA 0.7 g/day + GLA (0.24 g/day) + vit. E added to standard therapy |
Standard therapy | 21 patients with severe episode of treatment resistant recurring depression | 8 weeks | n-3PUFAs significantly improved HDRS scores |
| Rizzo et al., 2012 [108] |
EPA/DHA 2.1/2.5 g of n3-PUFA monotherapy |
Placebo | 46 MMD patients (only women > 66 years old) | 8 weeks | mean GDS score and AA/EPA ratio, in whole blood and RBC membrane phospholipids, were significantly lower |
| Mozaffari-Khosravi et al., 2012 [109] |
EPA 1 g/day or DHA 1 g/day added to standard therapy |
Placebo + Standard therapy | 81 mild to moderate depressed patients |
12 weeks | ↓ HDRS score EPA > compared with those in the DHA or placebo groups |
| Judge et al., 2014 [110] |
DHA 0.3 g/day | Placebo | 42 healthy pregnant women |
8 weeks | ↓ depressive symptoms assessed with PDSS |
| Ginty et al., 2015 [111] |
EPA + DHA 1.4 g/day monotherapy | Placebo | 23 depressed patients | 3 weeks | n-3PUFAs group had a significant reduction in BDI scores over time |
| Jahangard et al., 2018 [112] |
n-3 PUFAs (1000 mg/day) + sertraline (50–200 mg/day) |
sertraline (50–200 mg/day) |
50 MDD outpatients | 12 weeks | ↓ depression, anxiety, sleep and patients’ competencies to regulate their emotions. |
| Chiu et al., 2005 [113] |
4.4 g/day EPA + 2.4 g/day DHA added on valproate 2 g/day |
valproate 2 g/day and | 16 newly hospitalized patients in the acute manic phase of bipolar disorder |
4 weeks | No significant differences |
| Hirashima et al., 2004 [115] |
High dose: EPA, 5.0–5.2 g/day; DHA, 3.0–3.4 g/day; other, 0.3–1.7 g/day + standard therapy |
Standard therapy | 21 patients with bipolar disorder | 4 weeks | No significant differences |
| Keck et al., 2006 [116] |
EPA 6 g/day in addition to at least one mood stabilizer |
at least one mood stabilizer |
121 patients with bipolar depression or rapid cycling bipolar disorder |
4 months | No significant differences |
| Frangou et al., 2006 [117] |
ethyl-EPA 1 or 2 g/day added to stable psychotropic medications |
stable psychotropic medications | 75 patients with bipolar disorder | 12 weeks | ↓ depressive symptoms measured with HDRS |
| Murphy et al., 2012 [118] |
omega-3 fatty acids plus cytidine or omega-3 fatty acid plus placebo in addition to a mood stabilizer |
only placebo in addition to a mood stabilizer |
45 patients with type I bipolar disorder |
4 months | no benefits of omega-3 fatty acids on affective symptoms |
| Stoll et al., 1999 [119] |
EPA 6.2 g/day + DHA 3.4 g/day | Placebo | 30 patients with bipolar disorder | 16 weeks | ↓ depressive symptoms measured with HDRS |
| Gracious et al., 2010 [120] |
ALA in addition to psychotropic medication |
Standard therapy | children and adolescent with bipolar I or II disorder |
16 weeks | significant improvement of overall symptom severity compared with placebo |
| Zanarini & Franknburg, 2003 [133] |
Ethyl-EPA 1 g/day (with no standard psychiatric therapies) |
placebo | 30 females with BPD | 8 weeks | ↓ depression |
| Buydens-Branchey et al., 2006, 2008 [130,131] |
eicosapentaenoic acid + docosahexaenoic acid 3 g/day | Placebo | 44 patients with anxiety disorder and substance abuse disorder | 3 months + 3 months after therapy discontinuation | ↓ anxiety symptoms > in PUFAs group than in placebo one, also after therapy discontinuation |