Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

Abstract

BackgroundDespite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal.ObjectivesTo conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies.MethodsA search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients.ResultsMeta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects.ConclusionsThe use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Ancillary treatments such as adjunctive eicosapentaenoic acid (EPA) (level 2),169, 279, 280 N ‐acetylcysteine (level 3),281 and light therapy (level 3),282 including bright light delivered midday (level 3),283 are also recommended as third‐line treatment options to use adjunctively to other medications. There may be additional benefits to using light therapy in combination with total sleep deprivation (level 2), although there is little clinical experience with this technique.…”

A review of nutrient treatments for paediatric depression

“…The antidepressant efficacy of omega-3 PUFAs on adults with major depressive disorder has been confirmed in several recent meta-analyses (Grosso et al, 2014b;Sublette et al, 2011). However, results are inconsistent and seem to be influenced by the preparation and dosage used (Bloch and Hannestad, 2012).…”

“…In particular, natural supplements such as St John's wort (Linde et al, 2005), S-adenosylmethionine (SAMe) (Papakostas, 2009), omega 3 polyunsaturated fatty acids (PUFAs) (Grosso et al, 2014b;Sublette et al, 2011) and zinc (Lai et al, 2012) have antidepressant benefits in adults. Investigations on the antidepressant effects of nutritional and herbal treatments for paediatric depression are less common, although have the potential to build upon current treatments.…”

There is No Association Between the Omega-3 Index and Depressive Symptoms in Patients With Heart Disease Who Are Low Fish Consumers

“…A meta-analysis of clinical trials of treatment with LCn3PUFAs for depression concluded that the use of these supplements is effective in patients with a diagnosis of Major Depressive Disorders (MDD) and in depressive patients without a diagnosis of MDD. [33] This study investigated associations of LCn3PUFA status, with (a) depression severity and (b) angina symptoms in patients with cardiac disease and depression who were low fish consumers. It was hypothesised that in patients with heart disease, LCn3PUFA status would be inversely associated with depression severity and angina symptoms.…”