Omega-3 for Bipolar Disorder: Meta-Analyses of Use in Mania and Bipolar Depression

Department of Psychiatry, Faculty of Medicine, The University of Melbourne, Richmond, Victoria, Australia.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 08/2011; 73(1):81-6. DOI: 10.4088/JCP.10r06710
Source: PubMed


Studies using augmentation of pharmacotherapies with omega-3 in bipolar disorder have been conducted; however, to date a specific meta-analysis in this area has not been published. Thus, we present the significant findings from meta-analyses of omega-3 in the treatment of bipolar depression and bipolar mania.
PubMed, CINAHL, Web of Science, and Cochrane Library databases were searched for clinical trials up to September 1, 2010, using the search terms bipolar disorder OR bipolar depression OR bipolar mania OR mania OR hypomania OR cyclothymia with the search terms omega 3 OR essential fatty acids OR polyunsaturated fatty acids OR DHA OR EPA OR fish oil OR flax oil. Clinical trial registries and gray literature (published or unpublished data not readily accessible via main databases) were also searched.
The analysis included randomized controlled studies 4 weeks or longer, with a sample size > 10, written in English, using omega-3 for diagnosed bipolar depression or mania. No criteria were set for age, gender, or ethnicity.
A random-effects model was used. The model analyzed the standard mean difference between treatment and placebo between baseline and endpoint, combining the effect size (Hedges g) data. Funnel plot and heterogeneity analyses (I²) were also performed.
The findings of 5 pooled datasets (n = 291) on the outcome of bipolar depression revealed a significant effect in favor of omega-3 (P = .029), with a moderate effect size of 0.34. On the outcome of mania, 5 pooled datasets (n = 291) revealed a nonsignificant effect in favor of omega-3 (P = .099), with an effect size of 0.20. Minor heterogeneity between studies on the outcome of bipolar depression was found (I² = 30%; P = .213), which was not present on the outcome of bipolar mania (I² = 0%; P = .98). Funnel plot symmetry suggested no significant likelihood of publication bias. Meta-regression analysis between sample size and effect size, however, revealed that studies with smaller sample sizes had larger effect sizes (P = .05).
The meta-analytic findings provide strong evidence that bipolar depressive symptoms may be improved by adjunctive use of omega-3. The evidence, however, does not support its adjunctive use in attenuating mania.

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    • "In conclusion, Omega-3 and -6 PUFAs are molecular modulators of neurotransmission and inflammation. Some evidence indicates that eicosapentaenoic acid (EPA) is the active n-3 PUFA responsible for moodaltering effects in n-3 PUFA supplementation studies of depression (Sublette et al. 2011; Sarris et al. 2012). Lower n-3 PUFAs have been seen in a number of clinical studies of BD, particularly in erythrocyte studies (McNamara et al. 2010). "

    Full-text · Dataset · Feb 2016
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    • "" Treatment outcomes of omega-3 PUFAs in Ness's study were negative and contributed greatly to the pooled estimate in Appleton's meta-analysis. Despite the uneven quality of published studies, recent metaanalytic evidence strongly supports the adjunctive use of omega-3 to treat bipolar depression [29]. However, studies regarding the effectiveness of omega-3 PUFAs in the acute manic phase of bipolar disorder are still lacking. "
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    ABSTRACT: The unmet need of current pharmacotherapy and the high occurrence of somatic symptoms and physical illness in depression imply that the 'monoamine hypothesis' is insufficient in approaching the aetiology of depression. Clinically, depressed patients manifest higher levels of inflammatory biomarkers, while proinflammatory cytokines induce neuropsychiatric symptoms (sickness behaviour) as well as major depressive episodes. Indeed, accumulating evidence suggests that inflammation dysregulation plays an important role in the pathophysiology of depression. Biological mechanisms that link inflammation to neuropsychiatric symptoms are vital in the understanding of the "mind-body" interface. IFN-α-induced depression is the most powerful support for the inflammation theory of depression. This clinical observation provides an excellent model for depression research. By comparing subjects with and without major depression induced by the cytokine treatment, statistical powers could be largely increased by reducing phenotypic variation (homogeneity in aetiological factors). In addition, the anti-inflammatory pathway has recently become an important topic in looking for new antidepressant therapies. For example, anti-inflammatory compounds, omega-3 polyunsaturated fatty acids (omega-3 PUFAs or n-3 PUFAs), have been found to be associated with the development and treatment for depression in human and animal models. Here I review recent epidemiological studies, cross-sectional and longitudinal case-controlled studies, interventional clinical trials, as well as basic animal and cellular studies to prove the linkage among omega-3 PUFAs, inflammation, and depression.
    Full-text · Article · Nov 2015
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    • "fatty acids have a critical role in neural function and great potential for treating depression, especially if an inflammatory causation is present [17] [18]. The antidepressant activity of omega-3 fatty acids appears to occur via modulation of norepinephrine , dopamine and serotonin re-uptake, degradation, synthesis and receptor binding; anti-inflammatory effects; and the enhancement of cell membrane fluidity [19]. A meta-analysis by Martins [20] "
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    ABSTRACT: Current treatment for major depressive disorder (MDD), a prevalent and disabling mental illness, is inadequate, with two-thirds of people treated with first-line antidepressants not achieving remission. MDD is for many a chronic condition, often requiring multiple treatment attempts, thus development of additional interventions is urgently required. An emerging approach to improve non-response to antidepressants is the use of adjunctive nutraceuticals. The pathophysiology of MDD is considered to involve a range of abnormalities (monoamine impairment, neuro-endocrinological changes, reduced brain-derived neurotrophic factor, and cytokine alterations). By targeting an array of these key neurobiological pathways via specific nutraceuticals (S-adenosyl methionine; [SAMe], 5-HTP [active tryptophan], folinic acid [active folic acid], omega-3 fatty acids, and zinc), there is the potential to provide a more comprehensive therapeutic biological approach to treat depression. We are currently conducting a National Health and Medical Research Council funded study in Australia (APP1048222). The clinical trial is phase II/III, multi-site, 3-arm, 8-week, randomised, double-blind, placebo-controlled study using SAMe + folinic acid versus a combination nutraceutical (SAMe, 5-HTP, folinic acid, omega-3, and zinc) or matching placebo in 300 currently depressed participants with diagnosed MDD who are non-responsive to current antidepressants (ANZCTR, protocol number: 12613001300763). The results may provide evidence for a novel adjunctive neurobiological approach for treating depression.
    Full-text · Article · Apr 2015
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