Omega-3 for Bipolar Disorder: Meta-Analyses of Use in Mania and Bipolar Depression
ABSTRACT 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 Clinical trial registries and gray literature (published or unpublished data not readily accessible via main databases) were also searched.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.
- SourceAvailable from: Con K K Stough
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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  . 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 . A meta-analysis by Martins  "
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.04/2015; 2(1). DOI:10.1016/j.aimed.2015.02.001
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- "On the other hand, convincing epidemiologic data associate diets high in omega-3 fatty acids with a lower risk of major depression , perinatal depression, and bipolar disorder (Noaghiul and Hibbeln, 2003; Hibbeln, 2009). Meta-analytic findings support the notion that the adjunctive use of omega-3 improves bipolar depressive symptoms (Simopoulos, 2002; Sarris et al., 2012). The BDNF/ TrkB signaling pathway is one of the neurobiological mechanisms that have been recently proposed to explain the mood regulating effects of n-3 PUFA in bipolar disorders (Balanza-Martinez et al., 2011). "
ABSTRACT: The exposure to adverse events early in life may affect brain development. Omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the development of mood and anxiety disorders. The aim of this study was to examine the interaction between variations in the early environment (handling or maternal separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on locomotor activity, sucrose preference, forced swimming test and on serum and hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups. Pups were removed from their dams (incubator at 32°C on postnatal days (PND) 1-10) during 10minutes/day (H) or 3hours/day (MS). On PND 35, males were subdivided into diets adequate or deficient in n-3 PUFA for 15weeks. H and MS gained weight differently, and animals receiving the n-3 PUFA deficient diet gained less weight. MS displayed a higher food consumption and higher consumption of sucrose solution during the secondhour of exposure to the sucrose preference test. No differences were observed in the swimming test. H group had increased locomotion and showed a higher response to amfepramone. No significant effect was observed on serum BDNF levels. BDNF protein levels were decreased in animals receiving the n-3 PUFA deficient diet. We observed that early life environment and a mild n-3 PUFA deficiency are able to affect several behavioral aspects (food and sucrose consumption and locomotor response), and lead to a differential hippocampal BDNF metabolism in adult life.Pharmacology Biochemistry and Behavior 03/2013; 107. DOI:10.1016/j.pbb.2013.03.006 · 2.82 Impact Factor
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- "Early studies (Chiu et al., 2003; Ranjekar et al., 2003) found that patients with bipolar disorder (BD) had lower erythrocyte membrane levels of n-3 FAs, but conflicting results have emerged from more recent studies (McNamara et al., 2010; Ross et al., 2011; Sublette et al., 2007). The efficacy of n-3 FA dietary supplementation as a treatment for mood disorders also remains equivocal (Gracious et al., 2010; Keck et al., 2006; Sarris et al., 2012). "
ABSTRACT: Epidemiological studies suggest that n-3 polyunsaturated fatty acid (n-3 FA) deficiency is a risk factor for bipolar disorders (BDs). The aim of this study was to determine whether such a deficit does exist in patients with BD and to characterize the overall plasma fatty acid (FA) profile in these patients. Using gas chromatography/mass spectrometry, we measured fasting plasma levels of 15 FAs in 42 patients diagnosed with BD according to DSM-IV criteria and in 57 age- and gender-matched healthy controls. Plasma docosahexaenoic acid (DHA) levels were significantly decreased in bipolar patients (p < 0.001 versus healthy controls). Compared with controls, patients had higher plasma levels of all other FAs, including arachidonic acid (AA, p < 0.001), alpha-linolenic acid (ALA, p < 0.001), and eicosapentaenoic acid (EPA) (p < 0.001). Although in the present study we observed significant DHA deficits in the plasma of bipolar patients our findings do not support the therapeutic use of ALA and/or EPA supplementation. DHA may provide a basis for possible pharmacological intervention in psychiatric disorders at the level of second messengers linked to the phosphatidylinositol cycle. Finally, measurement of FA levels in plasma seems to be more reliable and reproducible than assays of erythrocyte FA content.Journal of Psychiatric Research 11/2012; 47(3). DOI:10.1016/j.jpsychires.2012.11.004 · 4.09 Impact Factor