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: 5.14). 08/2011; 73(1):81-6. DOI: 10.4088/JCP.10r06710
Source: PubMed

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 Clinical trial registries and gray literature (published or unpublished data not readily accessible via main databases) were also searched.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.

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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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    • "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). "
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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). "
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