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Epidemiologic data suggest that people who consume diets rich in omega-3 fatty acids (FAs)—long-chain polyunsaturated FAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—have a decreased risk of major depressive disorder (MDD), postpartum depression, and bipolar disorder (BD).1-5 Omega-3 FA concentration may impact serotonin and dopamine transmission via effects on cell membrane fluidity.6 Therefore, decreased intake may increase the risk of several psychiatric disorders. As the average Western diet has changed over the last 2 centuries, omega-3 FA consumption has decreased.7 Omega-3 FAs cannot be synthesized by the body and must come from exogenous sources, such as fish and nuts. For a discussion of different types of dietary fats, see Box 1.8
Should we advise our patients to increase their omega-3 FA consumption? The American Psychiatric Association (APA) and the American Heart Association (AHA) recommend omega-3 FA consumption for the general population and in some cases, supplementation for specific disorders (Box 2).9-12 New data has been published since Current Psychiatry last reviewed the evidence for using omega-3 FAs for psychiatric conditions in 2004.8 This article looks at the latest evidence on the use of omega-3 FAs to treat mood disorders, schizophrenia, dementia, and other psychiatric conditions.
Dietary fat is saturated or unsaturated. Unsaturated fats are further categorized as monounsaturated or polyunsaturated (PUFA). PUFAs contain a hydrocarbon chain with ≥2 double bonds.8 The position of this double bond relative to the methyl end carbon—or “omega” carbon—groups the PUFAs into 2 categories:8
- omega-6 fatty acids, including arachidonic acid (AA) and linoleic acid (LA)
- omega-3 fatty acids, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA). ALA is a metabolic precursor to EPA and DHA.
PUFAs—in particular AA and DHA—are thought to contribute to cell membrane fluidity, modulation of neurotransmitters, and signal transduction pathways. As precursors to eicosanoids and cytokines, PUFAs may affect anti-inflammatory response systems.
Consumption of omega-3 fatty acids (FAs) reduces risk for arrhythmia, thrombosis, and atherosclerotic plaque, according to American Heart Association (AHA) guidelines. Omega-3 FA intake also may improve endothelial function, slightly lower blood pressure, and reduce inflammatory response. Replacing dietary saturated fat with polyunsaturated fat reduces coronary heart disease risk by 19%.9 The AHA recommends that all adults eat fish, particularly oily fish such as salmon or tuna, ≥2 times per week. Patients with documented coronary heart disease should consume 1 g/d eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) combined10 either via oily fish or omega-3 FA capsules. Side effects of omega-3 FA supplements are minor and include mild gastrointestinal discomfort, mostly burping or an unpleasant aftertaste; no cases of bleeding have been reported.11
For patients with hypertriglyceridemia, 2 to 4 g/d may be useful. Because of a theoretical risk of bleeding, doses >3 g/d should be supervised by a physician.
Because psychiatric illnesses and cardiovascular disease may be comorbid, the Omega-3 FA Subcommittee of the American Psychiatric Association supports the AHA’s guidelines regarding fish consumption, and further recommends that patients with mood, impulse control, or psychotic disorders consume ≥1 g/d of combined EPA and DHA.12
Limitations of the data
Reviewing the literature on omega-3 FAs to treat psychiatric disorders is hampered by several difficulties:13
- studies may evaluate the use of EPA alone, EPA combined with DHA, or DHA alone
- the doses of EPA and DHA and ratio of EPA to DHA of the supplements used in clinical trials varies greatly
- patients’ dietary consumption of omega-3 FAs is difficult to control
- DSM diagnostic criteria, as well as severity of illness, differ within studies.
In addition, studies may use omega-3 FAs as monotherapy or as adjuncts. All of these factors lead to difficulty interpreting the literature, as well as trouble in extracting data for meta-analysis.
Omega-3 FAs for mood disorders
MDD and other depressive diagnoses. Several meta-analyses examining the use of omega-3 FAs for treating depressive disorders have had equivocal findings. Variability in results might be partially explained by differences in the severity of baseline depression among diverse study populations, diagnostic variation, differing omega-3 supplementation protocols, or other issues.13 In addition, publication bias also may affect results.
In a 2011 literature review and meta-analysis of omega-3 FAs as monotherapy or an adjunct to antidepressants to treat MDD, Bloch and Hannestad6 concluded that omega-3 FAs offer a small but nonsignificant benefit in treating MDD. This review suggested that omega-3 FAs may be more effective in patients with more severe depression. The effects of varying levels of EPA vs DHA were not examined.