Omega-3 fatty acids and unipolar major depression

Abstract

Fatty acids (FAs) are either satu rated FAs (solid at room tempera ture) or unsaturated FAs (liquid at room temperature). Polyunsaturated fats are further defined by the location of the first double bond; omega-6 FA double bonds begin at the sixth carbon atom, while omega-3 FA double bonds begin at the third carbon atom. Omega-6 FAs include linoleic acid, gamma-linolenic acid, and arachadonic acid. Omega-3 FAs include plant-derived alpha-linolenic acid (ALA) and marine-derived, long-chain eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA). Neuronal membrane fluidity depends on which FAs are incorporated into the cell membrane. DHA and EPA are incorporated into neuronal cell membranes and allow the membrane to be fluid or flexible. Such membrane fluidity is necessary for proper functioning of lipid messengers that signal cascades that can cause changes in neuronal flexibility and function. Membrane fluidity is important in psychiatric illnesses because serotonin and catecholamine receptors, ion channels, transporters, and G protein-coupled receptors depend on fluid or flexible cell membranes for proper functioning. When a person is deficient in omega-3 FAs, omega-6 FAs are incorporated more into cell membranes, leading to stiffer, less flexible cell membranes. Thus, the ratio of omega-6 to omega-3 FAs and the total level of omega-3 FAs are essential for normal neuronal functioning. This article is first in a two-part series on omega-3 FAs and psychiatric illnesses. Depression affects 21 million Americans. Women are twice as likely as men to experience depression during their lifetime. Depressive symptoms commonly include depressed mood, loss of interest in pleasurable activities, changes in sleep and weight, difficulty concentrating, and thoughts of suicide. While prescription drugs are effective for depression, some patients have residual symptoms, while others choose OTC drugs in place of prescription antidepressants. Interest in omega-3 FA supplementation has grown out of epidemiologic studies indicating that countries with high fish consumption have lower rates of depression. Studies also suggest that the incidence of depression is increasing as our diet shifts from a 2:1 ratio to a 10:1 ratio of omega-6:omega-3 FA intake. Observational studies suggest a link between omega-3 FA concentrations in the body and incidence or severity of depression. Other studies indicate that eating seafood twice weekly may decrease the risk of depression and suicidal thoughts. Still other studies indicate that a 1:1 or 2:1 ratio of omega- 6: omega-3 FA concentrations in the blood decreases the risk of depression. Such findings have not been supported in clinical trials. A recent meta- analysis of 28 studies reported that omega-3 FA supplementation was not effective for treatment or prevention of depression. Further analysis revealed that studies using supplements with more than 50% or pure EPA showed a significant reduction in depressive symptoms. Some methodological issues have called these results into question, however; for example, the most rigorously designed trials and those with large sample size were less likely to find omega-3 FA supplementation effective in depression. Although observational studies are generally positive, results from clinical trials are inconsistent. The mixed results are caused by differences in study design such as type of depression studied (e.g., unipolar vs. postpartum), phase of treatment (e.g., acute vs. preventive), type of treatment (e.g., monotherapy vs. augmentation), type of supplementation (e.g., DHA, EPA, ALA, omega-6), and dosage. At this point, it is difficult to draw conclusions about the efficacy of omega-3 FA supplementation in the prevention or treatment of unipolar major depression. Patients should be counseled that omega-3 FAs have not consistently been shown to be effective for depression. Given a benign safety profile and benefits in cardiac disease, however, omega-3 FA supplementation is a reasonable option to treat mild depressive symptoms or to augment ongoing psychotherapy or antidepressant treatment. It is also reasonable for patients to strive for an omega- 6:omega-3 FA intake ratio of less than 10:1. Patients experiencing significant signs of depression or suicidal thoughts should be referred to their primary care clinician, a psychiatrist, or an emergency department, depending on the urgency and severity of symptoms. Patients without a history of depression wishing to prevent future depressive symptoms can be encouraged to eat a variety of fish— preferably oily fish such as salmon—two or more times weekly. Patients with a history of depression or active depression should be encouraged to consume 1 g daily of EPA plus DHA through ingestion of fish or supplements, if drug interactions or contraindications do not exist.CONTRIBUTING EDITORAnne L. Hume, PharmD, FccP, BcPS, is Professor of Pharmacy at the University of Rhode Island. She is also a complementary and alternative medicine editor for APhA's Handbook of Nonprescription Drugs. Anne L. Hume, PharmD, FccP, BcPS, is Professor of Pharmacy at the University of Rhode Island. She is also a complementary and alternative medicine editor for APhA's Handbook of Nonprescription Drugs.