Abstract

In depression there are low blood levels of omega-3 EFAs, including eicosapentaenoic acid (EPA). These fatty acids play important roles in signal transduction following activation of receptors for neurotransmitters and cytokines on neurons, glial cells and cerebrovascular cells. Between country and within country epidemiological studies show that omega-3 fatty acid consumption is inversely related to the national prevalence of depression and the risk of depression in individuals. Ethyl-EPA (E-EPA, LAX-101) is a pure single compound which is a candidate drug for depression treatment. Open label studies in severely depressed individuals who had failed to respond to standard antidepressants indicated that E-EPA was effective. A dose-ranging, placebo-controlled study of E-EPA at 1g, 2g or 4g/day was therefore performed in 70 patients who were depressed in spite of ongoing treatment with standard drugs. Patients were assessed at 4, 8 and 12 weeks on the Hamilton, Montgomery-Asberg and Beck scales for depression. 1g/d was the most effective dose with 69% of patients achieving a 50% reduction in Hamilton score as compared to 25% on placebo (p<0.001 for difference in change from baseline at 12 weeks). All of the individual items on all three rating scales were better on E-EPA than placebo indicating a broad spectrum effect (p<0.0004 for the Montgomery-Asberg and p<0.003 for the Beck). Similar results have been achieved in a placebo-controlled trial by RH Belmaker et al (Am J Psychiatry, in press). E-EPA offers a new approach to depression with none of the adverse effects of existing drugs.