Food and Behaviour Research

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Eicosapentaenoic acid in treatment-resistant depression.

Puri BK, Counsell SJ, Richardson AJ, Horrobin DF. (2002) Arch Gen Psychiatry 59(1) 91-2. 

Web URL: View this citation and related abstracts via PubMed here


Almost one-third of patients with depression fail to respond to existing treatments and new treatments are required. Epidemiological evidence about fish intake1 and blood levels of the relevant fatty acids2-4 suggest that increased intakes of n-3 fatty acids such as eicosapentaenoic acid (EPA) may be helpful. A mixture of EPA and docosahexaenoic acid (DHA) has been reported to improve depression and the course of illness in bipolar disorder5 but to date there are no reports of treatment of unipolar depression using this approach.

Case Report

We report the case of a 21-year-old male student with a seven-year history of unremitting depressive symptoms. At the age of 19 pharmacotherapy was commenced, owing to increasing illness severity with prominent low self-esteem, insomnia, sadness, inner tension, poor appetite, poor concentration, increasing social phobia, lethargy, pessimistic thoughts and suicidal thoughts. Over the following year there was no response to a variety of antidepressants, hypnotics and antipsychotic medication; indeed his condition continued to deteriorate. A two-month trial involving the addition of lithium carbonate to his antidepressant treatment was unsuccessful.

He was then referred to one of the authors (BKP). At this time he was actively suicidal although he had been taking paroxetine for 10 months. His symptoms met the DSM-IV criteria for Major Depressive Disorder, Recurrent. His score on the Montgomery and Åsberg Depression Rating Scale (MADRS) was 32. Owing to very good parental support it was decided not to admit the patient compulsorily to hospital, in spite of the severity of his illness and the very high suicide risk. He agreed to take pure ethyl-EPA at a dose of 4 g daily.

Ethyl-EPA led to a rapid improvement, including cessation of the previously unremitting severe suicidal ideation, within one month. Social phobia also improved dramatically. There was a progressive benefit and after nine months his symptoms had disappeared altogether, with a MADRS score of zero. Both he and his mother reported how different he had become. He no longer had any suicidal thoughts and was actively making plans for his future studies and career. The patient reported no side-effects of the medication. 


As the only change in therapy during the nine-month period was the addition of EPA, and since the patient’s depressive symptoms had previously continued to worsen, in spite of adequate trials with a range of standard medications, it seems likely that the clinical improvement was associated with the EPA. In view of the lack of effective drugs for treatment-resistant depression, double-blind placebo-controlled trials of EPA are indicated. 


  1. Hibbeln JR. Fish consumption and major depression. Lancet. 1998;351:1213.
  2. Peet M, Murphy B, Shay J, Horrobin D. Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients. Biol. Psychiatry. 1998;43:315-319.
  3. Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression. Lipids 1996;31:S157-S161.
  4. Maes M, Smith R, Christophe A, Cosyns P, Desnyder R, Meltzer H. Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20:4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affective Disord 1996;38:35-46.
  5. Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch. Gen. Psychiatry. 1999;56:407-412.

NB: A more detailed report of this case study was published separately, reporting on the changes observed in biochemical as well as clinical symptom measures following treatment with EPA.

For details of this report, please see:


Over the many years following this initial case report, numerous randomised controlled clinical trials have since confirmed that adjunctive treatment with long-chain omega-3 fatty acids can be of significant benefit to patients with clinical depression - and that EPA in particular appears to be responsible for these antidepressant effects.

In 2019, the world's leading research and clinical experts in this area published a consensus summary of the findings from research, along with practical, evidence-based guidelines for clinicians, free full text of which is available via open access. See: 

And for full lists of news articles and research studies in this area, which are regularly updated, see also: