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Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover.

Puri BK, Counsell SJ, Hamilton G, Richardson AJ, Horrobin DF. (2001) International Journal of Clinical Practice. 55(8) 560-3. 

Web URL: View this and related abstracts via PubMed here


The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine months later.

The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically.

During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover.

Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.


Before enrolling in this detailed single-case study, the young man who took part had been experiencing severe and unrelenting depressive symptoms for one third of his life, since he was 21 at the time, and their onset began when he was only 14 years of age.

Over the previous 2 years of his illness, he had been treated with various different pharmaceutical medications (including antidepressants, hypnotics, antipsychotics and a brief trial of lithium carbonate), none of which had helped him to any meaningful degree. 

At the start of this pilot study of EPA treatment, he had already been actively suicidal for some time.  However, as he had very good parental support, he remain unhospitalised during the 9 months of treatment with pure EPA (at a dosage of 4g/day, and as an adjunct to his current antidepressant medication).

Within the first month, there was a dramatic improvement in his mood and other symptoms - which had included severe social anxiety and withdrawal, as well as insomnia.  This improvement continued over the following nine months, by which time he not only no longer met criteria for clinical depression, but was effectively symptom-free.

A brief summary of the clinical improvement in depressive symptoms in this patient following EPA treatment is reported elsewhere:

The current study provides additional details of experimental measures carried out at baseline, and after 9 months of supplementation with EPA, which were all consistent with the proposal that changes in fatty acid metabolism were more likely to account for this marked clinical improvement than a spontaneous placebo response. These included:

  • Improved skin flushing response to niacin (an index of fatty acid metabolism and omega-6 AA status) - which increased by 30% over the study period.
  • Marked improvements in brain membrane phospholipid turnover, as indicated by brain imaging using 31-phosphorus MRS
  • Increased brain volume, as indexed by structural MRI scans showing reductions in lateral ventricular volume.


We are pleased to report that 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: