EPA Found Beneficial Treatment for Bi-polar Disorder
Psychiatrists at the Institute of Psychiatry in London report that ethyl-EPA (E-EPA) appears to be an effective and well-tolerated intervention for bipolar depression. Their study was published in British Journal of Psychiatry. These results confirm initial reports from Harvard University (USA), Sheffield University (UK) and Ben Gurion University (Israel).
Bipolar disorder is a recurring, often chronic, illness characterised by periods of mania and depression with variable inter-episode recovery. For the majority of patients it is the depressive component of this illness that contributes to most of the associated morbidity, social disability and mortality. Research and clinical experience suggest that acute treatment and prevention of depressive episodes is by far the most challenging aspect of the care of patients with the disorder. Interest has grown in the potential role of omega-3 fatty acids such as EPA in bipolar depression following the first report by Professor Stoll´s team at from Harvard University in 1999. This and other studies suggest that E-EPA may prolong inter-episode remission in people with bipolar disorder.
British Study
A team of psychiatrists lead by Dr Sophia Frangou from the Institute of Psychiatry in London sought to investigate the benefits further by examining the efficacy of ethyl-EPA as an adjunctive therapy in 75 out-patients with bipolar depression (type I or II).
Sophia Frangou is Reader in Psychiatry and Head of the Section of Neurobiology of Psychosis at the Institute of Psychiatry, London, UK and Honorary Consultant Psychiatrist for the South London and Maudsley NHS Trust. She qualified from the University of Athens, Greece, trained in Psychiatry at the Maudsley Hospital and obtained a masters degree in neuroscience and later a doctoral degree from the University of London. Her research focuses on pathophysiological processes in psychosis using clinical, cognitive and neuroimaging techniques.
The participants, males and females, between the ages of 18 and 70 years, were randomly assigned to receive adjunctive treatment with 1 g/day of E-EPA (n=24), 2 g/day of E-EPA (n=25) or placebo (n=26) for 12 weeks. The decision to test two different doses of E-EPA was based on previous studies that had found 2 g/day optimal for schizophrenia and 1 g/day for uniopolar depression. Adherence to study medication was monitored by pill-counting.
A prerequisite for eligibility was at least score 10 on the 17-item Hamilton depression test score (HRSD). The efficacy of the supplementation was assessed at the base line, 4 and 12 weeks, using the following tests:
Hamilton Rating Scale for Depression, primary outcome
Young Mania Rating Scale (secondary outcome)
Clinical Global Impression Scale (CGI) (secondary outcome)
The HRSD scores fell in the 1g/d and 2g/d E-EPA groups from 14,7 and 14,8 to 9,1 and 9,9, respectively, and in the placebo group from 15,4 to 13,5. The corresponding changes in he YMRS scores were from 6,7 to 6,6; 4,7 to 7,2; and 6,3 to 9,9. The average score on the Clinical Global Impression scale after 12 weeks of treatment was 0.7 points lower among patients receiving E-EPA than among those given placebo (3,1 vs 2,4 and 2,3). Overall, there was no superior benefit in taking 2 g of E-EPA compared with taking 1 g of the fatty acid. The authors emphasize that about half of those in the placebo group had their medication adjusted during the supplementation bacause their symptoms persisted or worsened.
E-EPA was generally well tolerated. Loose stools and gastrointestinal discomfort were the most common side effects, but there were no significant differences among the groups in the presence of these adverse effects. Moreover, treatment with E-EPA had minimal propensity to induce mania, the researchers note.
The authors elaborate on the mechanisms of E-EPA actions in the nervous system. They suggest that E-EPA may exert its effects by binding to receptors, leading to the release of second messenger molecules that initiate a cascade of biochemical changes, ultimately resulting in an altered state of the neuron. Mood stabilising drugs appear primarily to affect second messenger systems, E-EPA may be similar to mood stabilizers in this respect, the authors propose. It is possible that the incorporation of EPA into cell membranes inhibits the action of phospholipase A2, an enzyme that is important for the production of second messenger molecules such as arachidonic acid (AA), or it may directly inhibit “downstream” signalling molecules such as protein kinase C (PKC), theu auhors write.
“This is the firsts randomized double-blind placebo-controlled clinical trial of ethyl-EPA in depression in people with bipolar depression. Our results confirm initial observations of the antidepressant effect of omega-3- faty acids, particularly of ethyl-EPA. They also strongly suggest that treatment with ethyl-EPA is not associated with increased risk inducing manic symptoms. At the doses precribed here the side-effects were minimal and indistinguishable from those in the placebo group. Although the role of ethyl-EPA in the treatment of bipolar disorder requires further evaluation, our results offer optimism that ethyl-EPA represents a new generation of naturally occurring and safe psychotropic compounds”, the team acknowledges.
They add that, as ethyl-EPA is a naturally occurring compound, it may prove more acceptable to patients than other pharmacological interventions.
SOURCE: British Journal of Psychiatry
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