Borderline Personality Disorder 

OBJECTIVE: The purpose of this study was to compare the efficacy of ethyl-eicosapentaenoic acid (E-EPA) and placebo in the treatment of female subjects with borderline personality disorder. METHOD: The authors conducted an 8-week, placebo-controlled, double-blind study of E-EPA in 30 female subjects meeting Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline personality disorder. RESULTS: Twenty subjects were randomly assigned to 1 g of E-EPA; 10 subjects were given placebo. Ninety percent of those in both groups completed all 8 weeks of the trial. Analyses that used random-effects regression modeling and controlled for baseline severity showed E-EPA to be superior to placebo in diminishing aggression as well as the severity of depressive symptoms. CONCLUSIONS: The results of this study suggest that E-EPA may be a safe and effective form of monotherapy for women with moderately severe borderline personality disorder.

Click here for further details.

E-EPA for bipolar depression

Ethyl-eicosapentanoic acid (ethyl-EPA) may be beneficial in the treatment of bipolar disorder (BD) and may have a neurotrophic/neuroprotective role in patients with neuropsychiatric disorders, the psychiatrists at the Institute of Psychiatry in London report. They have found ethyl-EPA (E-EPA) to be an effective and well-tolerated intervention for bipolar depression. Their studies were published in British Journal of Psychiatry and  in Journal of Psychopharmacology (Oxford). 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 Studies
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). 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 because 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), the 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- fatty 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 prescribed 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.
http://bjp.rcpsych.org/cgi/reprint/188/1/46

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.

The same team investigated further how E-EPA works in the brain of persons with bipolar disorder (BD). Fourteen female BD outpatients with moderate depressive symptoms were administered 2 g of ethyl-EPA per day or placebo for 12 weeks in a randomized, double-blind fashion. Quantitative, proton magnetic resonance spectroscopy imaging data were obtained prior to randomization and after 12 weeks of treatment from a single 12 ml volume of interest centred above the body of the corpus callosum (a region in the brain). A significant rise in brain levels of N-acetyl-aspartate (NAA), a putative marker of neuronal integrity, was observed in the E-EPA group but on in those on placebo. These results provide the first evidence for a probable neurotrophic role of ethyl-EPA treatment in BD underlining the need for more detailed investigation of its mechanism of action and therapeutic potential.
http://tinyurl.com/yjwlml

They conducted a 4-month, double-blind, placebo-controlled study, comparing ethyl estrificated omega-3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. A Kaplan-Meier survival analysis of the cohort found that the omega-3 fatty acid patient group had a significantly longer period of remission than the placebo group. In addition, for nearly every other outcome measure, the omega-3 fatty acid group performed better than the placebo group.

“Omega-3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder”, the authors stated in Archives of General Psychiatry.

http://archpsyc.ama-assn.org/cgi/content/abstract/56/5/407

Omega-3 increases the cell membrane fluidity
Dr Stoll´s team hypothesized that changes in brain membrane composition resulting from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity, as detected by reductions in T(2) values. In order to study this, they supplemented 12 women with bipolar disorder with omega-3 fatty acids for 4 weeks. They received either 1) high doses of omega-3 fatty acids for a total of 5.0–5.2 g/day of eicosapentaenoic acid (E-EPA), 3.0–3.4 g/day of docosahexanoic acid (DHA), and 1.7 g/day of other omega-3 fatty acids (N=6) or 2) low doses of omega-3 fatty acids for a total of 1.3 g/day of eicosapentaenoic acid and 0.7 g/day of docosahexanoic acid (N=6). A group of 9 bipolar subjects and a group 12 without bipolar disorder served as controls and they did not receive omega-3 fatty acids. T(2) values were acquired at baseline and after 4 weeks.

Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2). There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts.

“Omega-3 fatty acids lowered T(2) values, consistent with the hypothesis that the fluidity of cell membranes was altered. Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids, as reflected in T(2) values,” the authors conclude in American Journal of Psychiatry (2004).
http://ajp.psychiatryonline.org/cgi/content/full/161/10/1922

Another clinical trial using E-EPA in bipolar depression is currently ongoing
http://www.clinicaltrials.gov/ct/gui/show/NCT00096798