Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder.

Psychopharmacology Research Program, Department of Psychiatry, University of Cincinnati College of Medicine and the Mental Health Care Line, Cincinnati, Ohio 45267-0559, USA.
Biological Psychiatry (Impact Factor: 9.47). 12/2006; 60(9):1020-2. DOI: 10.1016/j.biopsych.2006.03.056
Source: PubMed

ABSTRACT The results of pilot trials suggest that omega-3 fatty acids may have efficacy in the treatment of mood symptoms in bipolar disorder.
We conducted a 4-month, randomized, placebo-controlled, adjunctive trial of ethyl-eicosapentanoate (EPA) 6 g/day in the treatment of bipolar depression and rapid cycling bipolar disorder. Subjects were receiving mood-stabilizing medications at therapeutic doses or plasma concentrations. The measures of efficacy were early study discontinuation, changes from baseline in depressive symptoms (Inventory for Depressive Symptomology total score) and in manic symptoms (Young Mania Rating Scale total score), and manic exacerbations ("switches"). We also measured side effects and bleeding time, a biomarker of drug action.
Overall, there were no significant differences on any outcome measure between the EPA and placebo groups.
This study did not find overall evidence of efficacy for adjunctive treatment with EPA 6 g/day in outpatients with bipolar depression or rapid cycling bipolar disorder.

Download full-text


Available from: Susan L Mcelroy, Jul 02, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological and controlled intervention trials suggest that omega-3 (n-3) fatty acid deficiency represents a reversible risk factor for recurrent affective disorders. However, there is limited comparative information available regarding the n-3 fatty acid status and associated mood symptoms in medication-free patients with major depressive disorder (MDD) and bipolar disorder (BD). The fatty acid composition of erythrocyte membranes from adult male and female healthy controls (n=20) and medication-free patients with MDD (n=20) and BD (n=20) was determined by gas chromatography. Associations with depression and mania symptom severity scores were investigated. After correction for multiple comparisons, both MDD (-20%) and BD (-32%) patients exhibited significantly lower erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition relative to healthy controls, and there was a trend for lower DHA in BD patients relative to MDD patients (-15%, p=0.09). There were no gender differences for DHA in any group. Other n-3 fatty acids, including eicosapentaenoic acid (EPA, 20:5n-3) and docosapentanoic acid (22:5n-3), and n-6 fatty acids, including arachidonic acid (AA, 20:4n-6), were not different. Erythrocyte DHA composition was inversely correlated with indices of delta-9 desaturase activity (18:1/18:0), and associated elevations in oleic acid (18:1n-9) composition, and delta-6 desaturase activity (20:3/18:2). DHA composition was not significantly correlated with depression or mania symptom severity scores. Data regarding diet and life style factors (cigarette smoking) were not available to evaluate their contribution to the present findings. Male and female patients with MDD and BD exhibit selective erythrocyte DHA deficits relative to healthy controls, and this deficit was numerically greater in BD patients. Selective DHA deficits are consistent with impaired peroxisome function, which has implications for n-3 fatty acid interventions aimed at preventing or reversing this deficit.
    Journal of Affective Disorders 10/2010; 126(1-2):303-11. DOI:10.1016/j.jad.2010.03.015 · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: These guidelines are based on a first edition that was published in 2002, and have been edited and updated with the available scientific evidence until September 2009. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute bipolar depression in adults. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from the clinical trial database, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into six levels of evidence (A-F). As these guidelines are intended for clinical use, the scientific evidence was finally assigned different grades of recommendation to ensure practicability. We identified 10 pharmacological monotherapies or combination treatments with at least limited positive evidence for efficacy in bipolar depression, several of them still experimental and backed up only by a single study. Only one medication was considered to be sufficiently studied to merit full positive evidence. Although major advances have been made since the first edition of this guideline in 2002, there are many areas which still need more intense research to optimize treatment. The majority of treatment recommendations is still based on limited data and leaves considerable areas of uncertainty.
    The World Journal of Biological Psychiatry 02/2010; 11(2):81-109. DOI:10.3109/15622970903555881 · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Reduced concentrations of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) have been reported in the postmortem bipolar disorder (BD) brain. Additionally, an increased prevalence of BD has been related to low dietary intake of fish, and dietary supplements containing fish products or DHA have been reported to ameliorate BD symptoms. These observations suggest that brain lipid metabolism, particularly involving DHA, is disturbed in BD. To test this suggestion, concentrations of different lipids were measured using internal standards in postmortem frontal cortex from eight BD patients and six matched controls. Compared with control cortex, the BD cortex showed no statistically significant difference in mean concentrations (per gram wet weight) of "stable" lipids (total lipid, total phospholipid, individual phospholipids, or cholesterol), of unesterified fatty acids, or of esterified DHA or AA within stable lipids. Fractional esterified AA and DHA concentrations also did not differ significantly between groups. Some fatty acid concentration differences were found in low-abundant cholesteryl ester. These results do not support the hypothesis of disturbed brain lipid concentrations, including concentrations of AA and DHA, in BD. Positron emission tomography might be used, however, to see if brain AA or DHA kinetics are disturbed in the disease.
    Journal of Psychiatric Research 09/2009; 44(3):177-82. DOI:10.1016/j.jpsychires.2009.08.001 · 4.09 Impact Factor