This study will examine the effectiveness of omega-3 fatty acids, compounds found in plants
and fish, in treating bipolar disorder.
Some studies have indicated that omega-3 fatty acids may be effective in treating mood
For example, one investigator has shown a correlation between the prevalence of major
depression and the amount of fish consumed per capita worldwide. Others have found
decreased amounts of EPA (one of the active ingredients in omega-3 fatty acids) in the red
blood cells of patients with major depression. And a recent small study of patients with
bipolar illness indicated that omega-3 fatty acids prevented relapses, especially of
depression, in patients.
Patients with bipolar disorder who are not benefiting satisfactorily on their current
medications are eligible to participate in this study. Candidates will be screened with a
psychiatric evaluation, routine blood tests, a urine test and other tests needed to monitor
medications. Participants will be randomly assigned to one of two groups: one group will
receive 6 grams of omega-3 fatty acid every day for 16 weeks; the second will receive a
placebo (inactive capsule). In addition, patients in both groups will continue to take
their previous medications. Every 2 weeks, all patients will have their vital signs checked
and be evaluated for side effects and mood changes. At the end of the 16-week study period,
all patients will be given the opportunity to continue in the study for another 8 months and
receive active drug (omega-3 fatty acid). Patients who continue will be evaluated once a
month and will have blood drawn on the last visit for routine tests.
The aim of this study is to examine the efficacy of omega-3 fatty acids in the form of
eicosapentaenoic ethyl esters (EPA) - in the treatment of bipolar disorder. Omega-3 fatty
acids are long-chain, polyunsaturated fatty acids found in plant and marine sources. There
are preliminary data to suggest that omega-3 fatty acids may be efficacious in the treatment
of mood disorders. Patients in our bipolar outpatient clinic will be at one of the five
NIMH - Stanley Foundation Bipolar Network (the "Network") sites participating in this
project. Subjects will be randomly assigned in a double-blind manner to 6 grams per day of
omega-3 fatty acids or placebo (paraffin capsules) as an "add-on" to ongoing treatment with
mood stabilizing medication(s) which have proven unsatisfactorily effective within
therapeutic range(s) or at maximum tolerated dose(s). The double-blind trial will continue
for 4 months duration. Patients will then be offered the option of entering an eight month,
open-label trial of omega-3 fatty acid. The hypothesis of this study is that omega-3
polyunsaturated fatty acids in the form of eicosapentaenoic acid (EPA) acting on some of the
same signal transduction mechanisms as the mood stabilizers will be beneficial in
breakthrough depression, mania and cycling of bipolar disorder.
Patients must meet DSM-IV criteria for Bipolar Disorder, depressed, hypomanic/manic, or
Patients must be competent to comprehend the purpose of the study and provide informed
Patients must be at least 18 years old.
Patients enrolling in the bipolar depression component of the study must have a depression
of sufficient severity to rate greater than or equal to 16 on the Inventory of Depressive
Symptomatology-Clinician (IDS-C), or the clinician must decide there is a need to treat.
Patients enrolling in the bipolar hypomania/mania component of the study must have a
hypomania/mania of sufficient severity to rate greater than or equal to 12 on the Young
Mania Rating Scale or the clinician must decide that there is a need to treat.
Patients enrolling in the bipolar rapid cycling component of the study must have mood
fluctuations meeting one or both of the above acute episode criteria in the past 3 months
or show a pattern of ultra rapid cycling (4 or more episodes within a month) or ultradian
cycling (cycling within a day on 4 or more days/week) on the NIMH-LCM.
Patients must not have a serious medical illness.
Patients must not have non-insulin dependent diabetes mellitus (NIDDM) or
insulin-dependent diabetes mellitus (IDDM).
Patients must not have acute suicidal or homicidal ideation.