Omega 3 for Treatment of Depression in Patients With Heart Failure

The primary objective of this study is to determine whether (Hypothesis 1a) and how
(Hypothesis 1b) the two omega 3 supplements will reduce depressive symptoms in heart failure
(HF) patients with moderate-to-severe major depressive disorder (MDD).

Hypothesis 1a: Omega 3 supplements will improve depressive symptoms to a greater extent than
placebo; Hypothesis 1b: Pure eicosapentaenoic acid (EPA) will be superior to the EPA:
docosahexaenoic acid (DHA) 2:1 in depression improvement.

Inclusion Criteria:

- Adult male and female patients, age greater than or equal to 21 years

- Diagnosis of Major Depressive Disorder determined by the Diagnostic and Statistical
Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria with a
Hamilton Depression Rating Scale Score greater than or equal to 18*

- New York Heart Association Class greater than or equal to II

- For patients with with left ventricular ejection fraction greater than 40 %,
abnormal brain natriuretic peptide and/or previous hospitalization due to heart
failure is also required

- For inpatients, the Hamilton Depression Rating Scale scores need to be remain at
18 or above for two weeks following the discharge

Exclusion Criteria:

- Significant cognitive impairment, indicated as a Mini-Mental State Examination (MMSE)
total score of 23 or lower

- History of alcohol or other drug dependence within the past 90 days

- Severe physical disability (visual, sensory, or motor) that may interfere with
psychiatric assessment

- History or presence of psychoses, bipolar disorder, and/or severe personality
disorders

- Life-threatening comorbidity with the likelihood of 50% mortality in one year

- Active suicidal ideations

- Current use of antipsychotic medications or psychotropic medications except Selective
Serotonin Reuptake Inhibitors (SSRIs) and /or benzodiazepine

- Female patients who have a positive pregnancy test or are lactating. If female
patients are of childbearing potential, they must use an effective and accepted means
of contraception, such as oral contraceptives or a double-barrier method (condom and
diaphragm) to protect against pregnancy

- Documented history of hypersensitivity or intolerance to omega 3 products; or use of
omega 3 supplement for greater than or equal to 3 months at an equivalent or greater
dose of the proposed study

- Treatment with electroconvulsive therapy (ECT) or transcranial magnetic stimulation
(TMS) within 90 days*

- Uncorrected hypothyroidism or hyperthyroidism

- Treatment with any investigational agent within 1 month before randomization

- Acute coronary syndrome, i.e., Myocardial Infarction (MI) or unstable angina,
revascularization procedure within the preceding month, or planned cardiac surgery
within 3 months postrandomization

- The exclusion of patients who received ECT or TMS within 90 days is adopted from
other depression-intervention trials and meant to eliminate confounders. It is
believed that the effects of ECT on mood and cognition may last for a couple of
months, and duration of TMS effects is poorly known and may be similar to the ECT
intervention.