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.