Omega-3 for Depression and Other Cardiac Risk Factors - 2

Depression increases the risk for cardiac morbidity and mortality 2-4 fold in patients with
coronary heart disease (CHD). Recent clinical trials have tested standard treatments for
comorbid depression in patients with CHD, and some have evaluated their effects on cardiac
morbidity and mortality. Most of these trials have shown that standard treatments have only
modest effects on depression and have produced relatively small differences between the
intervention and control condition. Consequently, they have been unable to determine whether
effective treatment of depression can improve cardiac outcomes. Low dietary intake and low
plasma phospholipid or erythrocyte levels of two omega-3 fatty acids(FAs), eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA), are associated with depression and other cardiac
risk markers. There is growing evidence from small psychiatric trials that the efficacy of
standard antidepressants can be improved by coadministration of an omega-3 FA formulation
containing at least 1 gram of EPA. The purpose of the proposed research is to determine
whether antidepressant augmentation with this omega-3 formulation is superior to
antidepressant therapy alone for major depression in patients with CHD. The proposed study is
a randomized, placebo-controlled, double-blind clinical trial. Consenting patients with
established coronary heart disease who meet the Diagnostic Statistical Manual (DSM)-5
criteria for a major depressive episode will undergo a baseline evaluation and then be
randomly assigned to receive either 50 mg/day of sertraline plus omega-3 FA or 50 mg/day of
sertraline plus placebo for 10 weeks. At baseline and after 10 weeks, participants will
complete assessments of depression, 24 hour ambulatory ECG monitoring to measure 24 hour
heart rate and heart rate variability, and blood draws to measure procoagulant and
proinflammatory markers and blood levels of EPA, DHA, other omega-3 FAs, and the omega-6 FAs.
If sertraline plus this omega-3 formulation significantly reduces depression compared to
sertraline plus placebo, and if it improves or at least does not worsen other cardiovascular
risk markers, this study will provide a strong basis for proposing a multicenter clinical
trial of sertraline augmented with omega-3 to determine whether treatment of depression can
improve survival in patients with CHD and depression.

Inclusion Criteria:

- Documented coronary heart disease

- Diagnosis of major depression based on structured interview

Exclusion Criteria:

- Moderate to severe cognitive impairment

- Meets DSM-5 criteria for depressive disorder due to a general medical condition or
medication

- Major Axis I psychiatric disorder other than unipolar depression or an anxiety
disorder, a high risk of suicide, or current substance abuse other than tobacco;

- Not expected to survive one year or physically unable to tolerate the study protocol

- Known sensitivity to sertraline or omega-3, or an allergy to fish oil or shellfish

- Taking an antidepressant or an omega-3 supplement at baseline

- Exempted by their cardiologist or primary care physician

- Refuses to provide informed consent

- Participating in a competing protocol or trial