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

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

The purpose of this 10 week randomized, placebo-controlled, double-blind clinical trial is to determine whether antidepressant augmentation with two grams of EPA omega-3 per day is superior to antidepressant therapy alone for major depression in patients with coronary heart disease (CHD).

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Drug: Omega-3 supplement; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omega-3 supplement; Two grams of the EPA form of omega-3 plus 50 mg of sertraline daily for 10 weeks	Drug: Omega-3 supplement; Two grams of the EPA form of omega-3 daily and 50 mgs of sertraline daily for 10 weeks; Other Names: EPA Plus Minami Nutrition
Placebo Comparator: Placebo; Two grams of corn oil plus 50 mg of sertraline daily for 10 weeks.	Drug: Placebo; Two grams of corn oil plus 50 mg of sertraline daily for 10 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory-II (BDI-II)	The BDI-II is a 21-item self-report inventory of depression symptoms. The minimum and maximum values for the BDI-II are (0-63). For both instruments, the higher the scores, the greater the severity of depression.	Change from baseline to 10 weeks (post-treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale (HAM-D, 17)	The HAM-D, 17 is a 17-item, observer-rated measure of depression symptoms. The minimum and maximum values for the HAM-D, (0-52). For both instruments, the higher the scores, the greater the severity of depression.	Change from baseline to 10 weeks (post-treatment)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS. A Randomized Placebo-Controlled Trial of Omega-3 and Sertraline in Depressed Patients With or at Risk for Coronary Heart Disease. J Clin Psychiatry. 2019 Jun 4;80(4):19m12742. doi: 10.4088/JCP.19m12742.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2014
• Primary Completion (Actual): September 13, 2018
• Study Completion (Actual): September 13, 2018

Study Registration Dates

• First Submitted: December 19, 2013
• First Submitted That Met QC Criteria: December 19, 2013
• First Posted (Estimate): December 27, 2013

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 23, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Depression; Depressive disorder; Coronary disease; Fatty Acids, Omega-3; Antidepressive agents
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 201309002; R01HL117805 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO