Omega-3 Fatty Acids to Improve Depression and Reduce Cardiovascular Risk Factors

Omega-3 for Depression and Other Cardiac Risk Factors

This study will determine the effects of omega-3 fatty acid (FA) augmentation of sertraline on depression and cardiac endpoints after myocardial infarction (MI).

Study Overview

• Status: Completed
• Conditions: Depression; Myocardial Infarction; Heart Diseases; Cardiovascular Diseases; Angina, Unstable
• Intervention / Treatment: Drug: Sertraline/omega-3; Drug: Sertraline/Corn Oil

Detailed Description

BACKGROUND:

Depression is a risk factor for morbidity and mortality following an acute MI and unstable angina. Two recent studies (sertraline versus placebo and sertraline plus cognitive therapy versus usual care) reported only modest reductions in depression following an acute MI or unstable angina, and many treated patients remained depressed. Neither study reported better medical outcomes in the treated patients. Earlier studies found that even subclinical depression increases the risk of mortality in cardiac patients. Thus, more effective treatments are needed to eliminate depression and improve medical outcomes in patients following an acute MI or unstable angina. Omega-3 FAs have been shown to augment the efficacy of antidepressants for major depression and to improve several cardiac risk factors. However, these findings have been shown in separate lines of research. No previous study has investigated whether omega-3 FAs can simultaneously improve depression and reduce cardiovascular risk factors in post-MI patients.

DESIGN NARRATIVE:

One hundred fifty patients who meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for a current major depressive episode and who score 15 or higher on the Beck Depression Inventory II with a history of acute MI, unstable angina, or other cardiac event will be enrolled in a randomized, double-blind, placebo-controlled trial of omega-3 augmentation of sertraline. The participants will be randomly assigned to receive either sertraline plus omega-3 or sertraline plus placebo for 10 weeks. At baseline and again after ten weeks, the subjects will complete the following: 1) assessments of depression and psychosocial functioning; 2) 24-hour electrocardiogram monitoring for heart rate variability analysis; and 3) blood draws to measure procoagulant and proinflammatory markers, and plasma levels of sertraline and omega-3. If this study shows that omega-3 reduces depression and improves cardiovascular disease markers, there will be a basis for proposing a larger clinical trial to determine whether it can also improve survival after hospitalization for acute MI or unstable angina.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63108
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets the DSM-IV criteria for a current major depressive episode
• Score of 15 or higher on the Beck Depression Inventory II
• History of acute myocardial infarction, unstable angina, or documented coronary disease

Exclusion Criteria:

• Physician or patient refusal
• Lives far away from study site
• Current alcohol or drug abuse
• Psychosis, dementia, or bipolar disorder
• Already taking Omega-3
• Medically ill or disabled such that patient is unable to participate
• Comorbid illness likely to be fatal within 1 year of study entry
• Seizure disorder or takes anticonvulsants
• Pregnant or breast feeding
• Liver or kidney disease
• Severe hypertriglyceridemia (greater than 400 mg/dL)
• Bleeding or clotting disorder
• Type 2 diabetes with a hemoglobin A1c (HbA1c) level greater than 10
• Taking lithium or monoamine oxidase inhibitor (MAO-I)

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
Active Comparator: Sertraline/omega-3 supplement	Drug: Sertraline/omega-3; Sertraline (50 mgs) plus omega-3 (2 grams)
Placebo Comparator: Sertraline/corn oil	Drug: Sertraline/Corn Oil; Sertraline (50 mgs) plus corn oil (2 grams) (placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory-II	Beck Depression Inventory-II scores on a scale of 0 to 63, minimum score equals 0 maximum score equals 63. Higher value represents a worse outcome. Baseline scores are compared to scores after treatment.	Measured at Baseline and 10 weeks

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: Robert M. Carney, PhD, Washington University School of Medicine

Publications and helpful links

General Publications

• Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, Perry R. Omega-3 fatty acids for depression in adults. Cochrane Database Syst Rev. 2021 Nov 24;11(11):CD004692. doi: 10.1002/14651858.CD004692.pub5.
• Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS. Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial. JAMA. 2009 Oct 21;302(15):1651-7. doi: 10.1001/jama.2009.1487.
• Carney RM, Steinmeyer BC, Freedland KE, Rubin EH, Rich MW, Harris WS. Baseline blood levels of omega-3 and depression remission: a secondary analysis of data from a placebo-controlled trial of omega-3 supplements. J Clin Psychiatry. 2016 Feb;77(2):e138-43. doi: 10.4088/JCP.14m09660.
• Bot M, Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Mann DL. Inflammation and treatment response to sertraline in patients with coronary heart disease and comorbid major depression. J Psychosom Res. 2011 Jul;71(1):13-7. doi: 10.1016/j.jpsychores.2010.11.006. Epub 2011 Jan 15.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: June 30, 2005
• First Submitted That Met QC Criteria: June 30, 2005
• First Posted (Estimate): July 1, 2005

Study Record Updates

• Last Update Posted (Estimate): September 12, 2012
• Last Update Submitted That Met QC Criteria: September 11, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Vascular Diseases; Mood Disorders; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Myocardial Infarction; Infarction; Heart Diseases; Depression; Depressive Disorder; Cardiovascular Diseases; Angina, Unstable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: 186; R01HL076808 (U.S. NIH Grant/Contract)