EEG Biomarkers for Predicting Response to Antidepressant Therapy

Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD), a Prospective, Randomized, Multi-center Study to Determine the Efficacy of Selected EEG and Genotype Biomarkers for Predicting Response to Antidepressant Therapy With Escitalopram, Bupropion XL, or a Combination Treatment Regimen.

The purpose of this study is to evaluate the potential early EEG predictors of an individual's response to treatment with antidepressant medications.

Objectives:

• Prospectively confirm accuracy of current EEG biomarker algorithm
• Determine preferred clinical intervention for subjects with negative indicator
• Identify predictors of worsening suicide ideation

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder

Detailed Description

According to recent clinical studies sponsored by the NIH, fewer than half of subjects diagnosed with a major depressive episode respond to the first trial of an antidepressant medication. While the majority of subjects eventually respond to treatment with an antidepressant, failure with the first line medication puts subjects at increased risk for never receiving adequate treatment of their depression.

Several lines of reasoning support the rationale for further investigating EEG as a means of predicting response and resistance to antidepressants. Prior studies suggest that changes in neuronal activity in the anterior cingulate and prefrontal regions are related to depression and that changes in brain response to treatment may also produce alterations that can be detected by recoding frontal EEG activity.

In this protocol, we proposed to identify possible neurophysiologic indicators of treatment outcome in depression, particularly indicators of brain response that appear early (within 7 days) during treatment with antidepressants. We will test whether quantitative EEG (QEEG) biomarkers can be reliably associated with response or non-response to treatment with antidepressant medications, using both monotherapy and combination drug treatments.

Comparison(s):

Selecting the best treatment for subjects with resistance to an initial antidepressant poses a considerable challenge for clinicians. The most widely prescribed antidepressants usually require 4-6 weeks of therapeutic dosing before a marked clinical improvement in symptoms is observed. Therefore, determining the optimal regimen can take several weeks or months for subjects who are resistant to the first line antidepressant. A tool for predicting eventual clinical response to antidepressants could help inform and accelerate the process of identifying the most efficacious treatment option for a given subject.

• Study Type: Observational
• Enrollment (Actual): 375

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles-Westwood
    • San Diego, California, United States, 92161
      • University of California, San Diego
    • Torrance, California, United States, 90509
      • University of California, Los Angeles-Harbor
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas, Southwestern
    • Houston, Texas, United States, 77030
      • Baylor University College of Medicine
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

A total of 375 subjects with major depressive disorder (MDD) between the ages of 18 - 75 with no other primary neuropsychiatric illnesses were recruited from the population presenting for ongoing treatment in a primary care clinic, or for depression in a psychiatric clinic at each site.

Description

Inclusion Criteria:

• Subject has diagnosis of Major Depressive Disorder

Exclusion Criteria:

• Subject is suffering from cognitive, bipolar, or psychotic disorder
• Subject has had a course of ECT within the past six months
• Subject has any known contraindication for use of any of the study drugs
• Subject has a known drug dependency or substance abuse within the past six mon ths
• Subject is currently pregnant or not using a medically acceptable means of birth control

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Escitalopram
Bupropion XL
Combination Therapy; Escitalopram and Bupropion XL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. To confirm prospectively the accuracy of an EEG biomarker as a leading indicator of SSRI antidepressant treatment response;	2. To identify the optimal positive and negative indicators of response to initial treatment with an SSRI; 3. To determine the preferred clinical intervention to perform following an initial negative treatment response indicator;	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. To confirm prospectively the accuracy of an EEG biomarker as a leading indicator of remission;	2. To explore the relationship between EEG and genetic biomarkers as predictors of treatment response and remission; 3. To determine if certain baseline EEG values or changes early in the course of treatment may predict the emergence of worsening suicidal ideation.	8 weeks

Collaborators and Investigators

• Sponsor: Medtronic - MITG
• Investigators: Principal Investigator: Andrew F Leuchter, M.D., University of California, Los Angeles-Westwood

Publications and helpful links

General Publications

• Leuchter AF, Cook IA, Marangell LB, Gilmer WS, Burgoyne KS, Howland RH, Trivedi MH, Zisook S, Jain R, McCracken JT, Fava M, Iosifescu D, Greenwald S. Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: results of the BRITE-MD study. Psychiatry Res. 2009 Sep 30;169(2):124-31. doi: 10.1016/j.psychres.2009.06.004. Epub 2009 Aug 27.
• Leuchter AF, Cook IA, Gilmer WS, Marangell LB, Burgoyne KS, Howland RH, Trivedi MH, Zisook S, Jain R, Fava M, Iosifescu D, Greenwald S. Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder. Psychiatry Res. 2009 Sep 30;169(2):132-8. doi: 10.1016/j.psychres.2009.04.004. Epub 2009 Aug 26.
• Cook IA, Hunter AM, Gilmer WS, Iosifescu DV, Zisook S, Burgoyne KS, Howland RH, Trivedi MH, Jain R, Greenwald S, Leuchter AF. Quantitative electroencephalogram biomarkers for predicting likelihood and speed of achieving sustained remission in major depression: a report from the biomarkers for rapid identification of treatment effectiveness in major depression (BRITE-MD) trial. J Clin Psychiatry. 2013 Jan;74(1):51-6. doi: 10.4088/JCP.10m06813.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: February 8, 2006
• First Submitted That Met QC Criteria: February 8, 2006
• First Posted (Estimate): February 10, 2006

Study Record Updates

• Last Update Posted (Estimate): March 7, 2012
• Last Update Submitted That Met QC Criteria: March 6, 2012
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: Major Depressive Disorder, Depressive Disorder, Unipolar Depression, Antidepressants, Electroencephalography
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 227