Clinical trial NCT00289523: EEG Biomarkers for Predicting Response to Antidepressant Therapy
Official title: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder, Depressive Disorder, Unipolar Depression, Antidepressants, Electroencephalography
Lead sponsor: Medtronic - MITG
Sponsor class: INDUSTRY
First posted: 2006-02-10
Enrollment: 375
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: 1. To confirm prospectively the accuracy of an EEG biomarker as a leading indicator of SSRI antidepressant treatment response;
timeFrame: 8 weeks
Secondary outcomes:
measure: 1. To confirm prospectively the accuracy of an EEG biomarker as a leading indicator of remission;
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles-Westwood
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Torrance
country: United States
facility: University of California, Los Angeles-Harbor
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas, Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor University College of Medicine
state: Texas
city: Lake Jackson
country: United States
facility: R/D Clinical Research, Inc.
state: Texas
Study officials:
affiliation: University of California, Los Angeles-Westwood
name: Andrew F Leuchter, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.