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Original Research

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

Ian A. Cook, MD; Aimee M. Hunter, PhD; William S. Gilmer, MD; Dan V. Iosifescu, MD, MSc; Sidney Zisook, MD; Karl S. Burgoyne, MD; Robert H. Howland, MD; Madhukar H. Trivedi, MD; Rakesh Jain, MD, MPH; Scott Greenwald, PhD; and Andrew F. Leuchter, MD

Published: January 15, 2013

Article Abstract

Objective: Clinical trials in major depressive disorder (MDD) commonly assess remission at a single endpoint. Complementary, clinically relevant metrics include the likelihood and speed of achieving sustained remission. A neurophysiologic measure, the Antidepressant Treatment Response (ATR) index, previously predicted 8-week outcomes of pharmacotherapy. We retrospectively examined data from the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) trial to evaluate this biomarker’s properties in predicting sustained remission and time to achieve sustained remission.

Method: In the BRITE-MD trial, 67 adults with DSM-IV MDD received escitalopram continuously for 13 weeks. The 17-item Hamilton Depression Rating Scale (HDRS17) was used to define sustained remission as achieving remission (HDRS17 score ≤ 7) at a series of consecutive assessments, including week 13. The onset of sustained remission was defined as the earliest time from which all subsequent HDRS17 assessments were ≤ 7. The ATR was evaluated by using frontal quantitative electroencephalogram recordings at baseline and week 1. Subjects were stratified based on ATR status (ie, ATR+/ATR−). Kaplan-Meier survival analysis evaluated group differences in time to sustained remission. Higher ATR was hypothesized to predict sustained remission and time to sustained remission. Subjects participated between January 2006 and July 2007.

Results: Of 67 subjects, 36 achieved remission by week 13, and ATR predicted this single endpoint in receiver operating characteristic analyses (P = .016; sensitivity, 52.8%; positive predictive value, 76.0%). Remitters had a higher mean (SD) ATR value than those who did not remit (57.9 [10.0] vs 51.9 [8.7], P = .012). Sixteen of the 31 individuals with sustained remission had ATR+ status, while 28 of the 36 who were not sustained remitters had ATR- status (P = .012). The mean time to reach sustained remission was significantly shorter among ATR+ subjects than ATR- individuals (38 vs 53 days, P = .038).

Conclusions: The ATR index predicted remission at 13 weeks as well as the speed of achieving sustained remission with antidepressant monotherapy. This finding suggests that the ATR biomarker may predict stable longer-term outcomes.

Trial Registration: identifier: NCT00289523

J Clin Psychiatry 2013;74(1):51-56

Submitted: December 23, 2010; accepted September 10, 2012 (doi:10.4088/JCP.10m06813).

Corresponding author: Ian A. Cook, MD, UCLA Depression Research & Clinic Program, 760 Westwood Plaza, Los Angeles, CA 90095-1759 (

Volume: 74

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