title: 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.
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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00289523.
authors: UCLA Semel Institute for Neuroscience and Human Behavior, Depression Research & Clinic Program and Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. icook@ucla.edu
authors: Ian A
authors: IA
authors: Cook
authors: Aimee M
authors: AM
authors: Hunter
authors: William S
authors: WS
authors: Gilmer
authors: Dan V
authors: DV
authors: Iosifescu
authors: Sidney
authors: S
authors: Zisook
authors: Karl S
authors: KS
authors: Burgoyne
authors: Robert H
authors: RH
authors: Howland
authors: Madhukar H
authors: MH
authors: Trivedi
authors: Rakesh
authors: R
authors: Jain
authors: Scott
authors: S
authors: Greenwald
authors: Andrew F
authors: AF
authors: Leuchter
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D016642:Bupropion / Q000009:adverse effects / Q000627:therapeutic use*; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects* / Q000706:statistics & numerical data*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011594:Psychometrics; D055502:Secondary Prevention; D012815:Signal Processing, Computer-Assisted; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D016642:Bupropion; D015283:Citalopram