Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study

Andrew F. Leuchter*, Ian A. Cook, Lauren B. Marangell, William S. Gilmer, Karl S. Burgoyne, Robert H. Howland, Madhukar H. Trivedi, Sidney Zisook, Rakesh Jain, James T. McCracken, Maurizio Fava, Dan Iosifescu, Scott Greenwald

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

Abstract

Patients with Major Depressive Disorder (MDD) may not respond to antidepressants for 8 weeks or longer. A biomarker that predicted treatment effectiveness after only 1 week could be clinically useful. We examined a frontal quantitative electroencephalographic (QEEG) biomarker, the Antidepressant Treatment Response (ATR) index, as a predictor of response to escitalopram, and compared ATR with other putative predictors. Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study. After 1 week of treatment with escitalopram, 10 mg, a second QEEG was performed, and the ATR was calculated. Subjects then were randomly assigned to continue with escitalopram, 10 mg, or change to alternative treatments. Seventy-three evaluable subjects received escitalopram for a total of 49 days. Response and remission rates were 52.1% and 38.4%, respectively. The ATR predicted both response and remission with 74% accuracy. Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors. Responders had larger decreases in Hamilton Depression Rating Scale (Ham-D17) scores at day 7 (P = 0.005), but remitters did not. Clinician prediction based upon global impression of improvement at day 7 did not predict outcome. Logistic regression showed that the ATR and early Ham-D17 changes were additive predictors of response, but the ATR was the only significant predictor of remission. Future studies should replicate these results prior to clinical use.

Original languageEnglish (US)
Pages (from-to)124-131
Number of pages8
JournalPsychiatry Research
Volume169
Issue number2
DOIs
StatePublished - Sep 30 2009

Funding

Aspect Medical Systems provided financial support of this project. Aspect participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript. Final approval of the form and content of the manuscript rests with the authors. Andrew Leuchter , M.D., has provided scientific consultation or served on advisory boards for Aspect Medical Systems, Eli Lilly and Company, Novartis Pharmaceuticals, MEDACorp, AstraZeneca, Takeda Pharmaceuticals, and Merck & Co. He has served on a speaker's bureau for Eli Lilly and Company and Wyeth-Ayerst Pharmaceuticals. He has received research/grant support from the National Institute of Mental Health, the National Center for Complementary and Alternative Medicine, Aspect Medical Systems, Eli Lilly and Company, Novartis Pharmaceuticals, Wyeth-Ayerst Pharmaceuticals, Merck & Co., Pfizer, Vivometrics, and MedAvante. He also is a minor stockholder in Aspect Medical Systems.

Keywords

  • Antidepressant Treatment Response (ATR) index
  • Escitalopram
  • Genetic polymorphisms
  • Major depression
  • Predictors of treatment response
  • Quantitative electroencephalography

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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