TY - JOUR
T1 - Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder
T2 - Results of the BRITE-MD study
AU - Leuchter, Andrew F.
AU - Cook, Ian A.
AU - Marangell, Lauren B.
AU - Gilmer, William S.
AU - Burgoyne, Karl S.
AU - Howland, Robert H.
AU - Trivedi, Madhukar H.
AU - Zisook, Sidney
AU - Jain, Rakesh
AU - McCracken, James T.
AU - Fava, Maurizio
AU - Iosifescu, Dan
AU - Greenwald, Scott
N1 - Funding Information:
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.
Funding Information:
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.
PY - 2009/9/30
Y1 - 2009/9/30
N2 - 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.
AB - 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.
KW - Antidepressant Treatment Response (ATR) index
KW - Escitalopram
KW - Genetic polymorphisms
KW - Major depression
KW - Predictors of treatment response
KW - Quantitative electroencephalography
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U2 - 10.1016/j.psychres.2009.06.004
DO - 10.1016/j.psychres.2009.06.004
M3 - Article
C2 - 19712979
AN - SCOPUS:69649101602
SN - 0165-1781
VL - 169
SP - 124
EP - 131
JO - Psychiatry research
JF - Psychiatry research
IS - 2
ER -