Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder

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

doi:10.1016/j.psychres.2009.04.004

Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder

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

^*Corresponding author for this work

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

111 Scopus citations

Abstract

We examined the Antidepressant Treatment Response (ATR) index as a predictor of differential response and remission to escitalopram, bupropion, or a combination of the two medications, in subjects with major depressive disorder (MDD). Three hundred seventy-five subjects had a baseline quantitative electroencephalographic (QEEG) study preceding 1 week of treatment with escitalopram, 10 mg, after which a second QEEG was performed and the ATR index was calculated. Subjects then were randomized to continue escitalopram, switch to bupropion, or receive a combination of the two. Clinical response was assessed using the 17-item Hamilton Depression Rating Scale at 49 days of treatment. Accuracy of ATR in predicting response and remission was calculated. There were no significant differences between response and remission rates in the three treatment groups. A single ATR threshold was useful for predicting differential response to either escitalopram or bupropion monotherapy. Subjects with ATR values above the threshold were more than 2.4 times as likely to respond to escitalopram as those with low ATR values (68% vs. 28%). Subjects with ATR values below the threshold who were switched to bupropion treatment were 1.9 times as likely to respond to bupropion alone as those who remained on escitalopram treatment (53% vs. 28%). The ATR index did not provide a useful prediction of response to combination treatment. The ATR index may prove useful in predicting responsiveness to different antidepressant medications.

Original language	English (US)
Pages (from-to)	132-138
Number of pages	7
Journal	Psychiatry Research
Volume	169
Issue number	2
DOIs	https://doi.org/10.1016/j.psychres.2009.04.004
State	Published - Sep 30 2009

Funding

Financial support of this project was provided by Aspect Medical Systems. 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 of Aspect Medical Systems. Ian A. Cook, M.D. , has served as an advisor and consultant for Ascend Media, Bristol-Meyers Squibb, Cyberonics Inc., and Janssen. He has served on the Speaker's Bureau for Bristol‐Meyers Squibb, Medical Education Speakers Network, Pfizer Pharmaceuticals Inc., and Wyeth Pharmaceuticals. Dr. Cook received research support from the Aspect Medical Systems, Cyberonics Inc., Eli Lilly & Company, Novartis Pharmaceuticals, Pfizer, Inc., and Sepracor. William S. Gilmer, M.D. , has served on the Speaker's Bureau for GlaxoSmithKline and Pfizer. He has also received honoraria from GlaxoSmithKline and Pfizer, Inc. Additionally, Dr. Gilmer received research support from Abbott, Aspect Medical Systems, Forest Pharmaceuticals, Janssen, the National Institute of Mental Health, Neuronetics, Novartis Pharmaceuticals, and Pfizer. Lauren Marangell, M.D. , currently is an employee of the Eli Lilly and Company, Indianapolis, IN. The work described in this manuscript was performed while she was on the faculty of the Baylor College of Medicine and does not necessarily reflect the views of Eli Lilly and Company. She previously served as a consultant for, or received lecture honoraria from the Aspect Medical Systems, Cyberonics, Inc., Medtronics, GlaxoSmithKline, Pfizer, Inc., Novartis Pharmaceuticals, and Forest Pharmaceuticals. Dr. Marangell had received research support from Bristol‐Myers Squibb Company, Cyberonics, Inc., Neuronetics, National Institute of Mental Health, Stanley Foundation, NARSAD, American Foundation for Suicide Prevention, Aspect Medical Systems, and Sanofi‐Aventis. Karl S. Burgoyne, M.D. , has received research support from the Aspect Medical Systems. Robert H. Howland, M.D. , has received research support from the Aspect Medical Systems, Bristol‐Myers Squibb, Cederroth, Cyberonics Inc., Forest Pharmaceuticals, and Novartis Pharmaceuticals. Sidney Zisook, M.D. , has served as an advisor and consultant for Glaxo-Smith Kline. He has served on the Speaker's Bureau for Glaxo-Smith Kline and Forest Laboratories. Additionally, Dr. Zisook has received research support from the Aspect Medical Systems, PemLab, and Jed Foundation.

Keywords

Antidepressant treatment response (ATR) index
Bupropion
Differential medication response
Escitalopram
Major depression
Quantitative electroencephalography

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.psychres.2009.04.004

Cite this

Leuchter, A. F., Cook, I. A., Gilmer, W. S., Marangell, L. B., Burgoyne, K. S., Howland, R. H., Trivedi, M. H., Zisook, S., Jain, R., Fava, M., Iosifescu, D., & Greenwald, S. (2009). Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder. Psychiatry Research, 169(2), 132-138. https://doi.org/10.1016/j.psychres.2009.04.004

@article{c64e4fdc0646455d863d000e75a382c6,

title = "Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder",

abstract = "We examined the Antidepressant Treatment Response (ATR) index as a predictor of differential response and remission to escitalopram, bupropion, or a combination of the two medications, in subjects with major depressive disorder (MDD). Three hundred seventy-five subjects had a baseline quantitative electroencephalographic (QEEG) study preceding 1 week of treatment with escitalopram, 10 mg, after which a second QEEG was performed and the ATR index was calculated. Subjects then were randomized to continue escitalopram, switch to bupropion, or receive a combination of the two. Clinical response was assessed using the 17-item Hamilton Depression Rating Scale at 49 days of treatment. Accuracy of ATR in predicting response and remission was calculated. There were no significant differences between response and remission rates in the three treatment groups. A single ATR threshold was useful for predicting differential response to either escitalopram or bupropion monotherapy. Subjects with ATR values above the threshold were more than 2.4 times as likely to respond to escitalopram as those with low ATR values (68% vs. 28%). Subjects with ATR values below the threshold who were switched to bupropion treatment were 1.9 times as likely to respond to bupropion alone as those who remained on escitalopram treatment (53% vs. 28%). The ATR index did not provide a useful prediction of response to combination treatment. The ATR index may prove useful in predicting responsiveness to different antidepressant medications.",

keywords = "Antidepressant treatment response (ATR) index, Bupropion, Differential medication response, Escitalopram, Major depression, Quantitative electroencephalography",

author = "Leuchter, {Andrew F.} and Cook, {Ian A.} and Gilmer, {William S.} and Marangell, {Lauren B.} and Burgoyne, {Karl S.} and Howland, {Robert H.} and Trivedi, {Madhukar H.} and Sidney Zisook and Rakesh Jain and Maurizio Fava and Dan Iosifescu and Scott Greenwald",

note = "Funding Information: Financial support of this project was provided by Aspect Medical Systems. 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 of Aspect Medical Systems. Funding Information: Ian A. Cook, M.D. , has served as an advisor and consultant for Ascend Media, Bristol-Meyers Squibb, Cyberonics Inc., and Janssen. He has served on the Speaker's Bureau for Bristol‐Meyers Squibb, Medical Education Speakers Network, Pfizer Pharmaceuticals Inc., and Wyeth Pharmaceuticals. Dr. Cook received research support from the Aspect Medical Systems, Cyberonics Inc., Eli Lilly & Company, Novartis Pharmaceuticals, Pfizer, Inc., and Sepracor. Funding Information: William S. Gilmer, M.D. , has served on the Speaker's Bureau for GlaxoSmithKline and Pfizer. He has also received honoraria from GlaxoSmithKline and Pfizer, Inc. Additionally, Dr. Gilmer received research support from Abbott, Aspect Medical Systems, Forest Pharmaceuticals, Janssen, the National Institute of Mental Health, Neuronetics, Novartis Pharmaceuticals, and Pfizer. Funding Information: Lauren Marangell, M.D. , currently is an employee of the Eli Lilly and Company, Indianapolis, IN. The work described in this manuscript was performed while she was on the faculty of the Baylor College of Medicine and does not necessarily reflect the views of Eli Lilly and Company. She previously served as a consultant for, or received lecture honoraria from the Aspect Medical Systems, Cyberonics, Inc., Medtronics, GlaxoSmithKline, Pfizer, Inc., Novartis Pharmaceuticals, and Forest Pharmaceuticals. Dr. Marangell had received research support from Bristol‐Myers Squibb Company, Cyberonics, Inc., Neuronetics, National Institute of Mental Health, Stanley Foundation, NARSAD, American Foundation for Suicide Prevention, Aspect Medical Systems, and Sanofi‐Aventis. Funding Information: Karl S. Burgoyne, M.D. , has received research support from the Aspect Medical Systems. Funding Information: Robert H. Howland, M.D. , has received research support from the Aspect Medical Systems, Bristol‐Myers Squibb, Cederroth, Cyberonics Inc., Forest Pharmaceuticals, and Novartis Pharmaceuticals. Funding Information: Sidney Zisook, M.D. , has served as an advisor and consultant for Glaxo-Smith Kline. He has served on the Speaker's Bureau for Glaxo-Smith Kline and Forest Laboratories. Additionally, Dr. Zisook has received research support from the Aspect Medical Systems, PemLab, and Jed Foundation. Copyright: Copyright 2009 Elsevier B.V., All rights reserved.",

year = "2009",

month = sep,

day = "30",

doi = "10.1016/j.psychres.2009.04.004",

language = "English (US)",

volume = "169",

pages = "132--138",

journal = "Psychiatry Research",

issn = "0165-1781",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

Leuchter, AF, Cook, IA, Gilmer, WS, Marangell, LB, Burgoyne, KS, Howland, RH, Trivedi, MH, Zisook, S, Jain, R, Fava, M, Iosifescu, D & Greenwald, S 2009, 'Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder', Psychiatry Research, vol. 169, no. 2, pp. 132-138. https://doi.org/10.1016/j.psychres.2009.04.004

Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder. / Leuchter, Andrew F.; Cook, Ian A.; Gilmer, William S. et al.
In: Psychiatry Research, Vol. 169, No. 2, 30.09.2009, p. 132-138.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder

AU - Leuchter, Andrew F.

AU - Cook, Ian A.

AU - Gilmer, William S.

AU - Marangell, Lauren B.

AU - Burgoyne, Karl S.

AU - Howland, Robert H.

AU - Trivedi, Madhukar H.

AU - Zisook, Sidney

AU - Jain, Rakesh

AU - Fava, Maurizio

AU - Iosifescu, Dan

AU - Greenwald, Scott

N1 - Funding Information: Financial support of this project was provided by Aspect Medical Systems. 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 of Aspect Medical Systems. Funding Information: Ian A. Cook, M.D. , has served as an advisor and consultant for Ascend Media, Bristol-Meyers Squibb, Cyberonics Inc., and Janssen. He has served on the Speaker's Bureau for Bristol‐Meyers Squibb, Medical Education Speakers Network, Pfizer Pharmaceuticals Inc., and Wyeth Pharmaceuticals. Dr. Cook received research support from the Aspect Medical Systems, Cyberonics Inc., Eli Lilly & Company, Novartis Pharmaceuticals, Pfizer, Inc., and Sepracor. Funding Information: William S. Gilmer, M.D. , has served on the Speaker's Bureau for GlaxoSmithKline and Pfizer. He has also received honoraria from GlaxoSmithKline and Pfizer, Inc. Additionally, Dr. Gilmer received research support from Abbott, Aspect Medical Systems, Forest Pharmaceuticals, Janssen, the National Institute of Mental Health, Neuronetics, Novartis Pharmaceuticals, and Pfizer. Funding Information: Lauren Marangell, M.D. , currently is an employee of the Eli Lilly and Company, Indianapolis, IN. The work described in this manuscript was performed while she was on the faculty of the Baylor College of Medicine and does not necessarily reflect the views of Eli Lilly and Company. She previously served as a consultant for, or received lecture honoraria from the Aspect Medical Systems, Cyberonics, Inc., Medtronics, GlaxoSmithKline, Pfizer, Inc., Novartis Pharmaceuticals, and Forest Pharmaceuticals. Dr. Marangell had received research support from Bristol‐Myers Squibb Company, Cyberonics, Inc., Neuronetics, National Institute of Mental Health, Stanley Foundation, NARSAD, American Foundation for Suicide Prevention, Aspect Medical Systems, and Sanofi‐Aventis. Funding Information: Karl S. Burgoyne, M.D. , has received research support from the Aspect Medical Systems. Funding Information: Robert H. Howland, M.D. , has received research support from the Aspect Medical Systems, Bristol‐Myers Squibb, Cederroth, Cyberonics Inc., Forest Pharmaceuticals, and Novartis Pharmaceuticals. Funding Information: Sidney Zisook, M.D. , has served as an advisor and consultant for Glaxo-Smith Kline. He has served on the Speaker's Bureau for Glaxo-Smith Kline and Forest Laboratories. Additionally, Dr. Zisook has received research support from the Aspect Medical Systems, PemLab, and Jed Foundation. Copyright: Copyright 2009 Elsevier B.V., All rights reserved.

PY - 2009/9/30

Y1 - 2009/9/30

N2 - We examined the Antidepressant Treatment Response (ATR) index as a predictor of differential response and remission to escitalopram, bupropion, or a combination of the two medications, in subjects with major depressive disorder (MDD). Three hundred seventy-five subjects had a baseline quantitative electroencephalographic (QEEG) study preceding 1 week of treatment with escitalopram, 10 mg, after which a second QEEG was performed and the ATR index was calculated. Subjects then were randomized to continue escitalopram, switch to bupropion, or receive a combination of the two. Clinical response was assessed using the 17-item Hamilton Depression Rating Scale at 49 days of treatment. Accuracy of ATR in predicting response and remission was calculated. There were no significant differences between response and remission rates in the three treatment groups. A single ATR threshold was useful for predicting differential response to either escitalopram or bupropion monotherapy. Subjects with ATR values above the threshold were more than 2.4 times as likely to respond to escitalopram as those with low ATR values (68% vs. 28%). Subjects with ATR values below the threshold who were switched to bupropion treatment were 1.9 times as likely to respond to bupropion alone as those who remained on escitalopram treatment (53% vs. 28%). The ATR index did not provide a useful prediction of response to combination treatment. The ATR index may prove useful in predicting responsiveness to different antidepressant medications.

AB - We examined the Antidepressant Treatment Response (ATR) index as a predictor of differential response and remission to escitalopram, bupropion, or a combination of the two medications, in subjects with major depressive disorder (MDD). Three hundred seventy-five subjects had a baseline quantitative electroencephalographic (QEEG) study preceding 1 week of treatment with escitalopram, 10 mg, after which a second QEEG was performed and the ATR index was calculated. Subjects then were randomized to continue escitalopram, switch to bupropion, or receive a combination of the two. Clinical response was assessed using the 17-item Hamilton Depression Rating Scale at 49 days of treatment. Accuracy of ATR in predicting response and remission was calculated. There were no significant differences between response and remission rates in the three treatment groups. A single ATR threshold was useful for predicting differential response to either escitalopram or bupropion monotherapy. Subjects with ATR values above the threshold were more than 2.4 times as likely to respond to escitalopram as those with low ATR values (68% vs. 28%). Subjects with ATR values below the threshold who were switched to bupropion treatment were 1.9 times as likely to respond to bupropion alone as those who remained on escitalopram treatment (53% vs. 28%). The ATR index did not provide a useful prediction of response to combination treatment. The ATR index may prove useful in predicting responsiveness to different antidepressant medications.

KW - Antidepressant treatment response (ATR) index

KW - Bupropion

KW - Differential medication response

KW - Escitalopram

KW - Major depression

KW - Quantitative electroencephalography

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Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder

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