Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study
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 Antidepre...
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| Veröffentlicht in: | Psychiatry research 2009-09, Vol.169 (2), p.124-131 |
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| creator | Leuchter, Andrew F Cook, Ian A Marangell, Lauren B Gilmer, William S Burgoyne, Karl S Howland, Robert H Trivedi, Madhukar H Zisook, Sidney Jain, Rakesh McCracken, James T Fava, Maurizio Iosifescu, Dan Greenwald, Scott |
| description | 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. |
| doi_str_mv | 10.1016/j.psychres.2009.06.004 |
| format | Article |
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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.</description><identifier>ISSN: 0165-1781</identifier><identifier>EISSN: 1872-7123</identifier><identifier>DOI: 10.1016/j.psychres.2009.06.004</identifier><identifier>PMID: 19712979</identifier><identifier>CODEN: PSRSDR</identifier><language>eng</language><publisher>Kidlington: Elsevier Ireland Ltd</publisher><subject>Adolescent ; Adult ; Adult and adolescent clinical studies ; Aged ; Antidepressant Treatment Response (ATR) index ; Biological and medical sciences ; Biomarkers ; Citalopram - analogs & derivatives ; Citalopram - therapeutic use ; Depression ; Depressive Disorder, Major - drug therapy ; Depressive Disorder, Major - genetics ; Depressive Disorder, Major - pathology ; Depressive Disorder, Major - physiopathology ; Electroencephalography - methods ; Escitalopram ; Female ; Frontal Lobe - physiopathology ; Genetic polymorphisms ; Humans ; Major depression ; Male ; Medical sciences ; Middle Aged ; Mood disorders ; Neuropharmacology ; Pharmacology. Drug treatments ; Predictive Value of Tests ; Predictors of treatment response ; Psychiatric Status Rating Scales ; Psychiatry ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Quantitative electroencephalography ; Receptors, Serotonin - genetics ; ROC Curve ; Serotonin Uptake Inhibitors - blood ; Serotonin Uptake Inhibitors - therapeutic use ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; Young Adult</subject><ispartof>Psychiatry research, 2009-09, Vol.169 (2), p.124-131</ispartof><rights>Elsevier Ltd</rights><rights>2009 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-eba66de642bc48cb260491e8d350e497fe0f3193eb54002a5af5d08f2938e3033</citedby><cites>FETCH-LOGICAL-c517t-eba66de642bc48cb260491e8d350e497fe0f3193eb54002a5af5d08f2938e3033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0165178109002121$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21975656$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19712979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leuchter, Andrew F</creatorcontrib><creatorcontrib>Cook, Ian A</creatorcontrib><creatorcontrib>Marangell, Lauren B</creatorcontrib><creatorcontrib>Gilmer, William S</creatorcontrib><creatorcontrib>Burgoyne, Karl S</creatorcontrib><creatorcontrib>Howland, Robert H</creatorcontrib><creatorcontrib>Trivedi, Madhukar H</creatorcontrib><creatorcontrib>Zisook, Sidney</creatorcontrib><creatorcontrib>Jain, Rakesh</creatorcontrib><creatorcontrib>McCracken, James T</creatorcontrib><creatorcontrib>Fava, Maurizio</creatorcontrib><creatorcontrib>Iosifescu, Dan</creatorcontrib><creatorcontrib>Greenwald, Scott</creatorcontrib><title>Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study</title><title>Psychiatry research</title><addtitle>Psychiatry Res</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Aged</subject><subject>Antidepressant Treatment Response (ATR) index</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Citalopram - analogs & derivatives</subject><subject>Citalopram - therapeutic use</subject><subject>Depression</subject><subject>Depressive Disorder, Major - drug therapy</subject><subject>Depressive Disorder, Major - genetics</subject><subject>Depressive Disorder, Major - pathology</subject><subject>Depressive Disorder, Major - physiopathology</subject><subject>Electroencephalography - methods</subject><subject>Escitalopram</subject><subject>Female</subject><subject>Frontal Lobe - physiopathology</subject><subject>Genetic polymorphisms</subject><subject>Humans</subject><subject>Major depression</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mood disorders</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Predictive Value of Tests</subject><subject>Predictors of treatment response</subject><subject>Psychiatric Status Rating Scales</subject><subject>Psychiatry</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Quantitative electroencephalography</subject><subject>Receptors, Serotonin - genetics</subject><subject>ROC Curve</subject><subject>Serotonin Uptake Inhibitors - blood</subject><subject>Serotonin Uptake Inhibitors - therapeutic use</subject><subject>Severity of Illness Index</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0165-1781</issn><issn>1872-7123</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAURiMEokPhFSpvYJfBzo8Ts0DATIGRWiHNlLXlONfU0yQOvk6leSDeE6czBYkNK9vR-ezoOzdJLhhdMsr42_1yxIO-9YDLjFKxpHxJafEkWbC6ytKKZfnTZBHBMmVVzc6SF4h7SmnGhHienDERCVGJRfJr5fpReRXsPRAwBvS8GwCROEMa63rl78AjUUNLdGcHq1VH7NDGNbj43ThPRg_xHOzwg7gpaNfDQ3q3225I8KBCD0OIIXKt9hFfQwwgzi-uLTrfgn9HtoBTFx5y4RbIp-3m5jK9XhMMU3t4mTwzqkN4dVrPk--fL29WX9Orb182q49XqS5ZFVJoFOct8CJrdFHrJuO0EAzqNi8pFKIyQE3ORA5NWcQuVKlM2dLaZCKvIad5fp68Od47evdzAgyyt6ih69QAbkLJK55XZVZEkB9B7R2iByNHb2NVB8monAXJvXwUJGdBknIZBcXgxemFqemh_Rs7GYnA6xOgMFZtvBq0xT9cFFiVvOSR-3DkIPZxb8FL1BYGHU34KFG2zv7_X97_c8Wj4Ds4AO7d5IfYtmQSM0nlbh6neZqomAcpY_lvVGXKEg</recordid><startdate>20090930</startdate><enddate>20090930</enddate><creator>Leuchter, Andrew F</creator><creator>Cook, Ian A</creator><creator>Marangell, Lauren B</creator><creator>Gilmer, William S</creator><creator>Burgoyne, Karl S</creator><creator>Howland, Robert H</creator><creator>Trivedi, Madhukar H</creator><creator>Zisook, Sidney</creator><creator>Jain, Rakesh</creator><creator>McCracken, James T</creator><creator>Fava, Maurizio</creator><creator>Iosifescu, Dan</creator><creator>Greenwald, Scott</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090930</creationdate><title>Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study</title><author>Leuchter, Andrew F ; Cook, Ian A ; Marangell, Lauren B ; Gilmer, William S ; Burgoyne, Karl S ; Howland, Robert H ; Trivedi, Madhukar H ; Zisook, Sidney ; Jain, Rakesh ; McCracken, James T ; Fava, Maurizio ; Iosifescu, Dan ; Greenwald, Scott</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-eba66de642bc48cb260491e8d350e497fe0f3193eb54002a5af5d08f2938e3033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Aged</topic><topic>Antidepressant Treatment Response (ATR) index</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Citalopram - analogs & derivatives</topic><topic>Citalopram - therapeutic use</topic><topic>Depression</topic><topic>Depressive Disorder, Major - drug therapy</topic><topic>Depressive Disorder, Major - genetics</topic><topic>Depressive Disorder, Major - pathology</topic><topic>Depressive Disorder, Major - physiopathology</topic><topic>Electroencephalography - methods</topic><topic>Escitalopram</topic><topic>Female</topic><topic>Frontal Lobe - physiopathology</topic><topic>Genetic polymorphisms</topic><topic>Humans</topic><topic>Major depression</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mood disorders</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Predictive Value of Tests</topic><topic>Predictors of treatment response</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychiatry</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Quantitative electroencephalography</topic><topic>Receptors, Serotonin - genetics</topic><topic>ROC Curve</topic><topic>Serotonin Uptake Inhibitors - blood</topic><topic>Serotonin Uptake Inhibitors - therapeutic use</topic><topic>Severity of Illness Index</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leuchter, Andrew F</creatorcontrib><creatorcontrib>Cook, Ian A</creatorcontrib><creatorcontrib>Marangell, Lauren B</creatorcontrib><creatorcontrib>Gilmer, William S</creatorcontrib><creatorcontrib>Burgoyne, Karl S</creatorcontrib><creatorcontrib>Howland, Robert H</creatorcontrib><creatorcontrib>Trivedi, Madhukar H</creatorcontrib><creatorcontrib>Zisook, Sidney</creatorcontrib><creatorcontrib>Jain, Rakesh</creatorcontrib><creatorcontrib>McCracken, James T</creatorcontrib><creatorcontrib>Fava, Maurizio</creatorcontrib><creatorcontrib>Iosifescu, Dan</creatorcontrib><creatorcontrib>Greenwald, Scott</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Psychiatry research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leuchter, Andrew F</au><au>Cook, Ian A</au><au>Marangell, Lauren B</au><au>Gilmer, William S</au><au>Burgoyne, Karl S</au><au>Howland, Robert H</au><au>Trivedi, Madhukar H</au><au>Zisook, Sidney</au><au>Jain, Rakesh</au><au>McCracken, James T</au><au>Fava, Maurizio</au><au>Iosifescu, Dan</au><au>Greenwald, Scott</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study</atitle><jtitle>Psychiatry research</jtitle><addtitle>Psychiatry Res</addtitle><date>2009-09-30</date><risdate>2009</risdate><volume>169</volume><issue>2</issue><spage>124</spage><epage>131</epage><pages>124-131</pages><issn>0165-1781</issn><eissn>1872-7123</eissn><coden>PSRSDR</coden><abstract>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.</abstract><cop>Kidlington</cop><pub>Elsevier Ireland Ltd</pub><pmid>19712979</pmid><doi>10.1016/j.psychres.2009.06.004</doi><tpages>8</tpages></addata></record> |
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| ispartof | Psychiatry research, 2009-09, Vol.169 (2), p.124-131 |
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| subjects | Adolescent Adult Adult and adolescent clinical studies Aged Antidepressant Treatment Response (ATR) index Biological and medical sciences Biomarkers Citalopram - analogs & derivatives Citalopram - therapeutic use Depression Depressive Disorder, Major - drug therapy Depressive Disorder, Major - genetics Depressive Disorder, Major - pathology Depressive Disorder, Major - physiopathology Electroencephalography - methods Escitalopram Female Frontal Lobe - physiopathology Genetic polymorphisms Humans Major depression Male Medical sciences Middle Aged Mood disorders Neuropharmacology Pharmacology. Drug treatments Predictive Value of Tests Predictors of treatment response Psychiatric Status Rating Scales Psychiatry Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Quantitative electroencephalography Receptors, Serotonin - genetics ROC Curve Serotonin Uptake Inhibitors - blood Serotonin Uptake Inhibitors - therapeutic use Severity of Illness Index Time Factors Treatment Outcome Young Adult |
| title | Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study |
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