title: 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 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 49days. 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-D(17)) 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-D(17) 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.
authors.affiliation: Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA 90024-1759, USA. afl@ucla.edu
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Leuchter
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cook
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Marangell
authors.forename: William S
authors.initials: WS
authors.lastname: Gilmer
authors.forename: Karl S
authors.initials: KS
authors.lastname: Burgoyne
authors.forename: Robert H
authors.initials: RH
authors.lastname: Howland
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Sidney
authors.initials: S
authors.lastname: Zisook
authors.forename: Rakesh
authors.initials: R
authors.lastname: Jain
authors.forename: James T
authors.initials: JT
authors.lastname: McCracken
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Dan
authors.initials: D
authors.lastname: Iosifescu
authors.forename: Scott
authors.initials: S
authors.lastname: Greenwald
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D015283:Citalopram / Q000031:analogs & derivatives / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004569:Electroencephalography / Q000379:methods*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D011985:Receptors, Serotonin / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015283:Citalopram; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C046304:desmethylcitalopram