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-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.

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