Recent research aims at developing a biomarker to predict antidepressant treatment outcomes in major depressive disorder. The Antidepressant Treatment Response (ATR) index has been correlated with response to antidepressant medication (, ) but has not been assessed in a placebo-controlled trial. EEGs recorded at pretreatment baseline and after 1 week of randomized treatment were used to calculate ATR index for 23 subjects with major depressive disorder who were treated for 8 weeks with fluoxetine (FLX) 20 mg (n = 12) or placebo (n = 11). The 17-item Hamilton Depression Rating Scale (HamD17) assessed symptom severity; ATR index was assessed as a predictor of percent change in HamD17 score, endpoint response (≥ 50% improvement) and remission (HamD17 score ≤ 7). The ATR index was significantly associated with improvement on FLX (r = 0.64, P = 0.01), with a higher mean ATR index for FLX responders than for nonresponders (t(10) = -2.07, P = 0.03). Receiver operating characteristic analysis found a 0.83 area under the curve (P = 0.03), for ATR index as a predictor for FLX, while an optimized ATR index cutoff of 47.3 yielded 100% sensitivity, 66.7% specificity, 75% positive predictive value, and 100% negative predictive value. Importantly, ATR index did not correlate significantly with placebo outcomes. Results extend ATR index findings to include predictive validity with fluoxetine, suggesting that this biomarker has specificity for drug effects.