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ATR index may predict treatment-related remission in MDD

Key clinical point: Antidepressant Treatment Response (ATR) index biomarker may be effective for the prediction of therapy-related remission in patients with major depressive disorder (MDD).

Major finding: The remission rate was significantly higher in patients treated with escitalopram in whom ATR had predicted remission vs. no remission (60.5% vs. 30.0%; P = .010). The predictor equation was stronger with ATR index plus 1-week depressive symptom change vs. ATR alone (68.6% vs. 28.9%; P = .003).

Study details: In this PRISE-MD trial, patients with MDD received an initial week of single-blind escitalopram to determine ATR index biomarker and were then randomly assigned to either continued escitalopram (n = 73) or a switch to bupropion (n = 56) for 7 weeks.

Disclosures: This study was supported by grant from the U.S. National Institute of Mental Health, and access to the ATR system was provided at no cost by Aspect Medical Systems (now a division of Covien). The presenting author reported receiving research support from Covidien, National Institutes of Health, and NeoSync, Inc.


“As illustrated by the STAR*D trial, achieving remission for major depression (MDD) usually requires more than one 8-week treatment trial. Thus, the time to reach remission is prolonged.

The PRISE-MD trial examined the utility of the Antidepressant Treatment Response (ATR) Index, a biomarker derived from a quantitative EEG (qEEG), in guiding an important treatment decision—whether to continue escitalopram or switch to bupropion in patients with MDD. An increase in the ATR index (ATR+) one week after beginning escitalopram predicted MDD remission from escitalopram in the previous BRITE-MD trial.

After a week of escitalopram, 2 groups of patients, ATR+ (increased ATR index) and ATR- (no increased ATR index), were each randomized to stay on escitalopram, or switch to bupropion. As hypothesized, to achieve remission ATR+ predicted that it was better to continue escitalopram. ATR- predicted that it was better to switch to bupropion. Test sensitivity was 74.3% and specificity was 55.3%. Positive predictive value was 60.5%. Negative predictive value was 70.0%. Overall accuracy was 64.4%.

Of particular note, change in the ATR index was independent of changes on depression scores. A hybrid model adding early symptom change to the ATR index improved accuracy further to 69.9%

The ATR index reflects a composite of alpha and theta waves in frontal leads, measured by QEEG. QEEG digitizes EEG waves, quantifying the frequency components (alpha, beta, theta, etc). Leuchter et al (2015) proposed that ATR reflects communication between the prefrontal areas (including the anterior cingulate) and the thalamic dorsomedial nucleus. Thalamocortical communication is hypothesized to be disrupted in major depression. If so, an increased ATR index detects early antidepressant effects on thalamocortical communication taking place before depressive symptoms overtly decrease.

Assuming that a multi-site study confirms its effectiveness, the ATR index, measured with a few EEG electrodes in ten minutes, holds considerable promise for improving depression treatment.”

Gita Ramamurthy, MD

Director, Psychiatry Consultation-Liaison Service


Cook IA et al. J Psychiatr Res. 2020 Feb 26. doi: 10.1016/j.jpsychires.2020.02.028.