Management of Major Depressive Disorder (MDD) might be improved by a biomarker to predict whether a selected medication is likely to lead to remission. We previously reported on a quantitative electroencephalogram-based biomarker, the Antidepressant Treatment Response (ATR) index, that integrated recordings at baseline and after one week of treatment. The present study prospectively tested whether treatment directed by the biomarker increased the likelihood of remission; we hypothesized that continued treatment with a drug predicted to lead to remission (i.e., high ATR values) would be associated with better outcomes than if the drug was predicted not to lead to remission (i.e., low ATR values). We enrolled 180 adult outpatients with unipolar MDD from the community. After one week of escitalopram treatment to determine the biomarker, stratified randomization (high vs. low ATR) was used to assign subjects to either continued escitalopram or a switch to bupropion as a blinded control condition, for seven additional weeks. For the 73 evaluable subjects assigned to continued escitalopram treatment, the remission rate was significantly higher for those in whom ATR had predicted remission versus non-remission (60.4% vs. 30.0%, respectively, p = 0.01). Accuracy was enhanced by combining 1-week depressive symptom change with ATR (68.6% vs 28.9%). This prospective validation study supports further development of the ATR biomarker, alone or together with early symptom change, to improve care by identifying individuals unlikely to remit with their current treatment, and support the decision to change treatment after one week rather than after failing a full, prolonged course of medication.

Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

Management of Major Depressive Disorder (MDD) might be improved by a biomarker to predict whether a selected medication is likely to lead to remission. We previously reported on a quantitative electroencephalogram-based biomarker, the Antidepressant Treatment Response (ATR) index, that integrated recordings at baseline and after one week of treatment. The present study prospectively tested whether treatment directed by the biomarker increased the likelihood of remission; we hypothesized that continued treatment with a drug predicted to lead to remission (i.e., high ATR values) would be associated with better outcomes than if the drug was predicted not to lead to remission (i.e., low ATR values). We enrolled 180 adult outpatients with unipolar MDD from the community. After one week of escitalopram treatment to determine the biomarker, stratified randomization (high vs. low ATR) was used to assign subjects to either continued escitalopram or a switch to bupropion as a blinded control condition, for seven additional weeks. For the 73 evaluable subjects assigned to continued escitalopram treatment, the remission rate was significantly higher for those in whom ATR had predicted remission versus non-remission (60.4% vs. 30.0%, respectively, p = 0.01). Accuracy was enhanced by combining 1-week depressive symptom change with ATR (68.6% vs 28.9%). This prospective validation study supports further development of the ATR biomarker, alone or together with early symptom change, to improve care by identifying individuals unlikely to remit with their current treatment, and support the decision to change treatment after one week rather than after failing a full, prolonged course of medication.

Sleep disturbance and short sleep duration are associated with inflammation and related disorders including cardiovascular disease, arthritis, diabetes mellitus, and certain cancers. This study was undertaken to test the effects of experimental sleep loss on spontaneous cellular inflammation and activation of signal transducer and activator of transcription (STAT) family proteins, which together promote an inflammatory microenvironment. In 24 healthy adults (16 females; 8 males), spontaneous production of IL-6 and TNF-α in monocytes and spontaneous intranuclear expression of activated STAT1, STAT3, and STAT5 in peripheral blood mononuclear cells (PBMC), monocyte-, and lymphocyte populations were measured in the morning after uninterrupted baseline sleep, partial sleep deprivation (PSD, sleep period from 3a.m. to 7a.m.), and recovery sleep. Relative to baseline, spontaneous monocytic expression of IL-6 and TNF-α was significantly greater after PSD (P<0.02) and after recovery sleep (P<0.01). Relative to baseline, spontaneous monocytic expression of activated STAT1 and STAT5 was significantly greater after recovery sleep (P<0.007 and P<0.02, respectively) but not STAT3 (P=0.09). No changes in STAT1, STAT3, or STAT5 were found in lymphocyte populations. Sleep loss induces activation of spontaneous cellular innate immunity and of STAT family proteins, which together map the dynamics of sleep loss on the molecular signaling pathways that regulate inflammatory and other immune responses. Treatments that target short sleep duration have the potential to constrain inflammation and reduce the risk for inflammatory disorders and some cancers in humans.