EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial

Hyperstable arousal regulation during a 15-min resting electroencephalogram (EEG) has been linked to a favorable response to antidepressants. The EMBARC study, a multicenter randomized placebo-controlled clinical trial, provides an opportunity to examine arousal stability as putative antidepressant response predictor in short EEG recordings. We tested the hypothesis that high arousal stability during a 2-min resting EEG at baseline is related to better outcome in the sertraline arm and explored the specificity of this effect. Outpatients with chronic/recurrent MDD were recruited from four university hospitals and randomized to treatment with sertraline (n = 100) or placebo (n = 104). The change in the Hamilton Rating Scale for Depression (HRSD-17) was the main outcome. Patients were stratified into high and low arousal stability groups. In mixed-model repeated measures (MMRM) analysis HRSD-17 change differed significantly between arousal groups, with high arousal stability being associated with a better outcome in the sertraline arm, and worse outcome in the placebo arm at week 4, with moderate effect sizes. When considering both treatment arms, a significant arousal group x time x treatment interaction emerged, highlighting specificity to the sertraline arm. Although findings indicate that arousal stability is likely to be a treatment-specific marker of response, further out-of-sample validation is warranted.