Psychiatry Research, 2024, 342, 116165.
EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial
Christine Ulkea, Jürgen Kayserb,k, Craig E Tenkeb,k, Roland Merglc, Christian Sandera, Lidia YX Panierk, Jorge E Alvarengak, Maurizio Favad, Patrick J McGrathb, Patricia J Deldine, Melvin G McInnisf, Madhukar H Trivedig, Myrna M Weissmanb,k, Diego A Pizzagallih, Ulrich Hegerli,j, Gerard E Bruderb,k
aDepartment of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Germany; b Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; c Institute of Psychology, University of the Bundeswehr Munich, Munich, Germany; d Depression Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA; e Departments of Psychology and Psychiatry, The University of Michigan, Ann Arbor, MI, USA; f Department of Psychiatry, The University of Michigan, Ann Arbor, Michigan, USA; g Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas, USA; h Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, USA; i Research Center of the German Depression Foundation, Leipzig, Germany; j Department of Psychiatry, Psychosomatics and Psychotherapy, Goethe-University Frankfurt, Germany; k New York State Psychiatric Institute, New York, NY, USA
Received 24 March 2024; revised 27 August 2024; accepted 29 August 2024; published online 23 Sep 2024.
Abstract
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.
Key Words: MDD; EMBARC; Brain arousal; Arousal stability; Sertraline