EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial
- PMID: 39316999
- DOI: 10.1016/j.psychres.2024.116165
EEG measures of brain arousal in relation to symptom improvement in patients with major depressive disorder: Results from a randomized placebo-controlled clinical trial
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.
Keywords: Arousal stability; Brain arousal; EMBARC; MDD; Sertraline.
Copyright © 2024. Published by Elsevier B.V.
Conflict of interest statement
Declaration of competing interest In the last three years, the authors report the following financial disclosures, for activities unrelated to the current research: Dr. Hegerl: Dr. Hegerl was an advisory board member for Lilly, Lundbeck, Servier, Takeda and Otsuka; a consultant for Bayer and Nycomed; and a speaker for Bristol-Myers Squibb, Medice Arzneimittel, Novartis, and Roche. Dr. Fava: Dr. Fava reports the following lifetime disclosures: http://mghcme.org/faculty/faculty-detail/maurizio_fava. Dr. McInnis: Dr. McInnis received funding from the NIMH and consulting fees from Janssen and Otsuka Pharmaceuticals. Dr. Trivedi: Dr. Trivedi reports the following lifetime disclosures: research support from the Agency for Healthcare Research and Quality, Cyberonics Inc., National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Diabetes and Digestive and Kidney Diseases, Johnson & Johnson, and consulting and speaker fees from Abbott Laboratories Inc., Akzo (Organon Pharmaceuticals Inc.), Allergan Sales LLC, Alkermes, AstraZeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb Company, Cephalon Inc., Cerecor, Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals Inc., Forest Pharmaceuticals, GlaxoSmithKline, Health Research Associates, Johnson & Johnson, Lundbeck, MedAvante Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America Inc., MSI Methylation Sciences Inc., Nestle Health Science-PamLab Inc., Naurex, Neuronetics, One Carbon Therapeutics Ltd., Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd., Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. Dr. Weissman: Funding from NIMH, the National Alliance for Research on Schizophrenia and Depression (NARSAD), the Sackler Foundation, and the Templeton Foundation; royalties from the Oxford University Press, Perseus Press, the American Psychiatric Association Press, and MultiHealth Systems. Dr. Pizzagalli: Over the past 3 years, Dr. Pizzagalli has received consulting fees from Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Sage Therapeutics, Sama Therapeutics, and Takeda; he has received honoraria from the American Psychological Association, Psychonomic Society and Springer (for editorial work) and Alkermes; he has received research funding from the BIRD Foundation, Brain and Behavior Research Foundation, Millennium Pharmaceuticals, National Institute of Mental Health, and Wellcome Leap; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. No funding or any involvement from these entities was used to support the current work, and all views expressed are solely those of the authors. Dr. Kayser: funding from NIMH and the John F. Templeton foundation. All other authors report no financial conflicts.
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