Abstract
Background: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention.
Objective: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine.
Methods: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE).
Results: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials.
Conclusions: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT.
Trial registration: ClinicalTrials.gov Identifier NCT03887715.
Keywords: Electroconvulsive therapy; Esketamine; RECOVER trial; Transcranial magnetic stimulation (TMS); Treatment-resistant depression (TRD); Vagus nerve stimulation (VNS).
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest MAB, BJM, and CLK have no conflicts of interest to declare. CRC has received research support from the American Foundation for Suicide Prevention, Assurex Health, August Busch IV Foundation, Barnes-Jewish Hospital Foundation, LivaNova, National Institute of Mental Health, and the Taylor Family Institute for Innovative Psychiatric Research; consulted for LivaNova and Sage Therapeutics; and was a part-time employee at the John Cochran VA Medical Center in St. Louis. STA is a consultant to Genomind, LivaNova, Janssen, Neuronetics, and Sage Therapeutics; and has received research support from Compass Pathways and Neuronetics. HAS serves as a scientific adviser and receives consulting fees from Cerebral Therapeutics, Holmusk Technologies, LivaNova, MECTA Corporation, Neurolief, Neuronetics, Parow Entheobiosciences, and SigmaStim; receives honoraria and royalties from Elsevier and Oxford University Press; is the inventor of non-remunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices, each held by the SigmaStim Corporation; and is also the originator of Magnetic Seizure Therapy (MST). WD has consulted for Corium and Abbott; and has been on the LivaNova Advisory Board. MS is a Principal Investigator for Cassava Sciences, Eisai, Lilly, and LivaNova. JQ received clinical research support from LivaNova; has speaker bureau membership with Myriad Neuroscience and AbbVie; consultant for Eurofarma; stockholder at Instituto de Neurociencias; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. RMA is one of the owners of a multi-site interventional psychiatry and clinical trials company, Seattle Neuropsychiatric Treatment Center; receives research funding from LivaNova and Compass Pathways; and previously received research funding from Alto Neuroscience. PR-P is a consultant for LivaNova, Janssen Pharmaceuticals, MotifNeuro, and Abbott Neuromodulation. GA receives Research Support from AbbVie, Accera, Axsome, Axovant, Biogen, Eisai, Eli-Lily, Neurotrope, Genentech, Intra Cellular, Janssen, Lundbeck, Neurim, Novartis, Otsuka, Roche, Sage, Suven, and Trans Tech; and is on the Speakers Bureau and Consultant for AbbVie, Acadia, Alkermes, Axsome, Biogen, Janssen, Idorsia, Lundbeck, Myriad, Neurocrine, Nestle, Otsuka, Sage, Sunovion, Teva and Takeda. MAM has received research support and/or speaker honoraria from Axsome, AbbVie, Alkermes, Intracellular, Janssen, Neurocrine, Otsuka, and Teva. DLD receives payment for clinical services for a former research patient from LivaNova; speaker for Janssen (esketamine nasal spray); and conducts forensic consultations, independent medical evaluations, and legal testimony for various firms. IC is co-owner of Mindful Behavioral Health, PLLC and receives speaker fees from Johnson and Johnson (Janssen). HL has received consulting and/or speaking fees from Alkermes, Axsome, Intracellular, Janssen, Karuna, Sage, and Teva; and conducts forensic consultations, independent medical evaluations, and legal testimony for various firms and co-owns Florida Center for TMS. JZ receives research support from Boehringer-Ingelheim, Compass Pathways, Hoffman-LaRoche, Johnson and Johnson (Janssen), LivaNova, Otsuka, Neurocrine Bioscience, and Sage Therapeutics; and received consulting fees from Alphasigma USA and Johnson and Johnson (Janssen). ZN is a consultant to LivaNova, Magnus Medical, and Motif; and has also received research support from LivaNova. ASK has received research support from Alto Neuroscience, Axial Therapeutics, BEAM Diagnostics, Curemark, Gilead Sciences, Liva Nova, and the National Institutes of Health. MTB is a former employee and a current consultant of LivaNova. Y-CL and OS are employees of LivaNova. SM, BO, and QT are employees of LivaNova and hold stock options. AJR has received consulting fees from Compass, Curbstone Consultant, Emmes, Evecxia Therapeutics, Holmusk Technologies, ICON, Johnson and Johnson (Janssen), LivaNova, MindStreet, Neurocrine Biosciences, Otsuka-US; speaking fees from LivaNova, Johnson and Johnson (Janssen), and Wolters Kluwer Health; royalties from Guilford Press and UT Southwestern Medical Center (for the Inventory of Depressive Symptoms and its derivatives); named co-inventor on US Patent 7,795,033 (Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS) and US Patent 7,906,283 (Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S).
