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Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report.

Charles R Conway, Scott T Aaronson, Harold A Sackeim, Walter Duffy, Mary Stedman, João Quevedo, Rebecca M Allen, Patricio Riva-Posse, Matthew A Berger, Gustavo Alva, Mohd Azfar Malik, David L Dunner, Ivan Cichowicz, Heather Luing, John Zajecka, Ziad Nahas, Brian J Mickey, Anita S Kablinger, Christopher L Kriedt, Mark T Bunker, Ying-Chieh Lisa Lee, Olivia Shy, Shannon Majewski, Bryan Olin, Quyen Tran, A John Rush

Brain Stimulation 2024 DOI: 10.1016/j.brs.2024.03.016 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized sham-controlled trial (baseline description of qualified vs. not qualified participants) Peer reviewed
Sample size 493
Population Unipolar major depressive disorder patients who qualified for the RECOVER trial
Intervention vagus nerve stimulation
Topics Esketamine Depression
Keywords Electroconvulsive therapy Recover trial Treatment-resistant depression trd Therapy-resistant depression Refractory depression Integrated treatment Neuromodulation brain stimulation Tms Vns Antidepress
Citations 16
Registration NCT03887715
Key findings RECOVER-qualified unipolar patients had marked treatment resistance and disability, and most had failed one or more prior interventional psychiatric treatments, which were associated with earlier onset, more severe presentation, and greater treatment resistance.

Abstract

RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. 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. 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). 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. 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. ClinicalTrials.gov Identifier NCT03887715.

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Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
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Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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