Preliminary Findings from LivaNova’s RECOVER Clinical Study on VNS Therapy for Treatment-Resistant Depression

June 17, 2024

Written by Joao L. de Quevedo, MD, PhD

LivaNova PLC, a leading medical technology company, recently released preliminary results from its RECOVER clinical study. The study evaluates the efficacy of Vagus Nerve Stimulation (VNS) Therapy in patients with treatment-resistant unipolar depression. Although the study did not meet its primary endpoint, it revealed promising results in secondary outcomes.

The primary endpoint focused on the difference in response rates measured by the Montgomery–Åsberg Depression Rating Scale (MADRS) between the active VNS Therapy and sham groups. Despite significant improvements from baseline in the active treatment group, an unexpectedly strong response in the sham group prevented the study from achieving statistical significance in the primary endpoint. However, specific secondary endpoints demonstrated statistically significant and clinically meaningful benefits for those receiving active VNS Therapy.

Dr. Charles R. Conway, Principal Investigator of the RECOVER study and Director of the Washington University in St. Louis Resistant Mood Disorders Center, emphasized the severity of unipolar depression in the study’s patient population and the lack of alternative treatments. The positive secondary outcomes provide hope for some patients who have not responded to other therapies, highlighting VNS Therapy’s potential role in addressing this unmet need.

LivaNova is conducting an in-depth analysis of the study data to determine the future direction of VNS Therapy for unipolar depression. The company plans to publish detailed findings in peer-reviewed journals later this year. It will continue its dialogue with the U.S. Centers for Medicare and Medicaid Services (CMS) about coverage for VNS Therapy.

Initiated in September 2019, the RECOVER study is the largest randomized clinical trial, involving up to 1,000 patients across the United States. It aims to evaluate the safety and effectiveness of VNS Therapy as an adjunctive treatment for patients with treatment-resistant unipolar and bipolar depression.

Despite not achieving its primary endpoint, the RECOVER study’s preliminary results offer promising insights into the potential benefits of VNS Therapy for patients with severe, treatment-resistant unipolar depression. LivaNova remains committed to exploring this therapy’s full potential and providing new treatment avenues for those in need.

Trial registration: Identifier NCT03887715.

Keywords: Electroconvulsive therapy (ECT); Esketamine; Ketamine; RECOVER trial; Transcranial magnetic stimulation (TMS); Treatment-resistant depression (TRD); Vagus nerve stimulation (VNS).

Reference: Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report. Conway CR, Aaronson ST, Sackeim HA, Duffy W, Stedman M, Quevedo J, Allen RM, Riva-Posse P, Berger MA, Alva G, Malik MA, Dunner DL, Cichowicz I, Luing H, Zajecka J, Nahas Z, Mickey BJ, Kablinger AS, Kriedt CL, Bunker MT, Lee YL, Shy O, Majewski S, Olin B, Tran Q, Rush AJ. Brain Stimul. 2024 Mar-Apr;17(2):448-459. Doi: 10.1016/j.brs.2024.03.016. Epub 2024 Apr 2. PMID: 38574853


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