An interventional study of Vagus Nerve Stimulation (VNS) in Treatment Resistant Depression, sponsored by LivaNova. Recruiting at 101 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by LivaNova · Not applicable, Interventional, and Treatment
Objectives of this study are to determine whether active VNS Therapy treatment is superior to a no stimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization.
A prospective, multi-center, randomized, controlled, blinded trial of subjects implanted with VNS Therapy. Active treatment and no stimulation control are randomized, at least two weeks after implantation and observed for 12-months.
After completing the 12 month endpoint in the RCT portion of the study, all RECOVER subjects will transition into the prospective, open-label, longitudinal portion of the study. Subjects in the control arm of RECOVER will be activated after completing the 12 month endpoint.
After completion of enrollment in the RCT portion or meeting of interim success criterion (whichever comes first), up to 5,800 new subjects may enroll directly into the open-label,prospective, longitudinal study. These subjects will participate in the study for approximately 5 years.
The study has been designed in accordance with The Centers for Medicare and Medicaid Services coverage with evidence development (CED) decision entitled "Decision Memo for Vagus Nerve Stimulation (VNS) for Treatment Resistant Depression (TRD) (CAG-00313R2).
448 studies on the registry are indexed under Depressive Disorder, Treatment-Resistant; 147 are open to participants now.
This study's planned enrollment of 6,800 is above the median of 59 across 372 interventional studies indexed under Depressive Disorder, Treatment-Resistant.
Browse Depressive Disorder, Treatment-Resistant studies →LivaNova is the lead sponsor of 40 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
The patient must be in a major depressive disorder (MDD) episode for ≥ two years or have had at least four episodes of MDD, including the current episode.
The patient's depressive illness meets a minimum criterion of four prior failed treatments of adequate dose and duration as measured by a tool designed for this purpose.
The patient is experiencing a major depressive episode (MDE) as measured by a guideline recommended depression scale assessment tool on two visits, within a 45-day span prior to implantation of the VNS device.
Patients must maintain a stable medication regimen for at least four weeks before device implantation.
Exclusion Criteria:
Current or lifetime history of psychotic features in any MDE;
Current or lifetime history of schizophrenia or schizoaffective disorder;
Current or lifetime history of any other psychotic disorder;
Current or lifetime history of rapid cycling bipolar disorder;
Current secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder;
Current suicidal intent; or
Treatment with another device or investigational drugs.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Group will have VNS activated 2 weeks post implant.
Device: Vagus Nerve Stimulation (VNS)
Group will be implanted with VNS but device is not activated for the first 12 months. After 12 months, this group can receive stimulation.
Device: Vagus Nerve Stimulation (VNS)
VNS is an implantable device that delivers stimulation to the vagal nerve.
Also known as: VNS
Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Response
The rate of response defined as person months of response/total months of study participation where response is at least a 50% reduction from baseline in MADRS total score. Subjects discontinuing the study before the endpoint assessment will be considered as non-responders for each successive month after discontinuance.
Time frame: 12 months post randomization
Montgomery Åsberg Depression Rating Scale (MADRS) Time to First response
Time from randomization to the first observed MADRS response.
Time frame: Baseline up to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Time to First Remission
Time from randomization to the first observed MADRS remission.
Time frame: Baseline up to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Response
Duration of MADRS response, defined as the number of consecutive months from first observed MADRS response to the first assessment of MADRS response relapse.
Time frame: Baseline up to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Rate of Remission
The rate of remission is defined as total number of months in remission divided by total months of expected study participation. Subjects discontinuing the study before the endpoint assessment will be considered as non-in-remission for each successive month after discontinuance
Time frame: Baseline up to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Response
Maximum duration of MADRS response, defined as the maximum number of consecutive months in response (only for subjects experiencing MADRS response).
Time frame: Baseline up to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Duration of Remission
Duration of MADRS remission, defined as the number of consecutive months from first observed MADRS remission to the first assessment of MADRS remission relapse (defined score \> 20).
Time frame: Baseline up to 12 Months
Montgomery Åsberg Depression Rating Scale (MADRS) Maximum duration of Remission
Maximum duration of MADRS remission, defined as the maximum number of consecutive months in remission (only for subjects experiencing MADRS remission).
Time frame: Baseline up to 12 Months
Assess all Adverse Events
All adverse events, with a focus on device or procedure-related serious adverse events.
Time frame: Implant to 12 Months
WHO Disability Assessment Schedule (WHODAS) Changes in scores over time
Time frame: Baseline to 12 Months
Health Outcome Scale (EQ-5D-L) Changes in scores over time
Time frame: Baseline to 12 Months
Clinical Global Impressions Scale - Improvement (CGI-I) Response
A CGI-I score ≤ 2 at 12 months from randomization. Subjects discontinuing the study before the 12 months assessment will be considered as not in response for each successive month after discontinuance.
Time frame: 12 months post randomization
Sheehan Suicidality Tracking Scale (S-STS) Changes in Suicidality
Suicide attempts as measured by items #10 \& #12 in S-STS scale
Time frame: Implant to 12 Months
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Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Depressive Disorder, Treatment-Resistant →