Durability of the benefit of vagus nerve stimulation in markedly treatment-resistant major depression: a RECOVER trial report.
Charles R Conway, Augustus John Rush, Scott T Aaronson...
https://pubmed.ncbi.nlm.nih.gov/41529263/Actively Recruiting
Led by LivaNova · Updated on 2026-06-15
6800
Participants Needed
101
Research Sites
148 weeks
Total Duration
Researchers are evaluating the safety and effectiveness of the Vagus Nerve Stimulation VNS Therapy System as an additional treatment for people with treatment-resistant depression. This prospective, multi-center, randomized, controlled, and blinded trial compares active VNS therapy to a no stimulation control group in reducing depressive symptoms over 12 months. The study follows guidelines aligned with Medicare and Medicaid coverage decisions for VNS in this condition. Participants receive an implant of the VNS device and are randomized at least two weeks after implantation to either have the device activated or remain without stimulation for the first 12 months. After this initial period, those in the control group can begin stimulation. Following the 12-month randomized phase, all participants enter an open-label, longitudinal study lasting about five years, including new enrollees after the initial trial phase. During the study, participants are monitored through various depression rating scales, including the Montgomery sberg Depression Rating Scale MADRS, to assess response and remission rates up to 12 months. Safety is tracked by recording adverse events from implantation through the first year. Additional assessments include disability and health outcome scales, as well as suicidality tracking. The study aims to gather long-term data on treatment effects and participant well-being.
CONDITIONS
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
L
Laura Yates, BSN
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LivaNova
Lead Sponsor
This table compares participation in this trial with other options available for this condition. The information is drawn from published research and the trial’s study details and is provided for educational purposes only.
| Factors | Vagus Nerve Stimulation (Active) | No Stimulation (Sham Control) |
|---|---|---|
| What it is | An implanted device that delivers regular electrical stimulation to the vagus nerve, intended to modulate brain networks involved in depression. | An identical implanted device that is not activated, serving as a sham (placebo) control with no active vagus nerve stimulation. |
| Role in this trial | Tests whether active VNS Therapy can reduce depression severity or improve clinical outcomes in patients who have not responded to other treatments. | Serves as a control to distinguish the effects of surgery and device implantation from the effects of active vagus nerve stimulation. |
| Primary use or procedure | Delivers intermittent electrical impulses to the vagus nerve as adjunctive therapy to standard medication in people with treatment-resistant depression. | Participants have the VNS device implanted but do not receive active nerve stimulation. They continue with their stable medication regimen. |
| How it is given or performed | The VNS Therapy System is surgically implanted, and after recovery, is activated to deliver scheduled electrical impulses to the left vagus nerve in the neck. | The device is surgically implanted but remains inactive, so no stimulation is delivered to the nerve. |
| Evidence status as of recent RECOVER trial analyses | Prior RECOVER trial publications report that among participants with marked treatment-resistant depression, VNS Therapy has shown sustained improvement in depressive symptoms and durable clinical benefit over long-term follow-up. | Sham control arms in device studies are designed as comparators; there are no long-term outcome benefits expected with an inactive device. |
| Important limitations | Surgical implantation poses operative risks. VNS Therapy may not be effective for all and some questions remain on predictors of who benefits most. | Undergoes same surgical implantation as active arm but does not receive active stimulation, so benefits are not expected beyond placebo or procedural effects. |
Disclaimer: This comparison is created with the help of artificial intelligence(AI) and may contain errors or missing information. It is not medical advice and does not mean one option is better or safer than another. Clinical trials are still being studied, and joining a trial is your choice. Please consult your healthcare professional before making any decisions.
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Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Duration - 12 months
Participants undergo implantation of the VNS device and are randomized to either have the device activated about two weeks after implantation or have the device implanted but not activated for 12 months. The treatment phase lasts 12 months.
Regular visits during 12 months
Duration - Approximately 5 years
After completing the initial 12-month randomized phase, all participants enter an open-label, prospective study where stimulation is provided. New participants may also join this phase and will be followed for about 5 years.
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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Charles R Conway, Augustus John Rush, Scott T Aaronson...
https://pubmed.ncbi.nlm.nih.gov/41529263/Vasilis C Hristidis, Victoria De Leon, Andrew D Van Der Vaart...
https://pubmed.ncbi.nlm.nih.gov/42447264/Charles R Conway, Scott T Aaronson, Harold A Sackeim...
https://pubmed.ncbi.nlm.nih.gov/38574853/Scott T Aaronson, Charles R Conway, Charles Gordon...
https://pubmed.ncbi.nlm.nih.gov/40673907/Victoria C de Leon, Rebecca M Allen, João Quevedo...
https://pubmed.ncbi.nlm.nih.gov/39722333/LivaNova
Lead Sponsor