VNS for Bipolar Depression

(RECOVER Trial)

Recruiting at 57 trial locations

Overseen By Mary L Stedman, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: LivaNova

Disqualifiers: Psychotic disorders, Schizophrenia, Bipolar, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

6800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing whether VNS Therapy, which sends electrical impulses to the vagus nerve, can reduce depression symptoms in patients who haven't responded to other treatments. The study will observe the effects of VNS therapy over a year. Vagus nerve stimulation (VNS) is a recognized treatment for severe treatment-resistant depression and has shown promising results.

Will I have to stop taking my current medications?

The trial requires that you maintain a stable medication regimen for at least four weeks before the device is implanted, so you should not stop taking your current medications.

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation (VNS) is generally considered safe for humans, with studies showing it is well-tolerated and has a low rate of serious side effects. Common side effects are related to the stimulation itself and can often be managed by adjusting the device. There are no adverse cognitive effects, and it can be used alongside other treatments without causing drug interactions. ^{1 2 3 4 5}

How does vagus nerve stimulation differ from other treatments for depression?

Vagus nerve stimulation (VNS) is unique because it involves a device that stimulates the vagus nerve, which is different from typical drug treatments. It is particularly used for severe depression that doesn't respond to standard treatments, and it works by potentially altering brain activity related to mood regulation. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Vagus Nerve Stimulation (VNS) Therapy System for depression?

Research shows that Vagus Nerve Stimulation (VNS) has been studied for over 20 years and may help people with severe, hard-to-treat depression. It has been approved for adults with treatment-resistant depression, and long-term studies suggest it can have an antidepressant effect. ^{4 6 9 10 11}

Who Is on the Research Team?

Charles Conway, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with treatment-resistant depression, which means they've tried at least four different treatments without success. They should be currently in a major depressive episode that's lasted for two years or more, or have had at least four episodes of major depression. Participants must not change their medications for four weeks before getting the VNS device and can't join if they have certain cognitive disorders, a history of rapid cycling bipolar disorder, schizophrenia, other psychotic disorders, or current suicidal thoughts.

Inclusion Criteria

Patients must maintain a stable medication regimen for at least four weeks before device implantation.

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.

I have been diagnosed with major depression twice in the last 45 days.

Exclusion Criteria

I have never had rapid cycling bipolar disorder.

I am not currently participating in another clinical trial for drugs or devices.

You have been diagnosed with schizophrenia or schizoaffective disorder at any point in your life.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation

Participants are implanted with the VNS Therapy device

2 weeks

Treatment

Active VNS Therapy treatment or no stimulation control for 12 months

12 months

Open-label extension

All subjects transition to open-label VNS Therapy, including control group activation

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VNS Therapy® System

Trial Overview The study is testing whether using Vagus Nerve Stimulation (VNS) as an additional treatment helps reduce symptoms of severe depression compared to no stimulation control after one year. Patients are randomly assigned to either receive active VNS Therapy or be part of the control group that does not receive stimulation.

How Is the Trial Designed?

Group I: Active Active Control 1 Intervention

Group will have VNS activated 2 weeks post implant.

Group II: Control Placebo Group 1 Intervention

Group will be implanted with VNS but device is not activated for the first 12 months. After 12 months, this group can receive stimulation.

Who Is Running the Clinical Trial?

LivaNova

Lead Sponsor

Trials

66

Recruited

31,100+

Vladimir A. Makatsaria

LivaNova

Chief Executive Officer since 2024

Bachelor of Arts in Physiology, Master of Healthcare Administration, and Master of Business Administration from the University of Minnesota

Dr. Deanna Wilke

LivaNova

Chief Medical Officer since 2023

MD from Harvard Medical School

Published Research Related to This Trial

Vagus Nerve Stimulation (VNS) has shown promising long-term antidepressant effects when combined with standard treatment in over 1100 patients with difficult-to-treat depression, particularly after 12 months of stimulation.

A recent randomized trial did not show immediate benefits from VNS, suggesting that longer treatment durations are necessary to fully assess its efficacy and that new metrics are needed to evaluate clinically meaningful improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders. Sackeim, HA., Dibué, M., Bunker, MT., et al.[2022]

Vagus nerve stimulation (VNS) is a promising device-based therapy for treatment-resistant depression, which is a significant issue affecting both healthcare costs and patient well-being.

Understanding the initiation, implantation, and monitoring of VNS treatment is crucial for psychiatric nurses to improve care for patients suffering from this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for severe depression. Rado, J., Janicak, PG.[2019]

Vagus nerve stimulation (VNS) therapy is FDA-approved for treatment-resistant depression in adults and has shown long-term antidepressant effects based on clinical studies.

The paper also explores the potential use of VNS therapy for treatment-resistant depression in adolescents and children, indicating its broader applicability beyond just adult patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: can it be used in adolescents or children with treatment-resistant depression? Yu, ZJ., Weller, RA., Sandidge, K., et al.[2021]

Vagus Nerve Stimulation (VNS) has been used since the 1990s as an effective treatment for epilepsy, and emerging data suggest it may also be beneficial for treatment-resistant depression due to its connections to brain areas that regulate mood.

PET studies indicate that VNS induces functional changes in brain regions associated with affect, providing insight into its potential mechanisms of action as an antidepressant, although further research is needed to confirm its efficacy and specific uses in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation. A potential therapy for chronic/recurrent depression?]. Rush, AJ., Linden, M., Zobel, A.[2006]

A systematic review of 14 studies found that vagus nerve stimulation (VNS) showed a significant reduction in depression scores and a 31.8% response rate in uncontrolled studies, indicating potential efficacy.

However, a randomized control trial with 235 patients found no significant difference between VNS and placebo, suggesting that the positive results in earlier studies may be influenced by a placebo effect rather than true therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs. Martin, JL., Martín-Sánchez, E.[2022]

In a study of 11 patients with chronic treatment-resistant depression, vagus nerve stimulation therapy led to significant reductions in depression scores over one year, with response and remission rates of 55% and 27%, respectively.

While the therapy showed promise in improving mood, it was associated with common and sometimes severe side effects, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. Corcoran, CD., Thomas, P., Phillips, J., et al.[2019]

In a study of 15 patients with treatment-resistant depression, vagus nerve stimulation (VNS) significantly reduced depression scores over 12 months, with a mean Beck Depression Inventory score dropping from 37.8 to 24.6, indicating a positive treatment effect.

By the end of the year, 28.6% of patients showed a response to VNS, and 7.1% achieved remission, with side effects like hoarseness and nausea being common but not leading to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. Cristancho, P., Cristancho, MA., Baltuch, GH., et al.[2012]

Vagus nerve stimulation (VNS) is an effective treatment for major depressive episodes, showing a symptomatic response in 15-17% of patients after 10 weeks and 22-37% after 12 months, with remission rates of 15-17% after a year.

VNS is well-tolerated with high continuation rates (90-98%) and low adverse event-related discontinuations (3%), and it does not produce systemic side effects like traditional antidepressants, making it a safe alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation for Major Depressive Episodes. Eljamel, S.[2015]

In a retrospective study of 62 patients treated with vagus nerve stimulation (VNS) for epilepsy, only 6 patients experienced significant seizure reduction, indicating that while VNS can be beneficial, it may not be effective for the majority of patients.

Contrary to its reputation for low adverse effects, the study found that only 9 patients had no adverse effects, with some experiencing severe and even life-threatening complications, highlighting the need for careful monitoring throughout the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation therapy in epilepsy patients: long-term outcome and adverse effects: a retrospective analysis]. Carius, A., Wintermantel, A.[2022]

Vagus nerve stimulation (VNS) is being explored as a treatment for major depression that does not respond to traditional medications, although its exact mechanism of action is still unclear.

This review examines preclinical studies of VNS in relation to two key theories of depression: the monoaminergic hypothesis, which focuses on neurotransmitters, and the neural plasticity hypothesis, which emphasizes the brain's ability to adapt and change.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant mechanism of action of vagus nerve stimulation: Evidence from preclinical studies. Grimonprez, A., Raedt, R., Baeken, C., et al.[2021]

Vagus nerve stimulation (VNS) is a promising treatment for intractable epilepsy and severe depression, providing a reliable option for patients who do not respond to traditional therapies, with mild to moderate side effects that can often be managed by adjusting the device.

Approximately 50% of epilepsy patients achieve satisfactory treatment with monotherapy, and this rate increases to 75% with polytherapy; however, about one-third of patients remain refractory to all treatments, highlighting the need for alternative approaches like VNS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation. Ekmekçi, H., Kaptan, H.[2020]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for severe depression. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: can it be used in adolescents or children with treatment-resistant depression? [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation. A potential therapy for chronic/recurrent depression?]. [2006]

5. England pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. [2012]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation for Major Depressive Episodes. [2015]

9. Germany pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation therapy in epilepsy patients: long-term outcome and adverse effects: a retrospective analysis]. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

The antidepressant mechanism of action of vagus nerve stimulation: Evidence from preclinical studies. [2021]

11. North Macedonia pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation. [2020]