Vagus Nerve Stimulation for Depression

Overseen By Kathryn Vera

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Disqualifiers: Schizophrenia, Psychosis, Substance use, others

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

Compensation: Varies

Number of Visits: 3

144 Participants Needed

Trial Summary

What is the purpose of this trial?

The acute and chronic effects of VNS stimulation on various on the autonomic nervous, cardiovascular, immune, and metabolic systems will be compared from noninvasive and minimally invasive physiological recordings and blood draws at various time points throughout the study. These interventions and assessments will be performed in individuals 18 years of age and older who are implanted with a VNS device, which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. The REVEAL study is not a treatment study; its primary objective is to scientifically investigate the contributing roles of efferent versus afferent vagus nerve modulation of multiple peripheral organs and their dependence on stimulation parameters, in which participants are those who have been implanted with a VNS device be receive standard of care treatment for their epilepsy or depressive disorder.

Will I have to stop taking my current medications?

No, you won't have to stop taking your current medications. The trial requires that your medication use is stable for two months before joining and remains stable during the study.

What data supports the effectiveness of the treatment Vagus nerve stimulation device for depression?

Research shows that vagus nerve stimulation (VNS) can help people with treatment-resistant depression, with studies reporting significant improvements in depression symptoms and higher response rates compared to standard treatments alone. Some patients experience benefits after 6-12 months, and long-term use has been associated with better quality of life and cognitive function. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for treating depression?

Vagus nerve stimulation (VNS) has been generally well-tolerated in studies, with many patients continuing treatment despite some side effects. While some adverse events have been reported, they are often manageable, and serious issues are rare. VNS does not have the systemic side effects associated with drug therapies, and it can be combined with antidepressant medications without causing drug interactions. ^{2 3 6 7 8}

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

Vagus nerve stimulation (VNS) is unique because it involves a device implanted in the chest that sends electrical impulses to the brain via the vagus nerve, which can help regulate mood. Unlike medications, VNS does not have systemic side effects and can be combined with antidepressant drugs without interactions. It is particularly beneficial for patients with treatment-resistant depression, offering long-term improvement and maintenance of mood stability. ^{4 8 9 10 11}

Research Team

John Osborn, PhD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults over 18 with drug-resistant epilepsy or major depressive disorder who already have a vagus nerve stimulation (VNS) device implanted. They must be able to consent, have stable medication use for two months prior, and possess active health insurance. Women of childbearing potential must agree to use birth control during the study.

Inclusion Criteria

I have major depression and already have a VNS device implanted.

I can sign and understand the consent form and HIPAA authorization.

My medication use has been stable for 2 months and I can keep it steady during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline measurements of autonomic nervous, cardiovascular, immune, and metabolic systems are taken

1 week

1 visit (in-person)

VNS Stimulation

Participants undergo Vagus Nerve Stimulation with various frequency orders to assess effects on multiple physiological parameters

12 weeks

Multiple visits (in-person and virtual) for assessments

Follow-up

Participants are monitored for changes in physiological parameters after the stimulation period

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Vagus nerve stimulation device

Trial Overview The REVEAL study investigates how different VNS settings affect the body's nerves, heart, immune system, and metabolism in patients with epilepsy or depression. It's not a treatment but aims to understand how efferent versus afferent nerve signals influence organ function based on VNS parameters.

Participant Groups

Group I: Order 6 assignment Experimental Treatment 1 Intervention

individuals 18 years of age and older who are implanted with a VNS device (standard of care), which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. Frequency order: F3=30Hz, F2=10Hz, F1=1Hz, period 1,2 and 3 respectively

Group II: Order 5 assignment Experimental Treatment 1 Intervention

individuals 18 years of age and older who are implanted with a VNS device (standard of care), which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. Frequency order: F2=10Hz, F1=1Hz, F3=30Hz, period 1,2 and 3 respectively

Group III: Order 4 assignment Experimental Treatment 1 Intervention

individuals 18 years of age and older who are implanted with a VNS device (standard of care), which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. Frequency order: F1=1Hz, F3=30Hz, F2=10Hz, period 1,2 and 3 respectively

Group IV: Order 3 assignment Experimental Treatment 1 Intervention

individuals 18 years of age and older who are implanted with a VNS device (standard of care), which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. Frequency order: F3=30Hz, F1=1Hz, F2=10Hz, period 1,2 and 3 respectively

Group V: Order 2 assignment Experimental Treatment 1 Intervention

individuals 18 years of age and older who are implanted with a VNS device (standard of care), which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. Frequency order: F2=10Hz, F3=30Hz, F1=1Hz, period 1,2 and 3 respectively

Group VI: Order 1 assignment Experimental Treatment 1 Intervention

individuals 18 years of age and older who are implanted with a VNS device (standard of care), which consists of patients who have been diagnosed with drug resistant epilepsy or major depressive disorder. Frequency order: F1=1Hz, F2=10Hz, F3=30Hz, period 1,2 and 3 respectively

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

In a one-year study of 6 patients with treatment-resistant depression, vagus nerve stimulation (VNS) therapy showed a significant increase in response rates from 40% at 3 months to 86% after 1 year, indicating that VNS efficacy improves over time.

The most common side effects reported were voice alteration in 86% of patients and headaches in 40%, suggesting that while VNS is generally safe, patients should be monitored for these specific adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation For Treatment Resistant Depression: Case Series Of Six Patients - Retrospective Efficacy And Safety Observation After One Year Follow Up. Kucia, K., Merk, W., Zapalowicz, K., et al.[2022]

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]

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]

Invasive vagus nerve stimulation (VNS) is a long-term treatment option for chronic and treatment-resistant depression, showing a significant cumulative response rate of 67.6% after 5 years when combined with standard treatment, compared to 40.9% for standard treatment alone.

VNS is generally safe, with hoarseness being the most common side effect, and it may improve depression severity, quality of life, and cognitive function, potentially through mechanisms like increased monoaminergic transmission and anti-inflammatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus Nerve Stimulation (VNS) in Depression]. Kavakbasi, E., Baune, BT.[2023]

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]

A systematic review of two randomized sham-controlled studies involving 255 participants found no significant difference in depression scores between vagus nerve stimulation (VNS) and sham treatment, suggesting limited efficacy of VNS for depression.

The review highlighted a marginal improvement in one depression rating scale (Beck Depression Inventory) with VNS, but overall, the efficacy and safety of VNS for treating depression remain unclear, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation for Depression: A Systematic Review. Lv, H., Zhao, YH., Chen, JG., et al.[2020]

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., et al.[2019]

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]

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 treatment for treatment-resistant depression, showing a unique ability to maintain remission in patients with severe and chronic forms of depression, including both unipolar and bipolar types.

Despite its potential, VNS has not been widely adopted in clinical practice, particularly in France, due to factors such as a lack of awareness among psychiatrists about surgical options, previous methodological challenges in early trials, and the need for multidisciplinary teams for implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation and depression]. Senova, S., Rabu, C., Beaumont, S., et al.[2019]

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]

References

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

Vagus Nerve Stimulation For Treatment Resistant Depression: Case Series Of Six Patients - Retrospective Efficacy And Safety Observation After One Year Follow Up. [2022]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

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

[Vagus Nerve Stimulation (VNS) in Depression]. [2023]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation for Depression: A Systematic Review. [2020]

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

Adverse events in children receiving intermittent left vagal nerve stimulation. [2019]

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

Vagus Nerve Stimulation for Major Depressive Episodes. [2015]

9. 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]

10. France pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation and depression]. [2019]

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

Vagus nerve stimulation for severe depression. [2019]