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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how vagus nerve stimulation (VNS) affects different body systems in people with depression or drug-resistant epilepsy. It does not test a new treatment but studies how the VNS device (a medical device used to stimulate the vagus nerve) functions in those already using it. Participants should have a diagnosis of major depressive disorder or drug-resistant epilepsy and either already have or will receive a VNS device. This study suits those who have tried other treatments without success and are already receiving care with a VNS device. As an unphased trial, it offers participants the chance to contribute to a deeper understanding of VNS effects, potentially improving future treatment approaches.

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 prior data suggests that this VNS device is safe for individuals with drug resistant epilepsy or major depressive disorder?

Research has shown that vagus nerve stimulation (VNS) is generally safe for individuals with depression that hasn't improved with other treatments. In one study, only about one percent of participants discontinued VNS due to side effects, indicating that most can tolerate the treatment without major issues. While some side effects exist, they typically aren't severe enough to cause discontinuation. VNS has also been used for many years to treat epilepsy, further supporting its safety. Overall, evidence suggests that VNS is a safe option for many considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for major depressive disorder typically involve medications like SSRIs or SNRIs, which work by balancing neurotransmitters in the brain. However, vagus nerve stimulation (VNS) offers a unique approach. This treatment involves using a device to send electrical impulses to the vagus nerve, which is thought to influence mood-regulating areas of the brain. Researchers are excited about VNS because it provides an alternative for individuals who haven't found relief with traditional drug therapies, potentially offering a new avenue for managing depression without relying solely on medication. The ability to adjust stimulation frequencies also allows for personalized treatment, which could improve outcomes for those with treatment-resistant depression.

What evidence suggests that this VNS device is effective for depression?

Research has shown that stimulating the vagus nerve (VNS) can help people with depression that hasn't improved with other treatments. In this trial, participants will receive different frequency orders of VNS to evaluate its effectiveness. Studies have found that VNS can reduce symptoms in those who haven't had success with other methods. For instance, one study found that about 28.6% of patients felt better after a year of VNS, with some even seeing their symptoms disappear. Another study showed that VNS therapy worked better than usual treatments over five years. People with severe depression also reported feeling better with VNS. These findings suggest VNS could be a promising option for managing difficult-to-treat depression. ^{1 3 4 6 7}

Who Is on the Research Team?

John Osborn, PhD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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) 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]

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 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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/11682255/

Vagus nerve stimulation (VNS) for treatment-resistant ...

VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165032725004720

Characterizing the effects of vagus nerve stimulation on ...

A randomized sham-control trial of adjunctive VNS was conducted in 493 participants with markedly treatment-resistant MDD.

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/21295002/

Effectiveness and safety of vagus nerve stimulation for ...

By 1 year, 28.6% (n = 4) of the sample responded to VNS and 7.1% (n = 1) remitted according to the BDI. Secondary outcomes on the Hamilton Depression Rating ...

4.

psychiatryonline.org

psychiatryonline.org/doi/10.1176/appi.ajp.2017.16010034

A 5-Year Observational Study of Patients With Treatment ...

The registry results indicate that the adjunctive VNS group had better clinical outcomes than the treatment-as-usual group, including a significantly higher 5- ...

5.

medicine.washu.edu

medicine.washu.edu/news/vagus-nerve-stimulation-relieves-severe-depression/

Vagus nerve stimulation relieves severe depression

People with severe, treatment-resistant depression who received vagus nerve stimulation therapy showed improvement in depressive symptoms.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2990624/

Vagus Nerve Stimulation (VNS) and Treatment of Depression

One other positive from the trial was the favorable tolerability of VNS, with a withdrawal rate of only one percent due to adverse events. One Year Outcome With ...

7.

psychiatrist.com

psychiatrist.com/jcp/effectiveness-safety-vagus-nerve-stimulation-severe/

Effectiveness and Safety of Vagus Nerve Stimulation for ...

By 1 year, 28.6% (n = 4) of the sample responded to VNS and 7.1% (n = 1) remitted according to the BDI. Secondary outcomes on the Hamilton ...