Vagus Nerve Stimulation for Depression

Recruiting in Palo Alto (17 mi)

Overseen by John Osborn, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Minnesota

Disqualifiers: Schizophrenia, Psychosis, Substance use, others

No Placebo Group

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.

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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.

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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.

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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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Minnesota Minneapolis, MN

Who Is Running the Clinical Trial?

University of Minnesota Lead Sponsor

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] One year observation and evaluation of the VNS (vagus nerve stimulation) efficacy and safety for patients with treatment resistant depression in Polish conditions.

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] To describe the outcomes of a consecutive series of depressed patients treated with vagus nerve stimulation (VNS) following US Food and Drug Administration (FDA) approval of this intervention.

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

Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. [2019] We evaluated the efficacy and safety of vagus nerve stimulation therapy in the treatment of 11 patients with chronic treatment-resistant depression. Mood was evaluated at frequent intervals over the year following implantation. All measures of depression, including the Hamilton Rating Scale for Depression reduced significantly. The response and remission rates were 55% and 27% respectively at 1 year. Side-effects were common, and some were severe.

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

[Vagus Nerve Stimulation (VNS) in Depression]. [2023] Major depressive disorder is a common mental health disease with a chronic and treatment-resistant course in about one-third of patients. Invasive vagus nerve stimulation (VNS) as a long-term adjunctive treatment option has increasingly been used in the last years. VNS was CE-certified in the European Union for use in chronic and treatment-resistant depression in 2001. Method In this narrative literature review we provide an overview on VNS as a treatment option in patients with depression. We particularly focus on aspects with high clinical relevance. Results Indication to conduct VNS is determined after comprehensive evaluation of the patients' symptoms and psychiatric history. After education of patients and caregivers and obtaining informed consent, a pacemaker-like pulse generator is implanted in the left chest in a short surgical procedure. In the first weeks after implantation, the stimulation is turned on stepwise in an outpatient setting. The left vagal nerve is stimulated for 30 sec. every 5 minutes. Hoarseness during stimulation is the most frequent side-effect. There is a delay in the onset of antidepressant action of about 6-12 months. In a large registry, the cumulative response rate after 5 years was significantly higher (67.6%) in patients treated with VNS plus treatment-as-usual (TAU) than TAU alone (40.9%). Long-term benefits of VNS on quality of life, cognition, morbidity and mortality have been described previously. Conclusion VNS is a long-term safe treatment option in severely affected patients with depression with positive impact on depression severity, quality of life and cognitive function. Increase of monoaminergic transmission and anti-inflammatory effects of VNS are possible mechanisms of action.

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] To determine the efficacy of vagus nerve stimulation (VNS) for treatment of depression.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation for Depression: A Systematic Review. [2020] Background: Depression is a common mental disorder worldwide. Psychological treatments and antidepressant medication are the usual treatments for depression. However, a large proportion of patients with depression do not respond to the treatments. In 2005, Vagus nerve stimulation was approved for the adjunctive long-term treatment of chronic or recurrent depression in adult patients experiencing a major depressive episode who had failed to respond to four or more adequate antidepressant treatments. However, the efficacy of VNS for treating depression remains unclear. Accordingly, we performed a systematic review to evaluate the efficacy and safety of VNS. Methods: We conducted a systematic review in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Systematic search was performed in the database of Pubmed, Embase, CENTRAL, and Web of science for identifying the suitable trials. Suicidal rate was considered as the primary outcome in this review. Result: Only two randomized sham controlled add-on studies including 255 cases (134 with VNS treatment and 121 control cases) were included in this review. None of the studies reported suicidal rate. We performed a qualitative analysis and it is suggested that there was no significant statistic difference between VNS and sham VNS on the score of 24-item Hamilton Rating Scale for Depression (HAMD24) (MD: -2.40, 95% CI: -7.90 to 3.10). Similar findings were also reported on improvement percentage of HAMD24 (MD: 1.00, 95%CI: -6.06 to 8.06), Montgomery-Asberg Depression Rating Scale (MADRS) (MD: 4.70, 95%CI: -2.98 to 12.38) and 30 item Inventory of Depressive Symptomalogy-Self-Report (IDS-SR30) (MD: 4.9, 95%CI: -1.89 to 11.69). However, a marginal difference of Beck Depression Inventory self-rating score was detected between the real and sham treatment (MD: 7.80, 95% CI: 0.34 to 15.26). Aminor effect of IDS-SR30was also found in real VNS group (RR: 2.33, 95% CI: 1.07 to 5.10). Conclusion: The efficacy and safety of VNS for depression is still unclear. Further randomized controlled trials are needed to confirm the efficacy and safety of VNS.

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

Adverse events in children receiving intermittent left vagal nerve stimulation. [2019] The purpose of this study was to determine the frequency of unexpected events during intermittent vagal nerve stimulation in 24 patients stimulated for a total of 61 patient years. The charts of 24 children undergoing periodic stimulation of the left vagal nerve on research protocols were reviewed to determine the nature and frequency of adverse events and the total length of time they were stimulated. Fifteen adverse events were discovered in 12 patients. Thirteen were likely related to the device, and four other events might have been related. Two of these resulted in voluntary termination of vagal nerve stimulation, and the rest were treatable. Vagal nerve stimulation was tolerated in this series of patients. As opposed to the more standard drug therapies, adverse events during vagal nerve stimulation do not necessitate termination of therapy, but these events frequently lead to unforeseen surgery under general anesthesia.

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

Vagus Nerve Stimulation for Major Depressive Episodes. [2015] Stimulation of the left vagus nerve is a novel antidepressive therapy that relies upon the vagal projections to the brain stem to modulate brain circuits involved in mood regulation. There is cumulative evidence from prospective and long-term studies that has demonstrated tolerability and effectiveness of vagus nerve stimulation (VNS) in major depressive episodes (MDE). VNS in MDE has the following advantages: symptomatic response (defined as at least a 50% improvement in MDE severity) occurs in at least 15-17% of patients after 10 weeks of VNS treatment and in at least 22-37% of patients after 12 months of VNS treatment, remissions are observed in at least 15-17% of patients after 12 months of treatment, there is a sustained response in 13-27% of patients during 12 months of VNS, and successful maintenance of the initial improvement is observed in a high percentage of patients (73-77% of patients who had meaningful or greater benefit after 3 months of treatment maintained at least meaningful benefit after 12 months of treatment). VNS is a well-tolerated treatment as indicated by the high continuation rates of VNS therapy in the D01 and D02 studies after 12 months of therapy (90-98%) and the low rate of adverse event-related study discontinuations through 12 months or more in these studies (3%). Adverse effects are characterized by the absence of systemic effects associated with drug therapy and are primarily limited to those related to stimulation of the vagus nerve; many of the common adverse effects only occurred when VNS was on with the ability to stop acute stimulation-related adverse effects immediately through the use of magnet deactivation of the VNS device. More importantly, there were no adverse cognitive and psychomotor effects observed with antidepressant drugs and electroconvulsive therapy, no overdose toxicity observed with antidepressant drugs, favorable findings in animal reproductive studies, and an ability to add VNS therapy to antidepressant drug therapy without producing drug-drug interactions. Finally, VNS has high treatment compliance because VNS therapy is programmed to work automatically without the need for action on the patient's part (no pills to swallow).

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] The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population.

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

[Vagus nerve stimulation and depression]. [2019] Vagus nerve stimulation (VNS) is an old, yet new, option for treatment-resistant depression. Despite several clinical trials over the last 15 years showing a consistent benefit-risk balance of the technic, VNS still struggles to find its place in our therapeutic algorithms. This is especially true in France, where only a few surgeries have been performed nationwide, all in the last year. The reasons behind this lag are manifolds; (1) psychiatrists usually do not consider surgical treatments, even when they are minimally invasive and reversible, (2) early VNS trials stumbled on methodological difficulties that are common to all invasive neurostimulation technics, and initially failed to provide strong evidence for its efficacy, and (3) VNS requires multidisciplinary teams involving psychiatrists and neurosurgeons that did not exist then. Nevertheless, studies of the past twenty years support VNS as a treatment of depression endowed with a unique efficacy profile: a long runner best at maintaining remission in hard-to-stabilize depression, even in the context of ECT withdrawal, and irrespective of whether it is unipolar or bipolar. Thus, VNS potentially addresses the unmet medical needs of some of the most severe and chronic patients with depression. This review aims at introducing VNS as a treatment option for depression, summarizing available evidence for its efficacy and tolerance, and delineating patient profiles that might benefit the most of such treatment.

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

Vagus nerve stimulation for severe depression. [2019] Treatment-resistant depression is a serious problem with significant costs in terms of health care dollars and patients' well-being. Vagus nerve stimulation (VNS) is one novel, device-based therapy that may be effective in this population. In this article, we review the evidence to date on the use of VNS in major depression and describe the process of VNS treatment initiation, device implantation, and dosage adjustment and monitoring. It is important for psychiatric nurses to understand the evidence base for and how VNS is used in treatment so they may enhance care of patients with treatment-resistant depression.