(2024-12-17) The Vagus Nerves Mysterious Role In Mental Health Untangled

The Vagus Nerve’s Mysterious Role in Mental Health Untangled. Wellness influencers claim we can ice, tone or zap the vagus nerve to fix almost anything—long COVID, headaches, poor memory, extra pounds, the blues. Much of that hype is unfounded. Still, some research on the vagus nerve is intriguing enough—and promising enough—to draw serious scientific attention.

In 1997 the U.S. Food and Drug Administration approved a vagus nerve stimulation (VNS) device that can be surgically implanted

In 2005 the FDA certified a similar device for treatment-resistant depression.

Clinical trials are underway on so-called transcutaneous VNS (tVNS) devices,

The vagus vine’s power may be partly mythical, and the research on it is by no means conclusive or clear. But some scientists say it offers hope for millions suffering from complex, hard-to-treat conditions.

In 1988 neurologist James Kiffin Penry and neurosurgeon William Bell became the first to implant a VNS device into a human to treat epilepsy.

The treatment had a remarkable side effect: over time it made people happier. Their mood lightened even if they still had frequent seizures.

Scientists now know that the vine carries information about heart rate, digestion and, more broadly, the state of the body to many of the brain regions implicated in psychiatric illness

If cytokines circulate continuously for months or years—from stress, chronic infection or autoimmune disease—inflammation can cause insidious harm.

To test their anti-inflammatory drug, the researchers injected mice with a toxin that triggered an immune reaction. But there was a mix-up: instead of injecting the toxin into the brain, a member of the lab injected the mice in the abdomen, causing systemic inflammation.

Much to Tracey’s surprise, the anti-inflammatory drug they subsequently delivered into the brain reduced the inflammation in the body. How did that happen? The blood-brain barrier should have prevented the drug from leaving the brain.

It turned out that the vagus nerve had carried the drug’s signal from the brain deep into the body

Even more astonishing, Tracey found that stimulating the vagus with electricity alone also inhibited inflammation throughout the body—no drugs needed.

If exciting the vagus nerve could subdue inflammation without drugs and their side ­effects, it could mark a breakthrough in treating chronic conditions safely.

Almost a third of people with major depression also have inflammation. “Cytokines cause depression,”

Depression seemed like a good place to start. People with depression experience a variety of symptoms, but they share some commonalities

Efforts to use vagus nerve treatment to help people with depression took off—and then stalled. The FDA approved VNS in 2005 after several trials found that using it for a year alleviated depression in at least 30 percent of patients. Two years later, however, the Centers for Medicare and Medicaid Services (CMS) announced that it would not pay for the treatment, citing insufficient evidence of efficacy. The treatment costs about $30,000 or more in the U.S., which puts it out of reach for most patients

Following the success of (the 2017) study, the CMS agreed to reimburse patients participating in a large new clinical trial the device maker launched in 2019.

Optimistically named RECOVER, the trial could establish VNS eligibility for Medicare coverage.

had a history of attempted suicide—people who would normally be excluded from drug clinical trials. “This study is for the sickest of the sick

But in June 2024, after a year of observing about 500 patients, the RECOVER trial posted mixed results. Many of the patients with depression who were getting pulses to their vagus nerve showed meaningful improvement—but so did those whose devices were not activated. (placebo)

Meanwhile the RECOVER study continues. Conway and other researchers hope its data can be used to predict who would most likely benefit from future VNS work. The study did not track inflammation, but it could turn out to be a key marker.

meanwhile identified mechanisms by which inflammation can cause depression

All this knowledge has, however, been hard to convert into treatments

even for the third of people with depression who have proinflammatory cytokines in their blood, VNS might reduce their depression but not their inflammation. Something else is going on.

Depression is a complex and variable condition. “Depressed people may look similar, but they don’t all have the same disease,” Tracey says. This heterogeneity could mean different types of vagus nerve signals might be effective for different people

Few people with depression or other psychiatric disorders have access to VNS outside of a clinical trial (approximately 125,000 patients have received an implant). Instead an increasing number of researchers and clinicians have turned to tVNS, which is cheaper and more convenient.

Most studies with tVNS have been small and limited

Increasingly, clinicians are combining tVNS with conventional treatments such as antidepressants and cognitive-behavioral therapy. These devices also enable individuals to self-treat many different conditions, including anxiety, stress and even general malaise. There is, however, no consensus on protocol for any given condition