People living with treatment-resistant depression — a disease that antidepressants can’t tackle and that can keep a person from working, socializing and engaging in their daily lives — may find relief through vagus nerve stimulation, a nationwide study spearheaded by Washington University researchers has found.

The vagus nerve connects internal organs to the brain, and specifically, it connects to the part of the brain that controls mood. Vagus nerve stimulation devices have been around for two decades, and have been approved by the Federal Drug Administration for treatment of epilepsy for nearly as long. But their use to treat mood disorders, like depression, hadn’t been so deeply studied, until now.

“It’s an extremely complex disease,” said Dr. Charles Conway, a professor of psychiatry at WashU Medicine and the principal investigator. “It’s difficult to get patients feeling better, and then keep them better.”

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An estimated 21 million adults in the U.S. live with depression, and over half experience treatment-resistant depression (TRD). TRD is diagnosed when a person is unresponsive to antidepressants, after they’ve tried at least two different types in the appropriate dosage and duration, according to the National Institutes of Mental Health.

While vagus nerve stimulation is not a new treatment option for TRD, it has not had enough large, long-term studies like this one to convince insurance companies that this treatment is worth covering, experts say.

“Getting people back to their lives is incredibly important,” said Dr. Noah Philip, a professor of psychiatry and human behavior at Brown University in Rhode Island. “I hope the people making decisions around these sorts of things can appreciate the real-world benefit that was observed here.”

Depression being resistant to treatment is somewhat unique to the field of psychiatry and treating mental health disorders, Philip said.

“In other areas of medicine, take cardiology for example, the more sick you get, the more options you have,” Philip said. “In psychiatry, once someone is past taking medication and things not working, our options for people are not great.”

This is where vagus nerve stimulation devices, originally tested to treat severe epilepsy, may stand out for patients with TRD. They’ve been used for depression before, but their effectiveness hasn’t been so broadly studied before this WashU-led inquiry.

Nearly 500 patients from across the US were involved in this study. Conway said this group of TRD patients is “potentially the most severe ever studied,” with an average of 29 years spent in depression. And on average, each patient in this study had already tried 13 antidepressant treatments, none of which successfully helped them manage their TRD, he said.

“It’s a profoundly depressed group – the sickest of the sick,” Conway said.

‘Potentially life-altering’

Each participant had a vagus nerve stimulation device surgically implanted in their chests, connected by a wire to their left vagus nerve in the back of their necks, Conway said.

“The procedure is very safe, it’s an outpatient procedure that usually takes around two hours, it’s very well tolerated in most patients, and only usually takes people around two weeks to recover from,” Dr. Conway said.

These devices are produced by LivaNova USA Inc., who co-sponsored this trial. The company did not respond to requests for comment.

For the first 12 months of the trial, only half of these devices were turned on — creating a “test” group, which would experience vagus nerve stimulation for 30 seconds every five minutes. The other half were the “sham” group, who had the devices implanted but inactivated for the first year of the trial.

Both groups were tracked in the double-blind experiment — the patients didn’t know if they were in the “test” or “sham” group, and the psychologists and psychiatrists evaluating their symptoms over the course of the study also didn’t know which group each patient fell into.

After a year, the differences in quality of life between the two groups were striking, researchers said. Conway said looking at patients in the “test” group’s self-evaluated quality of life over the first year showed serious potential to treat TRD.

“When you look at the numbers, 52% of patients experienced an improvement to their quality of life. That’s pretty potentially life-altering, and indicates to us that this treatment is working,” he said.

The WashU-led study could help convince the Centers for Medicare and Medicaid Services to add vagus nerve stimulation as a TRD treatment method — and if CMS does that, private insurance companies are more likely to follow suit, Conway said. CMS co-sponsored this study, and did not respond to requests for comment.

For Nick Fournie, who dealt with TRD for nearly a decade before his first vagus nerve stimulation device was implanted 15 years ago, the treatment was more than life-altering — it was miraculous.

“It was the start of a new life for both of us,” said Mary Fournie, his wife.

Nick said when he first sought help to manage his depression, medications didn’t do the trick.

“He had had terrible drug reactions, and some of the things he endured were very difficult,” Mary said.

Once the device was implanted, however, Nick said he felt a “dramatic” change. Mary said she did, too.

“He had the surgery and immediately there was a difference in him. Finally, it was the first time he was joyful and engaged,” she said.

Post-Dispatch photographers capture hundreds of images each week; here’s a glimpse at the week of May 4, 2025. Video edited by Jenna Jones.


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