Depression affects more than 300 million of us, and sometimes, treatment works.
It may take a few attempts to find the right medication or therapy, but once you do, symptoms ease, and life becomes more manageable.
But for up to a third of people with depression, no standard treatment helps.
The problem isn't just that depression is hard to treat, but also that even when a treatment does work, it sometimes stops working.
Now, hopeful results from a major clinical trial suggest a small implanted device could provide lasting benefit for some people with severe treatment-resistant depression.
We're seeing people getting better and staying better," says psychiatry researcher Charles Conway from Washington University in St. Louis.
The treatment is called vagus nerve stimulation (VNS).
In a paper published in the International Journal of Neuropsychopharmacology, Conway and his colleagues say VNS produced long-lasting improvements in some people who had lived with severe depression for years.
In many cases, that was decades.
The vagus nerve is one of the longest nerves in your body, running from the brainstem through the neck and chest all the way down to the abdomen, connecting your brain to the heart, lungs, and digestive system.
VNS therapy involves surgically implanting a small device – similar in size to a pacemaker – under the skin of the chest.
A thin wire connects it to the left vagus nerve in the neck, and the device delivers brief, low-level electrical pulses at regular intervals.
The research comes from the RECOVER trial, which enrolled 493 people in the US. All of them had at least four failed treatment attempts to treat their current episode of depression, but many had tried far more.
"On average, each patient had already tried 13 treatments that failed to help them before they enrolled in the trial," Conway said in 2024.
"They had spent more than half of their lives sick with depression."
The participants had VNS devices implanted, but for the first 12 months, only half of the devices were switched on; the other half of the participants served as the control group.
Last year, the team reported in two studies that participants who received the VNS treatment showed promising improvements in their depressive symptoms.
The 2026 report focuses on the outcomes in the 214 patients who had active VNS from the beginning of the trial. The researchers wanted to know whether the improvements some patients experienced held up through the second year.
The answer, for most of them, was positive.
"With this kind of chronic, disabling illness, even a partial response to treatment is life-altering," Conway says.
"And with vagus nerve stimulation we're seeing that benefit is lasting."
About 69 percent had a meaningful improvement on at least one measure after 12 months. And among those people, more than 80 percent maintained or improved their benefits at 24 months across measures of depressive symptoms, quality of life, and daily functioning.
For those who had experienced the strongest response at 12 months – defined as a 50 percent or greater reduction in symptoms – 92 percent were typically still showing benefit two years in.
"We were shocked that one in five patients was effectively without depressive symptoms at the end of two years," says Conway.
"These results are highly atypical, as most studies of markedly treatment-resistant depression have very poor sustainability of benefit, certainly not at two years."
On average, the patients in this trial had lived with depression for 29 years. Three-quarters were unable to work.
"We believe the sample in this trial represents the sickest treatment-resistant depressed patient sample ever studied in a clinical trial," says Conway.
One of the most exciting findings involved the people who had not benefited from VNS in the first year.
Roughly one-third of those who showed no meaningful benefit at 12 months went on to improve by 24 months. That suggests VNS may take a while to show benefits in some people, but it can help eventually.
It's worth noting the trial was funded by LivaNova, the company that manufactures the VNS device, which has a financial interest in the trial's outcome.
The data are intended to inform a coverage decision by the US Centers for Medicare and Medicaid Services, which currently does not cover the therapy.
The US FDA approved VNS for treatment-resistant depression in 2005, though exactly how it works on depression isn't fully understood.
For now, the results suggest VNS is not a rapid fix and not everyone responds.
Related: Some Signs of Depression May Show Up in Blood, Study Finds
That slow onset of antidepressant effects means getting these longer-term results is especially important.
"Seeing results like that for this complicated illness makes me optimistic about the future of this treatment," says Conway.
The study has been published in the International Journal of Neuropsychopharmacology.
This article was fact-checked by Michael Irving and edited by Peter Dockrill. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.