For many people who don’t respond to standard antidepressant treatment, electric brain stimulation — known as vagus nerve stimulation — has been shown to effectively relieve severe symptoms of depression. But how exactly does it work?
Researchers at Washington University School of Medicine in St. Louis are beginning to discover how implanting these electronic stimulators lessens depression.
Their findings, published in the journal Brain Stimulation, reveal that vagus nerve stimulation causes changes in brain metabolism weeks or even months before patients feel relief from symptoms.
“Previous studies involving large numbers of people have demonstrated that many with treatment-resistant depression improve with vagus nerve stimulation,” said first author Charles R. Conway, M.D., associate professor of psychiatry.
“But little is known about how this stimulation works to relieve depression. We focused on specific brain regions known to be connected to depression.”
The study involved 13 people with treatment-resistant depression. Their symptoms had not improved after several months of treatment with as many as five different antidepressant medications. Most had been depressed for at least two years, but some had been clinically depressed for more than 20 years.
All of the patients underwent surgery to have a device inserted that would electronically stimulate the left vagus nerve, which runs down the side of the body from the brainstem to the abdomen. Once activated, the device delivers a 30-second electronic stimulus to the vagus nerve every five minutes.
The researchers used positron emission tomography (PET) brain imaging on the patients before their first stimulation, and again three and 12 months after stimulation had begun.
Over time, nine of the 13 participants experienced improvements in depression with the treatment.
However, in most cases it took several months for improvement to occur.
In those who reported improvement, the scans showed significant changes in brain metabolism following three months of stimulation.
This typically preceded improvements in symptoms of depression by several months.
“We saw very large changes in brain metabolism occurring far in advance of any improvement in mood,” Conway says. “It’s almost as if there’s an adaptive process that occurs. First, the brain begins to function differently. Then, the patient’s mood begins to improve.”
Many of those who responded to the device eventually were able to stop taking medication, said Conway.
“Sometimes the antidepressant drugs work in concert with the stimulator, but it appears to us that when people get better, it is the vagus nerve stimulator that is doing the heavy lifting,” Conway explains. “Stimulation seems to be responsible for most of the improvement we see.”
Furthermore, the PET scans showed that structures deeper in the brain also begin to change several months after nerve stimulation begins. Many of those structures have high concentrations of brain cells that release dopamine.
There is growing evidence that problems in dopamine pathways may be especially important in treatment-resistant depression, said Conway.
The finding that vagus nerve stimulators influence those pathways may explain why the therapy can help and why, when it does work, its effects are long-lasting. Patients who respond to vagus nerve stimulation tend to get better and to stay better.
“We hypothesized that something significant had to be occurring in the brain, and our research seems to back that up,” he said.