Vagus Nerve Stimulation: Does It Work for Treatment-Resistant Depression?

Electrically stimulating one of a pair of major cranial nerves has long been thought to help produce significant relief in many people who have experienced major depressive disorder (MDD).

Vagus nerve stimulation, or VNS, is FDA-approved for patients with chronic moderate-to-severe MDD who have not responded to repeated courses of antidepressant medication. Yet the technique—which involves the implantation under the skin of a pacemaker-like device that delivers periodic bursts of electricity to the left vagus nerve—has been considered too expensive to warrant widespread clinical use in the absence of more definitive proof that the procedure provides significant, long-term benefits.

Now, that proof has been provided in a five-year-long study published in the July 2017 issue of the American Journal of Psychiatry.

“The research suggests that compared to medications alone, a combination of VNS and medications contributed to a 25 percent or greater reduction in participants with treatment-resistant MDD, but that it works slowly,” says Alik S. Widge, MD, PhD, Director of Research for the Division of Neurotherapeutics at MGH. “After five years, almost 50 percent of participants who got to remission with VNS were still in remission. That is an impressive long-term benefit. Since the cost of one emergency room visit and a few days of hospitalization for someone with MDD equals the cost of the VNS surgery, the procedure appears to pay for itself.”


You can find out more information about VNS by contacting:

MGH Division of Neurotherapeutics
149 13th Street, 2nd Floor
Charlestown, MA 02129
Phone: 617-643-4965

Clearing Hurdles

The new findings are expected to help eliminate several major roadblocks that have stood in the way of clinical availability of VNS for people with MDD. Virtually all people with MDD would likely be eligible for VNS, with the exception of people who have a history of psychosis or certain types of bipolar disorder. Yet these treatments have been difficult to access because of impediments that include:

Lack of parity between treatments for physical disorders and those for mental disorders. VNS is more likely to be considered for disorders such as epilepsy or cluster headaches than for mental disorders such as MDD, substance abuse, or post-traumatic stress disorder, even though it is also effective against those conditions.

Lack of insurance coverage. Data have been lacking to prove that over time VNS for depression results in fewer expensive episodes of emergency room treatment and hospitalizations among patients with MDD, thus suggesting that it is cost-effective. The new research may help medical professionals win the argument for VNS insurance coverage for their patients.

Insufficient levels of interest to date in research into VNS for MDD.

Lack of knowledge/support for VNS in the treatment community.

“This new study shows that you can increase the chances that a patient will avoid another episode of depression,” Dr. Widge says. “It shows that VNS can make people better. Yes, it’s expensive, but in the long run, it’s cost-effective. This information should go a long way toward convincing insurance companies to cover the procedure.”

Targeting the Vagus Nerve

The left vagus nerve is part of the gut-brain connection that links the brain with major body organs.

“It’s easy for surgeons to access since it passes through the neck directly under the skin,” says Dr. Widge. “It is wired directly to the brain and to brain regions that control chemicals associated with mood, such as the neurotransmitters serotonin, norepinephrine, and dopamine, which are all involved in depression treatment.

“Stimulating the vagus nerve sends signals the opposite way than they might normally flow, sort of like kids in a playground who run up the slide and climb down the ladder. This reversal allows signals to get into the brain and change neurotransmitter levels in the outer part of the brain called the cerebral cortex, opening up a new sort of plasticity in the cortex that allows it to modify its functioning.”

Antidepressant medications are also capable of increasing brain plasticity. But the changes associated with VNS are different in ways that appear to boost the response rate among hard-to-treat patients who have failed to benefit from drug treatments, Dr. Widge says.

Side Effects

Potential candidates for the VNS procedure are evaluated on a case-by-case basis. Following surgical implantation, VNS patients usually need frequent med­ical assessments and adjustment over a period of up to three months, after which they might require only occasional visits to a medical professional.

Side effects of the procedure are generally mild and tend to fade after the first year or so. They include a change in voice quality, neck pain, difficulty swallowing, cough, breathing problems during exercise, and a sense of tightness in the throat during the five to 30 seconds of electrical stimulation.

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