Vagus nerve stimulation, which has been used for nine years in the USA as a treatment for medication-resistant epilepsy is now entering American clinical practice as a promising supplementary therapy for treatment-resistant depression.

Implantation of the stimulator is an outpatient procedure that takes about 45 minutes. Two incisions are made - one in the neck beside the larynx -the other in the chest. An electrode is wrapped around the vagus nerve through the neck incision, and a pulse generator is implanted in the chest. With the wires connecting the two components tunneled under the skin, the system is entirely subcutaneous.

After the incisions have healed, the device is turned on, sending intermittent, preprogrammed, mild pulses through the vagus nerve into the brain. Although results are not immediate and many patients do not respond at all, a significant number eventually feel relief.

“This is a new treatment modality that may help about one in three people with very severe depression,” said Mark H. Rapaport, MD, Chairman of Cedars-Sinai Medical Center’s Department of Psychiatry, noting that studies are underway to determine if there are predictors that will help psychiatrists identify which patients are most likely to have a good response.

“When you consider that chronic, severe depression is associated with both increased morbidity and increased mortality, giving somebody a one in three chance of feeling a lot better is a considerable improvement, and it is a hope we can offer.”

Rapaport participated in a major clinical trial that led to approval of the device for use in the USA as a treatment for depression. In that blind study, half of the patients undergoing vagal stimulation had the device turned on two weeks after surgery. The other half had the device implanted but not turned on. At three months, there was little discernable difference between the two groups. In fact, a difference was evident only on the more sensitive of two inventories used to evaluate depression.

After the three month evaluation, the second group’s devices were turned on, with other medications and therapies continuing as usual. At one year post-surgery, members of both groups were compared with patients who had qualified to participate in the study but did not undergo the operation.

“We found that of the group that had vagus nerve stimulation (VNS) plus appropriate care, about a third had significant, sustained improvement. In contrast, the group of people with sustained improvement in the medication-alone group was about 10 percent,” said Rapaport.

“If you look at the progression of change in the VNS data, you see that individuals who are going to respond typically begin to show a response somewhere between months three and six. Some people respond early, but the vast majority of people respond between months three and six, with a few more responding at month nine. So it takes time for VNS to work, and that makes sense because it takes time for people to heal.”

Psychiatrist Robert M. Cohen, MD, PhD, also of Cedars-Sinai, emphasized that VNS is one option among many to be considered. “The benefit of vagal stimulation is that you don’t have to withdraw patients from any of their current medications, and you can still work toward increasing the effectiveness of their drug treatment. It’s like having an additional weapon, but you’re not taking away any of the other weapons. That’s what I try to emphasize about this procedure. It’s something to be added, but that doesn’t mean we stop trying in the other dimensions such as psychotherapy, changes in medication management or electroconvulsive therapy.”

Based on studies to date, 10 percent of people with treatment-resistant depression might have a marked clinical improvement without vagal stimulation over the course of two years. With nerve stimulation, 33 percent will have marked clinical improvement, meaning that perhaps only 23 percent more individuals are improving than would have improved anyway.

Vagus nerve stimulation was approved by the FDA for treatment of refractory epilepsy in 1997. Physicians noted that patients’ moods also appeared to improve, which led to clinical trials and last year’s approval for use of the technique in treatment-resistant depression.