Vagus Nerve Stimulation Shows Promise in Treating Resistant Depression

May 09, 2001

New Orleans (MedscapeWire) May 9 — Evidence is mounting that vagus nerve stimulation (VNS), used to treat severe epileptic seizures, is effective in treating depression that has not responded to other therapies.

In the first nationwide clinical trial of its kind, presented at the annual meeting of the American Psychiatric Association in New Orleans, Louisiana, investigators from the Baylor College of Medicine in Houston, Texas, reported that nearly half of patients with treatment-resistant depression who had the VNS system implanted — dubbed by some as a pacemaker for the brain — were doing well a year later.

Of 60 patients enrolled in the study at 4 medical centers, 30% showed at least a 50% or better improvement in depression and quality of life after 10 weeks of VNS treatment. Data presented on the first 30 patients showed sustained or further improvements after a year: 46% had significantly improved or were free of depression. The patients had suffered from depression an average of 10 years; most had failed numerous treatments, from electric shock therapy to combinations of antidepressants.

"At the evaluation one year after the implant the majority of patients who had responded acutely to VNS seemed to be holding their own — even doing better," says Lauren B. Marangell, MD, lead author of the study and director of mood disorders research at Baylor. The findings took researchers by surprise. "A continuing improvement in response rates for refractory depression is highly unusual," Dr. Marangell says, suggesting that VNS may become more potent over time.

The study, which began in 1998, should offer hope to the nearly 20 million Americans 18 and older who struggle with depression in a given year. According to the National Institute of Mental Health, 2-3 of 10 people with the disorder suffer from refractory depression.

Scientists don't know exactly how VNS acts in the brain to cause an antidepressant effect. They suspect that the electrical stimulation increases the activities of some neurotransmitters, such as serotonin, while decreasing the actions of others. A generator about the size of a pacemaker is implanted in the patient's upper chest and connected via electrodes to the left vagus nerve in the neck, which communicates messages to the brain.

The device is programmed to deliver electrical current every 5 minutes, and researchers say the adverse effects of VNS are minimal. As the nerve is stimulated, some people may experience a tingling sensation, hoarseness, or the urge to cough.

In April, the VNS system, manufactured by Cyberonics, Inc., of Houston, was approved in Canada (and a few weeks before that in Europe) for treatment of resistant depression — both unipolar and bipolar. It has been approved in the United States since 1997 for epilepsy and has been used by more than 12,000 people worldwide.

Meanwhile, investigators are in the midst of the first controlled study of VNS implanted in 210 patients at 21 sites across the US and Canada. The trial began a year ago and data should be available by mid-2002. Each study participant received the device, but in half of the patients, it was turned off for 3 months to compare their responses to the VNS group. (All of the patients had been informed of the possibility that the generator could be turned off for part of the study).Citing the importance of finding a breakthrough treatment for refractory depression, the US Food and Drug Administration has agreed to an expedited review of the study. Marangell says that this is particularly exciting because with FDA approval, the coding is already in place for reimbursement by Medicare and Medicaid.

"What a lot of patients like about VNS is that it legitimizes depression as a medical condition in a way that Prozac doesn't," she says. But VNS is expensive, and insurance coverage — even for treatment of epilepsy — varies widely. The device itself costs $12,000 and a neurosurgeon who iiimplants it may charge another $10,000 to $15,000. The battery lasts 10 to 12 years.

James A. Halikas, MD, a professor of psychiatry at the University of Minnesota attending the APA meeting, suggests that people who feel they may be candidates for the device put pressure on the FDA to increase the probability of timely approval. "In my practice, I see a lot of patients for whom therapy hasn't worked. Many would line up for an implant if VNS was covered by insurance."