Stanford Report Online

Stanford Report, October 11, 2000
Pacemaker for the brain may offer control for severe depression


A battery-driven pacemaker that stimulates the brain, similar to a cardiac pacemaker that stimulates the heart, is being touted as a promising new treatment for long-term depression. Stanford researchers are taking part in a nationwide clinical trial to test the safety and effectiveness of the new device.

"This is a trial for treatment-resistant depression," said Charles DeBattista, MD, assistant professor of psychiatry and behavioral sciences and director of Stanford's depression clinic.

"We're looking at patients who've been on a variety of medications before and haven't responded to those medications," said John Barry, MD, assistant professor of psychiatry and behavioral sciences and director of the neuropsychiatry and individual psychotherapy clinics.

Depression affects approximately 10 percent of American adults. One million of these 18 million patients suffer from the kind of severe depression that resists conventional treatments. Barry and DeBattista will evaluate patients at the Stanford Mood Disorders Clinic to determine their suitability for the new treatment. The Oreo cookie-sized device is implanted under the collarbone and attached to the left vagus nerve during a same-day surgery procedure, but patients remain at the hospital overnight for observation. Patients return for regular clinic visits so the researchers can monitor their response to the treatment.

The device, called the Vagal Nerve Stimulator (VNS), sends a mild electrical pulse to the vagus nerve (10th cranial nerve), which stimulates regions of the brain believed to control emotions. It was originally devised as a treatment for epilepsy, but physicians soon realized that patients receiving vagal nerve stimulation reported mood improvements.

"The vagus nerve affects an area in the brain responsible for epilepsy, and the same area is probably involved in depression as well," said Barry.

"Many medications we use to treat epilepsy, we now also use to treat depression -- Depakote for example. That observation gave us some clues that this might be a good treatment for certain kinds of mood disorders like depression. People who've had these implants tend to feel better -- their mood is better," said DeBattista.

The device, manufactured by Cyberonics Inc., Houston, Texas, was approved by the Food and Drug Administration in 1997 as a treatment for epilepsy but is still in the early stages of investigation as a treatment for depression. Currently, electroconvulsive therapy (ECT) -- which consists of an electrical shock to the brain administered under general anesthesia to induce a generalized seizure -- is one of the few treatments available for sufferers of severe depression. "This population often is given ECT, which has a high relapse rate. We hope with this device that efficacy can be maintained over time," said Barry.

He and DeBattista hope to recruit 15 to 20 patients to join the trial at Stanford. Nationwide, 200 patients are being sought. Patients in the trial will be assigned to one of two groups for the 12-week study. Half will have the device switched on immediately. During the first four weeks, the researchers will adjust the stimulation impulse, duration and frequency to find a level that is comfortable and effective for each patient, beginning with a 30-second electrical pulse, every five minutes, 24 hours per day. Stimulation continues at the optimal level for the eight-week treatment phase of the trial.

The remainder will serve as a control group, and their implants will remain inactivated for the 12-week period. At the end of the trial, all patients have the option of having the electrical stimulation switched on and can continue the treatment as long as they wish. The researchers will monitor all patients for at least two to three years.

In a preliminary test of the device involving 30 patients, 40 to 50 percent of them showed improvement in their condition as assessed using two different depression-rating scales. "This is a highly treatment-resistant population. Therefore [these results are] quite encouraging -- some patients noticed effects in the first few weeks of treatment," said DeBattista. "It really is a novel way of looking at depression."

According to the researchers, side effects experienced by patients using the device for treatment of either epilepsy or depression are infrequent and limited to pain or irritation at the site of the implant and voice alteration or hoarseness during the 30-second electrical pulse due to the vagus nerve's effect on muscles in the larynx (voice box). Patients can continue their usual medications throughout the study. Patients interested in participating in the trial should call research coordinator Emily Loraas at (650) 723-2774.