E.B. Writers of Dallas

By Esther M. Bauer
Special to The Washington Post
Tuesday, March 28, 2000

Every few minutes a generator that has been implanted in Claude Jones's chest emits a signal that researchers hope will make him feel better.
The device, about the size of a pocket watch, sends an electrical impulse to stimulate the vagus nerve in his neck. That nerve tweaks the limbic system, which is the mood and emotional center of the brain. The gentle current lasts a few seconds and is sent every five minutes, 24 hours a day.
Jones hopes the device will eventually help him enjoy being alive. He has not had that feeling in more than two years.
Researchers are testing vagus nerve stimulation on Jones and several other patients whose depression has not responded to other treatments. It's estimated that 1 million people in the United States suffer from intractable depression; 15 percent of them will eventually commit suicide.
Jones's depression has persisted despite treatment with many kinds of medication, counseling and electroshock therapy. For the past two years he has had weekly sessions with a psychiatrist and has been hospitalized four times, once after a suicide attempt. He now takes eight pills a day: six for depression and two to help him sleep. A series of 10 weekly electroshock treatments only made him forgetful--which has kept him from getting back to his job as a lineman
for a utility company.
"Not being able to concentrate isn't too good when you work with live electricity all day," says Jones, 49, whose hands tremble uncontrollably as a side effect of his medications. He has been receiving disability payments for the last six months and lives in his parents' summer cottage 70 miles southeast of Dallas. He mostly sits on the porch, his mother reports.
Although the nerve stimulation treatment is fairly exotic, the implantation is uncomplicated, a 90-minute surgery. Earlier this year, a neurosurgeon at Zale Lipshy University Hospital in Dallas implanted the pacemaker-like device midway between Jones's collarbone and his nipple, then tunneled under his skin to attach the generator via small wires to electrodes the surgeon had wrapped around his vagus nerve. When stimulated by the electrical impulses, the nerve alters functioning
of the components of the limbic system that affect mood.
By the second week after the surgery, Jones began experiencing what his doctors had warned would be a "feeling of fullness" in his throat when the electrical impulse came. Jones says, "Every time I feel that thing go off, it gives me hope."
Actually, Jones is feeling the side effects of the stimulation, not the electrical impulse itself, which is undetectable. If he tries to speak while the impulse is being administered, he is momentarily hoarse. In addition to stimulating the vagus nerve, the impulse momentarily alters the opening of his larynx and consequently the pitch of his voice.
The research is based at the University of Texas Southwestern Medical Center in Dallas, which with three other medical centers completed a pilot study of vagus nerve stimulation that was published in the February issue of the journal Biological Psychiatry.
In that study 30 patients were scored before and after
the implant on a roster of depression symptoms that they were feeling: sadness, low energy, sleeplessness, feelings of guilt, lack of appetite, inability to concentrate or make decisions, suicidal thoughts and feelings of worthlessness, helplessness and hopelessness. Twelve of the 30 patients receiving implants saw their scores decline by at least 50 percent, says A. John Rush, a psychiatrist at Southwestern Medical Center.
A six-month follow-up shows continuing improvement. Now 17 patients show a halving of symptoms. "People with depression of this magnitude are in an extremely disabled state . . . barely functioning," says Rush.
A comparative clinical trial scheduled for later this year is to consist of a randomized, double-blind study of about 200 patients at 15 hospitals.
Mark George, professor of psychology, radiology and neurology at the Medical University of South Carolina in Charleston, has high hopes. "The fact that we're seeing sustained improvement among people this ill shows something important is going on," he says.
Which is not to say that anybody yet understands precisely what is going on.
The mood-enhancing effect of vagus nerve stimulation was discovered accidentally after the U.S. Food and Drug Administration (FDA) approved it in 1997 for treatment of epilepsy. Patients began noticing that in addition to decreasing their seizures it also seemed to zap them into a good mood.
"We stumbled onto this and it has the chance of saving lots of lives . . . and to help us to fundamentally understand what's going on in the brain with depression," says George.
Should the surgery win FDA approval for treatment of severe depression, surgical and long-term follow-up care would cost about $15,000, according to Houston-based Cyberonics Inc., manufacturer of the stimulation device.
Not all patients improve. The device was removed from one patient because it over energized him, making him manic and irritable. After the implant was withdrawn, his depression came roaring back, says George.
Of the study's other 12 patients who have not felt a large reduction in their symptoms, several have improved somewhat and continue to receive the treatments while those who have noticed no change are keeping the device implanted in the event that further study suggests that a different dosing schedule might help them. (The impulse can be adjusted by the researchers using a remote control linked to the generator.)
This research opens new possibilities, says George, and not just for those fitted with the implants. "If we can understand the road maps of the brain as the result of this work," he says, "we can find a way to fix it without a little tickle 24 hours a day. This technology may be a bridge to a cure that can eventually be done without surgery."
Within weeks after his implant surgery, Claude Jones's hands stopped shaking, and he improved so much that he went back to work. "I don't feel exactly happy all the time, but I don't feel down either; I guess you could say I feel normal, and for me that's something new," Jones said. © 2000 The Washington Post Company