Scientists test brain pacemakers for depression

By LAURAN NEERGAARD
27 may 2008--It's a new frontier for psychiatric illness: Brain pacemakers that promise to act as antidepressants by changing how patients' nerve circuitry fires.
Scientists already know the power of these devices to block the tremors of Parkinson's disease and related illnesses; more than 40,000 such patients worldwide have the implants.
But psychiatric illnesses are much more complex and the new experiments with so-called deep brain stimulation, or DBS, are in their infancy. Only a few dozen patients with severe depression or obsessive-compulsive disorder so far have been treated in closely monitored studies.
Still, the early results are promising. Dramatic video shows one patient visibly brightening as doctors turn on her brain pacemaker and she says in surprise: "I'm starting to smile." And new reports this month show that some worst-case patients — whose depression wasn't relieved by medication, psychotherapy, even controversial shock treatment — are finding lasting relief.
Six of 17 severely depressed patients were in remission a year after undergoing DBS and four more markedly improved, and more than half of 26 obsessive-compulsive patients showed substantial improvement over three years, say studies from a team at the Cleveland Clinic, Brown University, and Belgium's University of Leuven.
"Not all patients get better, but when patients respond, it's significant," says Dr. Helen Mayberg of Emory University, who has implanted about 50 depression patients. Her first remains in remission after five years; she estimates that four of every six show enough improvement to be classified "responders."
"We're rewiring the brain in many ways," says Dr. Ali Rezai, chief of the Cleveland Clinic's Center for Neurologic Restoration.
There's a need for innovative therapies. Up to 20 percent of depression patients and 10 percent of those with obsessive-compulsive disorder are treatment-resistent — several million people in the U.S. alone.
The rationale behind DBS is credible, says Dr. Wayne Goodman of the National Institute for Mental Health: Surgery sometimes helps worst-case patients by destroying misfiring patches of brain tissue. The electrodes are placed into similar spots, but don't destroy tissue — the electrical signals can be adjusted and turned off.
But it's not yet ready for prime-time, Goodman cautions. He worries that because the electrodes already are widely available, centers without proper training will start offering the $40,000 implant surgeries to psychiatric patients before science proves if they're really valuable.
"It is an invasive, experimental procedure," he warns, with risks including bleeding in the brain and infections. He calls DBS "the last resort for stringently selected patients."
Earlier this month, federal health officials and the Cleveland Clinic brought together the field's leading researchers to highlight progress so far and debate if it's time for much larger studies — even whether DBS might be tweaked to help people with traumatic brain injuries, such as Iraq war veterans.
"There's not enough awareness of what the potential is of this kind of stimulation," says meeting co-chair Dr. Margaret Giannini, who heads the government's Office on Disability.
In deep brain stimulation for Parkinson's, a wire is implanted within a walnut-sized area known as the thalamus, a hub of sensory information. That electrode is connected by a cable running through the neck to a pulse generated under the collarbone. Tiny electrical zaps disable overactive nerve cells, blocking tremors.
Scientists don't have nearly as much understanding of what goes awry to cause depression or other psychiatric illnesses — but they do know the thalamus isn't the right spot for those patients. They're focusing instead on two regions with names only a neurologist could love — the ventral capsule/ventral striatum and so-called Brodmann Area 25. Ignore the names; the point is that these are regions where brain circuitry involved in mood and anxiety intersect.
It's not yet clear who should have DBS in which spot, or if there are still other target areas. Much of the research to date has been funded by electrode manufacturers, with some paid for by the government — and consists of measuring patients' disability before and after DBS, not more rigorous studies that randomly assign patients to treatment.
Still, Diane Hire of Cleveland, the patient whose first smile was recorded, illustrates the hope.
The 12-year Navy veteran was medically discharged for depression and spent a decade on disability, unable to function. "I basically felt like a dead person walking. I had no feelings, no emotions," she told the scientists' meeting.
Her DBS was switched on in January 2007, and "my whole world changed," says Hire, 54. She's not back to work yet: "It is a real challenge to learn how to live as a healthy person again," she adds, saying she doesn't handle stress or multitasking well. But, "I wake up every day looking forward to what's ahead."