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 May 12, 2005
Implanted Electrodes Combat Depression
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By Amanda Gardner, HealthDay Reporter

TUESDAY, March 1 (HealthDay News) -- A procedure that involves drilling two holes into a person's skull and then implanting electrodes in the brain has shown promise in treating individuals who are severely depressed and resistant to other types of treatment.

Four of six patients who received this deep brain stimulation showed sustained improvement six months after the procedure took place, scientists report in the March 3 issue of Neuron.

The patients have now been followed for a year and are still in remission, added co-lead investigator Dr. Andres Lozano, a professor of neurosurgery at the University of Toronto.

Although deep brain stimulation to other parts of the brain has been used to treat epilepsy, Parkinson's and other diseases, this appears to be the first time it has been used to treat major depression, Lozano said.

About 20 percent of people with depression fail to respond to standard treatments. Some of these people will respond to combinations of medications plus electroconvulsive therapy, sometimes known as shock therapy. A remaining few, however, still do not get better.

The new therapy is far more refined than electroconvulsive therapy, Lozano said. "Electroconvulsive therapy is analogous to rebooting your computer," he explained. "This [deep brain stimulation] is very pinpointed, precise therapy, involving a very precise area of brain that plays a key role in depression."

For the past four or five years, there have been hints that this area of the brain, the subgenual cingulate region, or Cg25 region, played a role in depression. "When people are acutely sad, this area of the brain becomes active," Lozano said. "If you take antidepressants, the activity in this area goes down."

This information led to the hypothesis that diminishing activity in that area might improve depression. "It was as if the thermostat was set for 120 degrees and you want it to be 70 degrees," Lozano explained. "This area of the brain is running in overdrive, and it is causing depression and also interfering with the function of areas of the brain that are involved in cognitive function."

The new study involved six patients, median age 46, who had failed to respond to a minimum of four other treatments for depression, including medications, psychotherapy and/or electroconvulsive therapy. The participants were recruited from across Ontario and the deep brain stimulation procedures were performed at Toronto Western Hospital, which is affiliated with the University of Toronto.

The researchers first pinpointed the precise area of the brain in question using positron emission tomography (PET) scans. Then Lozano drilled two small holes into each side of the skull in a two-hour procedure that took place under local anesthesia. He inserted two thin wires with electrode contacts, then tunneled the wires (about the diameter of uncooked spaghetti) underneath the skin behind the ear down to the chest. An incision was made under the collarbone so a battery could be placed there. The electrodes were hooked up to the batteries (one on each side of the body). The batteries can be programmed remotely through the skin, and there is no restriction on activities, Lozano said. The batteries last for five years.

Stimulation, which is adjusted individually for each patient, takes place 24 hours a day. "We think it's going to require ongoing stimulation," said Lozano. When stimulation was turned off in one participant, the depression returned within two weeks.

In all, Lozano and his co-authors saw a "striking benefit" in four of the six patients. The other two were removed from the study after six months because they failed to improve. It's not clear why four patients improved, while the other two did not, although the individuals who did improve all had depression that began in their late teens and early 20s.

"It's one spot of the brain that is really acting as a terrorist and subjugating very widespread areas of the brain and interfering with their function," Lozano said. "If one can seek out this area and tell it to behave in a more normal fashion, then the rest of the brain follows." The four people also showed improvements in concentration and motivation, he said.

Lozano stressed that this research was "early, early" and that additional studies needed to be performed. "We don't know if this will be reproducible and sustained," he said. Researchers also don't know if the results can be generalized to all depression.

"It's only six people, so it's nothing to be too excited about, yet these patients really are the most refractory, and many of them had not been out of the house for several years," Lozano said. "Now they're talking about going to work, going to the gym, starting a business. It's really been a transformative experience for some of them."

More information

NAMI (www.nami.org ) has more on major depression.

SOURCES: Andres M. Lozano, M.D, Ph.D., professor, neurosurgery, University of Toronto; March 3, 2005, Neuron

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