According to the National Institute of Mental Health, more than 21 million Americans suffer from some kind of depressive disorder. For about 4 million of the most severe cases, no treatment can help. But there is a promising experimental therapy now in clinical trials that, in essence, "rewires" the brain. It is most definitely medicine on the cutting edge.
Diane Hire of Norwalk, Ohio, is 54 years old. For the past 20 years, she has lived with severe, unrelenting depression.
"You felt like a dead person walking. There was just nothing left in me," Hire told ABC News. "I had no emotion left. I had no energy left. I had nothing. I was an empty shell of a person."
She was prescribed one anti-depressant after another, as well as psychotherapy. Nothing worked. She tried to commit suicide three times.
"It was unbearable. It was just unbearable." she said. "You start to feel that your friends and family would be better off without you." Hire reasoned, "There's just not anything that's going to change. So why live like this?"
Finally, her psychiatrist suggested a radically different, experimental treatment: deep brain stimulation, the same procedure that's been used safely for two decades to calm the tremors of Parkinson's disease and is now being tested on severe depression.
Using a brain model, Dr. Ali Rezai, a neurosurgeon at the Cleveland Clinic and lead investigator of the clinical trial for this treatment, showed ABC News how deep brain stimulation works.
"We slowly advance this probe into the brain," he said, "and it goes to the precise location where there's abnormal activity going on resulting in depression. ... [Then] we activate it by inserting tiny electrical pulses."
The pulses are mild enough so that the patient does not feel anything, but they're powerful enough to change a patient's mood.
With Hire's head immobilized in a brace and electrodes deep inside her brain, doctors start adding those electrical "pulses" to her brain. Diane feels the effects immediately.
"I'm starting to smile. I'm so happy," she said.
Minutes later, doctors increase the electrical intensity, and her mood improves further. Hire smiles, saying, "I feel good." She tells the surgeons she cannot remember the last time she felt like this.
Then, when doctors add more of the mild, electrical pulses, Hire laughs. "I just feel happier."
To keep her depression-free, doctors implant two battery-powered pacemakers in her chest with wires running under her skin to that spot deep inside her brain.
Today, Diane walks 50 miles a week and is eager to be around friends and family.
"They didn't create a new person. And they're not manipulating my mind," she is quick to point out. "This is me."
This clinical trial using deep brain stimulation to treat depression began at the Cleveland Clinic in 2003. Brown University Medical Center and Massachusetts General Hospital are also now testing this approach. According to the most recent data presented at a neurological conference in Chicago last month, eight of the 17 patients treated with deep brain stimulation have seen significant improvement.
Another clinical trial using the same treatment but focusing on a different target area in the brain is being conducted at the University of Toronto and Emory University. Several more years of testing, on both approaches, are still required before doctors have enough data to submit to the Food and Drug Administration for approval.
"There is such a huge difference," said Diane. "I can jump out of bed and look forward to the day. And I never used to do that."