But as correspondent Lesley Stahl reports, early results from an experiment in Canada have raised hopes for an answer to their suffering. It involves surgery on a region of our brains called Area 25. And, for the small group of patients who have signed up, the risks seem worth taking, because this is their last resort.
"It's kind of, for me, just a feeling of sadness, hopelessness, overwhelming," says 49-year-old Debra Prupas of Toronto. She was diagnosed with depression 15 years ago. It would seem that Debra had little to be depressed about, with a career as a high-level lawyer, a new husband, Bern Grush, and two daughters adopted from China.
"I call myself the great imposter," Prupas says. "I could fake my way through it. People - nobody knew. And then in the past few years, I've not been able to do that. I can't even get out of bed."
Debra has tried everything: numerous psychiatrists, anti-depressants: more than 30 different kinds, and a dozen electric shock treatments. Nothing worked.
Spending up to 18 hours a day in bed, Debra had to abandon her job, stop seeing friends and had thoughts of suicide. That left Bern taking care of her and the children.
"I'm just absent. I don't want to go out with my husband. I don't want to talk to – I withdraw," she says. She even withdraws from her daughters.
Coincidentally, at nearby Toronto Western Hospital, researchers had started a pilot study on a new treatment for people like Debra.
Studying the brain scans of severely-depressed patients, Dr. Helen Mayberg, the study's lead neurologist, kept seeing that a small almond-shaped node was in over-drive.
"The area of the brain that was the most active was Area 25," Dr. Mayberg explains.
Area 25 – deep in the very center of our brains – is connected to other areas that control sleep, appetite and drive, all the things that go haywire when someone's depressed. Mayberg's theory is if you cool off area 25, you treat the disease.
She decided to try a technique called deep brain stimulation, that involves threading two thin electrodes through the brain, directly into Area 25 and stimulating it with continuous pulses of electricity from a pacemaker in order to jolt it back to normal.
Mayberg's research partner, neurosurgeon Andreas Lozano, says it's a far more targeted treatment than anti-depressants.
"The difference is, with antidepressants, that the 100 billion neurons in your brain get the drug. And here we estimate that we're affecting only a few hundred thousand neurons. And so, this is a surgical strike," he explains.
And like any brain surgery, there are risks, like stroke or infection.