In a small but potentially landmark study, four out of six formerly treatment-resistant patients got better after electrodes were implanted in a region of their brains thought to drive depression.
Electrical stimulation of the brain using a pacemaker-like device was introduced several years ago to help control seizures in patients with epilepsy and help Parkinson's disease patients better control their movements.
But this is the first time so-called deep-brain stimulation has been used to treat major depression.
Living a Nightmare
Debbie (not her real name) is typical of the patients in the study. She tells WebMD that her third bout of depression had lasted eight years when she decided to have the experimental surgery a year and a half ago.
Her dark moods left her suicidal and unable to function. While antidepressant drugs work for most people with depression, they did nothing to lift Debbie's depression. She says the only thing electroconvulsive "shock" therapy did was wipe out a big part of her memory.
"I was to the point where I wasn't really planning on living this nightmare too much longer," the 47-year-old Canadian says. "I had been hospitalized repeatedly because I was a danger to myself. I would have tried anything."
Deep brain stimulation targeted an area of Debbie's brain known as the subgenual cingulated region, or Cg25. In earlier research, Helen Mayberg, MD, showed that Cg25 is overactive in people with treatment-resistant depression.
In collaboration with Andres Lozano, MD, who is a leading expert on deep-brain stimulation, Mayberg and colleagues theorized that sustained electrical jolts could normalize the targeted region and make the entire brain behave more normally.
How It's Done
Two holes, the size of nickels, were drilled into the skulls of the patients who remained awake. The area of the surgery was numbed with anesthetic. Using magnetic imaging to guide them, surgeons then implanted two thin wires with electrode contacts near the Cg25 area of the patients' brains. The loose end of the wires were then threaded under the skin and attached to the pacemaker device, which was implanted in the chest.
All six of the patients reported improvement soon after the surgery. Two of the six became depressed again within six months.
The four other patients had few depression symptoms six months after surgery, and all still have the implants. Imaging studies revealed brain changes consistent with a return to normal Cg25 activity. These changes have also been seen in depressed patients who respond well to drug treatment.
The findings are reported in the March 3 issue of the journal Neuron.
Mayberg says the findings could represent the first step in a paradigm shift in the thinking about depression. Drug treatments target chemical imbalances within the brain. But the early research indicates that for some patients successful treatment will require "rewiring" parts of the brain's circuitry.
"This study tells us that this strategy has real potential … that our first target [within the brain] looks like it was a good selection," she says. "It may be that there are other areas of the brain that are better, but that remains to be determined."
Return to Normal
One of the big advantages of the brain pacemaker is that the electrical impulses can be adjusted in patients who don't respond as hoped. Debbie says it took about a year of tweaking, but she now feels "perfectly normal" for the first time in almost a decade.
Unable to do much more than stare out her bedroom window for hours at a time before the surgery, she is now planning to open her own business.
"Unlike the drugs that have failed me, I feel like if, God forbid, this stops working they can make adjustments to get me back on the right track," she says.
All agree that more study is needed to confirm the findings, and that, as with Parkinson's disease, only the sickest patients who don't respond to other treatments would be candidates for the procedure.
"Even brain surgery that is relatively benign, as this is, is a serious procedure," Mayberg says.
"You don't operate on someone's brain if there are other reasonable treatment options. But this is also a serious disease that leaves people morbidly sick for long periods of time. When you see these people living normal lives the way other people do, it is both sobering and humbling," she explains.