ILLUSTRATION: Matt Mahurin

Imagine a crushing sadness so severe it keeps you from eating, sleeping, or socializing. Though you can't sleep, you lack the energy and the will to get out of bed. Everyday decisions, like which clothes to wear, leave you paralyzed. You've no desire to do the things you once thought were fun; in fact, you can't bring yourself to do much of anything. Now, add to all that the realization that you've tried everything known to medicine, it hasn't worked, and there's a good chance you won't feel any different. Ever.

"I had nothing to lose," says Karmen McGuffee, who suffered from severe depression for a decade and was hospitalized five times for it. So she had surgeons cut open her neck, gently wrap an electrode around one of the nerves there, and plug the electrode into a pulse generator, which they slipped under the skin of her chest. About every 5 minutes, the pocket-watch-size device sends a buzz of current through the nerve and into her brain.

Six months after doctors switched on the pulse generator, called a vagus nerve stimulator, McGuffee's world looked totally different. "I had no idea that life didn't have to have a dark veil over it all the time," she says. Once unable to concentrate enough to read a newspaper, McGuffee is now an executive secretary.

Depression is distressingly common, affecting more than 120 million people around the world and sucking tens of billions of dollars out of the global economy through the cost of care and lost productivity. It's also deadly. Every year 850 000 people worldwide take their own lives, and 9 out of 10 of them are suffering from depression, another mental illness, or substance abuse. Statistics show that of those who had had treatment for depression just through visits to a doctor's office, 2 percent ultimately committed suicide, as did 4 percent of those who had to be hospitalized for depression.

Twenty-five percent of people with depression have no access to any form of mental health care; of those who do have access to care, only a quarter seek treatment. Of those who consult doctors, some 80 percent find relief in the form of drugs or some kind of talk therapy, such as cognitive therapy. But for the rest—people like McGuffee, prone to the most severe and chronic forms of depression, about 11 million of them in the developed world alone—drugs don't work.

For decades, the only other option for these people was electroconvulsive therapy, which because of the frightening side effect of amnesia is often rejected by patients. But this grim outlook is at last beginning to change. McGuffee was one of the first to benefit from a new crop of electromagnetic brain stimulation technologies that psychiatrists are testing, with the hope of curing—or at least helping—patients for whom little else works. By electrically manipulating specific portions of the brain with implanted electrodes, electric current, or magnetic fields, doctors aim to succeed where drugs fail, by producing long-lasting changes in the brain—and to do it without electroshock's significant side effects.

For a variety of reasons, including the large number of potential patients and the accumulated knowledge of how the disease works, depression is the primary target of most of these technologies. But some of these methods are already showing great promise for treating such other mental maladies as bipolar disorder, obsessive-compulsive disorder, and bulimia.

The technology McGuffee uses, vagus nerve stimulation, was the first to enter routine clinical use. A pacemakerlike device about the size of a pocket watch, implanted under the skin of the chest, pulses a nerve in the neck [see illustration, "Vagus Nerve Stimulation"]. In about 16 percent of patients like McGuffee, according to clinical studies, that electric pulsing completely quashes the symptoms of depression. It was approved as a depression therapy, for use in conjunction with drugs, by government regulators in the European Union and Canada in 2001. Last June, it became the first psychiatric device to be reviewed and approved in the United States, which has more stringent requirements for medical devices. Nevertheless, a number of psychiatrists remain unconvinced that the therapy works in enough people to outweigh the risk and cost of surgery.

Vagus nerve stimulation isn't the only technology being touted for treatment of the severely depressed. Another technique, repetitive transcranial magnetic stimulation, uses powerful magnets to generate current in well-defined portions of the brain [see illustration, "Repetitive Transcranial Magnetic Stimulation"]. Many research groups around the world have experimented with the technology. At last count the results of more than 60 depression trials performed in Australia, Israel, Taiwan, the United States, Europe, and elsewhere had been published. But clinical use is just beginning. The technology is winding its way toward a review by U.S. regulators, and the company behind it, Neuronetics Inc., in Malvern, Pa., says it could be approved within the year.

And these two are just the ones closest to the clinic. Researchers are exploring three other, more experimental technologies. One uses direct current to produce a change in the brain similar to that of magnetic stimulation. Another uses transcranial magnetic stimulators to spark seizures just as electroconvulsive therapy does but, it is hoped, without the amnesia that can accompany it. The third experimental technology borrows a device used to control the tremors of Parkinson's disease. Surgeons have begun implanting electrodes in patients' brains to switch off malfunctioning brain circuits involved in depression and obsessive-compulsive disorder.

The coming clutch of medical devices, if proven to work, could represent not just hope for the hopeless but a profound change in psychiatry. "I think it's not too big a jump to say we haven't had a new [nondrug] treatment for 40 years," says Paul Fitzgerald, an associate professor of psychiatry at Monash University, and deputy director of the Alfred Psychiatry Research Center, both in Melbourne, Australia. Fitzgerald, who does transcranial magnetic stimulation research, notes that even the drug therapies are largely derivative of each other. "Now we're really faced with the potential for a significant expansion of treatments, as long as they are introduced carefully," he adds. Noting psychiatry's often disastrous history of nondrug treatments, such as the embrace of prefrontal lobotomy in the mid-20th century, he thinks the field is approaching a watershed, for the better. "We're getting it right this time."