To assess how well the treatment worked in the longer term, researchers turned the stimulator on and off for periods of several weeks, tracking symptoms with standard questionnaires. They found that the two patients improved when the stimulator was turned on and worsened when it was turned off. In fact, Schlaepfer says, recurring symptoms were so severe that the researchers shortened one of the "off" periods for ethical reasons.

In a second study, of 11 patients, presented last week at the American Association of Neurological Surgeons meeting in Washington, D.C., scientists from the Cleveland Clinic and Brown University found that after a year of treatment with deep brain stimulation, about half the patients showed noticeable improvement, and about a third improved so significantly that they no longer met the diagnostic criteria for depression. "It's very encouraging, especially given how chronically ill and highly resistant [to medication] the patients were," says Ben Greenberg, a psychiatrist at Brown Medical School and Butler Hospital, in Rhode Island, who was involved in the study.

Still, experts urge caution in interpreting the results. For one thing, says Karl Deisseroth, a psychiatrist at Stanford who studies experimental treatments for depression, "no placebo-controlled trials have been done" to confirm how well the therapy works on a larger population.

Indeed, larger studies are on their way. A multicenter study will begin this summer at various facilities in the United States, sponsored by Medtronic Neurological, a medical-device company that makes systems for deep brain stimulation. Another trial targeting a different part of the brain is also in the works, sponsored by Advanced Neuromodulation Systems, also a medical-device company.

It's not yet clear how deep brain stimulation improves symptoms of depression. "We believe it has a more direct effect on the brain, as compared to drugs," says Schlaepfer. Different studies in humans have targeted different parts of the brain, all of which have been implicated in depression in different ways. Scientists say that more research is needed to figure out the role of each region, as well as the biological changes that underlie the antidepressant effects.