Treating depression could change significantly given the results of a small Canadian clinical trial that culminated in 2005. Pacemakerlike electrodes stimulating a deep-brain region called the subgenual cingulate freed several patients from heavy depression that had resisted medication, talk therapy and even electroconvulsive (shock) treatment. Study co-author Helen S. Mayberg, who began the work at the University of Toronto before moving to Emory University, cautions that any trial so small —just six patients —must be considered provisional. Yet four of the six subjects felt dramatic and lasting effects.

University of Toronto neurosurgeon Andres Lozano implanted battery-powered, pacemakerlike devices underneath a patient's clavicle, then ran flexible, hair-thin electrodes to the subgenual cingulate, a well-buried cortical area that Mayberg had previously found active in depressive or sad states. The electrodes delivered pulses of four volts, 130 times a second. Mayberg hypothesized that in badly depressed patients the subgenual cingulate acts like a switch left open, allowing depressive circuits to run amok.

Her results suggest that the regular stimulation might moderate that activity. The four improved patients felt the effects right on the operating table. “They would say, ‘The noise is gone,’” Mayberg recalls. “Or ‘The void has disappeared.’ This was not just mood elevation. It was relief of an agonizing state.” In 2005, after a year of living with the continuous impulses, the four patients had lowered their scores on the Hamilton Depression Rating Scale from the soul-deadening high 20s to between one and eight — quite healthy.

Mayberg is trying to organize larger trials. She is also searching for the exact curative mechanism. “We’re turning off something right in the operating room,” she says. “Now we need to find out what.”