Electrical deep brain stimulation can dramatically alleviate depression that is resistant to other treatments, researchers have found in an initial study on six patients. The finding is important, they said, because up to 20 percent of patients with depression fail to respond to standard treatments--requiring combinations of antidepressant drugs, psychotherapy, and electroconvulsive treatment (ECT) that still may fail. The number of resistant depression patients can be large, since depression is the leading source of disability in adults under age 50 in North America.

The 6 month study led by Helen Mayberg of Emory University School of Medicine and colleagues showed that the patients reported immediate improvements in mood when the electrical stimulation of a few volts was applied to the implanted electrodes. These effects persisted in four of the patients for the full 6 months, with three patients achieving remission or near remission of the depression. No psychological side effects were reported, and other adverse effects were limited to minor infections around the implant site, which were treatable with antibiotics, wrote the researchers.

The researchers concluded that, although the study was limited in scope and length, deep brain stimulation "may represent an effective, novel intervention for severely disabled patients with treatment-resistant depression."

The six patients who participated in the study showed severe depression according to the Hamilton Depression Rating Scale. They had all failed to respond to at least four different treatments, including drugs, psychotherapy, and ECT.

The researchers implanted the array of electrodes in a region called the "subgenual cingulate region," which their earlier studies had indicated to be overactive in treatment-resistant depression.

Precisely calibrated stimulation of a few volts produced immediate effects, the researchers wrote. "All patients spontaneously reported acute effects including 'sudden calmness or lightness,' 'disappearance of the void,' sense of heightened awareness, increased interest, 'connectedness,' and sudden brightening of the room, including a description of the sharpening of visual details and intensification of colors in response to electrical stimulation," wrote the researchers. These effects were reversed when stimulation was turned off and returned when it was resumed.

"Unexpectedly, with application of stimulation for progressively longer periods (from 1 to 3 hr), there was an increasing and correspondingly longer carry-over of the beneficial behavioral effects beyond cessation of the stimulation," reported the researchers.

During the initial weeks of stimulation, "Patients and their families described renewed interest and pleasure in social and family activities, decreased apathy and anhedonia, as well as an improved ability to plan, initiate, and complete tasks that were reported as impossible to attempt prior to surgery."

Analysis of brain activity using positron emission tomography revealed that the deep brain stimulation corrected abnormal hyperactivity in the subgenual cingulate region, which was correlated with abnormally decreased activity in the prefrontal cortex of the brain.

Psychological testing showed that the surgery did not reduce cognitive function in the patients. In fact, patients showed significant improvement in hand-eye coordination, verbal fluency, and judgment of risk.

Over a 6 month period of chronic stimulation, four of the patients continued to show significant antidepressant response, with three showing remission or near remission of illness, reported the researchers.

Helen S. Mayberg, Andres M. Lozano, Valerie Voon, Heather E. McNeely, David Seminowicz, Clement Hamani, Jason M. Schwalb, and Sidney H. Kennedy: "Deep Brain Stimulation for Treatment-Resistant Depression"

The researchers included Helen S. Mayberg of the Rotman Research Institute at Baycrest Centre, University of Toronto, and Emory University School of Medicine; Andres M. Lozano, Clement Hamani, and Jason M. Schwalb from the Toronto Western Hospital Research Institute, University Health Network at University of Toronto; Valerie Voon and Sidney H. Kennedy of the University Health Network at University of Toronto; Heather E. McNeely of Center for Addiction and Mental Health at University of Toronto; and David Seminowicz of the Rotman Research Institute at Baycrest Centre and the Institute of Medical Science at University of Toronto. This study was supported by a distinguished Investigator Award to H.S.M. from the National Alliance for Research in Schizophrenia and Depression (NARSAD).

Publishing in Neuron, Volume 45, Number 5, March 3, 2005, pages 651-660. http://www.neuron.org