Unique study of the use of deep brain stimulation

Feb 28 2005

Canadian researchers have seen promising results from a unique study of the use of deep brain stimulation (DBS), in severely depressed patients resistant to standard treatments.

In a study of six patients with severe depression a significant clinical response was seen over a period of six months.

This treatment has previously been used in epilepsy and Parkinson's disease, but is a first in the treatment of depression. High frequency electrical stimulation is targeted at an area of the brain for the purposes of changing that region's activity. Growing evidence of the subgenual cingulated (Cg25) area’s role in depression has made this trial relevant. Dr. Helen Mayberg, a neurologist who is internationally renowned for her studies of depression, now at Emory University School of Medicine in Atlanta states that the hypothesis-driven strategy is particularly important for the treatment of the most severely depressed patients. She teamed up with Toronto Western Hospital surgeon Dr. Andres Lozano, one of the world's authorities on deep brain stimulation and Dr. Sidney Kennedy of UHN an authority on the diagnosis and treatment of mood disorders, the lead psychiatric collaborator.

The six patients, average age 46, from Ontario had failed to respond to a minimum of four different anti-depressant treatments. While there were no serious adverse affects from the experimental DBS treatment, two patients were removed from the study at the six-month point after failing to show a sustained clinical benefit. Mayberg's previous research findings on role of the region Cg25, in healthy mental function produced the hypothesis that this abnormally functioning circuit could possibly be retuned by surgical electrical stimulation, which would produce benefit in patients with refractory depression.

Under local anesthetic two holes were drilled in the skull. Magnetic resonance imaging was used to locate the precise area; two thin wires with electrode contacts were then inserted down to the white matter tracts adjacent to the Cg25 area. Other wires, pushed through the lower neck area were connected to a pulse generator implant that directs an electrical current. The system, "brain pacemaker", is placed under the skin; the most effective voltage, pulse width and frequency is worked out for each patient and their clinical response monitored using brain imaging of the blood flow, in conjunction with neuropsychological tests. This tracking was done at before surgery and at monthly intervals for 6 months.

The team noticed a "striking and sustained remission of depression" in four of six patients who completed the study. The PET scan studies show , not only was over-activity of Cg25 reversed but there were widespread changes in the brain consistent with findings which indicate a positive response to the treatment similar to that seen from medication or psychotherapy in less severely ill patients.

All four patients are still receiving this treatment and continue to experience a remission of their illness.

Dr. Mayberg cautions that the Cg25 DBS study is only a "proof of principle". It is the culmination of 15 years of research using brain imaging technology that has worked to characterize functional brain abnormalities in major depression and mechanisms of various antidepressant treatments.

"We tested the effects of targeted brain stimulation based on our past research findings. We see depression as a complex disturbance of specific circuits in the brain responsible for regulating mood and emotions," says Dr. Mayberg. "This approach is similar to that taken in Parkinson's disease, whereby careful research of the relevant motor circuits, DBS was developed to modulate these dysfunctional circuits and is now used to treat the most severely ill patients. We hypothesized that if DBS could locally modulate a critical node within this mood circuit, such modulation would result in clinical improvement – and it appears it did."

"Our study shows that areas of the brain that are on overdrive in patients with severe depression can be pinpointed, turned down and brought to a more normal level of activity using electrical stimulation," adds Dr. Lozano. "This in turn can lead to a lifting of depression in certain patients."

The study's findings lay the foundation for a larger study to hopefully replicate, refine and extend these first results. "If the safety and benefits we have observed are maintained across other future studies, we could see this approach applied in the years to come as a clinical therapy for patients who fail current treatments and continue to suffer with severe depression," says Dr. Lozano.