Pittsburgh, November 15, 2007 -- An implanted cortical stimulation device may help decrease the severity of depression and increase psychological function in patients suffering from major depressive disorders, according to preliminary findings from a Phase 1 feasibility study conducted at the University of Pittsburgh and two other institutions nationwide.

The FDA-approved PROSPECT study involved the implanting of Northstar Neuroscience’s Renova™ Cortical Stimulation System investigational device delivering targeted electrical stimulation to the outer surface of the brain—the prefrontal cerebral cortex. Department vice chairman of education, Douglas Kondziolka, MD, and Robert Howland, MD, of the department of psychiatry were co-investigators in the study. The first study patients were evaluated and had surgery by the University of Pittsburgh team.

Renova™ Cortical Stimulation Device (Courtesy Northstar Neuroscience)

The PROSPECT study was designed to assess the basic safety and effectiveness of cortical stimulation for patients diagnosed with major depressive disorder. The patients in the PROSPECT study were not responsive to an average of nine previous antidepressant treatments and endured their current depressive episode for an average of seven years. Ten of the 12 patients were treated previously with electroconvulsive therapy. Thus, this represented a subset of patients with a severe depression history.

After a baseline observation period, five patients received active cortical stimulation during the first eight weeks, while five patients received sham stimulation. After the initial eight-week period of sham stimulation, these patients also received active stimulation.

Initial findings at the eight-week primary endpoint show the Hamilton Depression Rating Scale (HDRS; an established scale used to rate the severity of a patient’s depression) scores of the active cortical stimulation patients improved an average of 24% from baseline. In contrast, only a 3% improvement in HDRS scores from baseline was reported in patients in the sham group. After eights weeks of active stimulation in ten patients, 20% achieved an improvement of 50% or more in HRDS score.

Additionally, after the ten patients received 16 weeks of active stimulation, HDRS scores improved by an average of 27% from baseline and the Montgomery-Asberg Depression Rating Scale (MADRS; another established scale used to rate the severity of a patient’s depression) scores improved by 31% from baseline. The Global Assessment of Functioning (GAF; a scale used to rate the social, occupational and psychological functioning) scores improved by 50% from baseline, indicating an improvement in patient’s quality of life and ability to function. Each of these rating scales indicated a continuing trend of improvement at 16 weeks.

There have been no device related serious adverse events during the study. Primary endpoint results on all patients enrolled in the study will be reported later this year. All surgeries were performed without incident.

“These early findings in this very severe group are encouraging and suggest that cortical stimulation holds promise for individuals with major depressive disorder who have endured numerous unsuccessful treatments such as antidepressants or electroconvulsive therapy,” said co-investigator Brian Kopell, MD of the Medical College of Wisconsin’s Department of Neurosurgery who presented the initial findings recently at the Congress of Neurological Surgeons in San Diego.

“The inherent advantage of cortical stimulation for continuous, long-term relief of depressive symptoms is its ability to modulate neural function without surgically penetrating brain tissue. This results in a shorter procedure and relatively quick recovery time.”

According to the study’s documentation, major depressive disorders are the most common of all psychiatric disorders. The World Health Organization estimates that 340 million people worldwide suffer from an episode of major depression each year, accounting for 4.4% of the overall global disease burden. In the United States, about 9.5% or 19 million people are affected by a depressive disorder, with a lifetime risk of about 17% for a major depressive disorder.

While depression can be effectively treated in the majority of patients by medication and psychotherapy, up to 20% of patients fail to respond. electroconvulsive therapy (ECT) is effective in approximately 70% of cases where antidepressant medications do not provide sufficient relief of symptoms. However, as many as 20-50% of the people who respond well to a course of ECT relapse within six months, therefore, periodic maintenance therapy is often required.

For those patients who are resistant to the therapies noted above, more invasive approaches have been used, including Vagus Nerve Stimulation (VNS) and more recently Deep Brain Stimulation (DBS).

Direct cortical stimulation of the cortex via an implanted device system may provide long lasting benefit with minimal side effects. The PROSPECT study seeks to assess the safety and efficacy of this approach.

In addition to the University of Pittsburgh and the Medical College of Wisconsin, physicians at Massachusetts General Hospital in Boston also participated in the study.