The World Health Organization rates major depression as the top cause of disability worldwide, with an estimated 340 million people suffering from an episode of major depression every year. While most patients with major depression find relief through a combination of psychotherapy and medication, about 20 percent of patients fail to respond. Patients who are most resistant to medications, psychotherapies, and electroconvulsive therapy (ECT) have little hope of recovery, and suffer a heightened risk of suicide and mortality. Sadly, statistics show that the suicide rate in people with major depression is as high as 15 percent.

Electroconvulsive therapy (ECT) is effective in approximately 70 percent of cases in which antidepressant medications do not provide adequate relief of symptoms. However, as many as 20 to 50 percent of patients who initially respond well to ECT treatment, suffer a relapse within six months, therefore, periodic maintenance therapy is often required. For those patients who are resistant to these therapies, more invasive approaches have been used, including vagus nerve stimulation and more recently, deep brain stimulation.

Researchers at three U.S. institutions investigated the use of a new form of stimulation in patients with medically refractive major depression. The results of this study, Long Term Follow-up of Cortical Stimulation to Treat Major Depressive Disorder, will be presented by Emad N. Eskandar, MD, Masachusetts General Hospital/Harvard Medical School, 10:30 to 10:44 am, Tuesday, May 5, 2009, during the 77th Annual Meeting of the American Association of Neurological Surgeons in San Diego. Co-authors are Douglas Kondziolka, MD (University of Pittsburgh Medical Center), and Brian Kopell, MD (Medical College of Wisconsin).

“Imaging and transcranial magnetic stimulation studies have demonstrated that the left dorsolateral prefrontal cortex (DLPFC) area of the brain plays a critical role in patients with major depressive disorder (MDD). These findings prompted research in which we used an investigational epidural cortical stimulation system to deliver targeted stimulation to the left DLPFC in 12 patients with MDD,” stated Dr. Eskandar.

The 12 patients were randomized to single blind active or sham stimulation for 8 weeks, and then all subjects received active stimulation. One patient was excluded from analysis due to a protocol deviation. During the procedure, the electrodes were placed epidurally, outside the dura, through a small craniotomy. Outcome assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HDRS), and the Global Assessment of Functioning (GAF). The following results were noted:

•At 8 weeks, HDRS decreased by 22 percent (active: n=6) versus 3 percent (sham: n=5).

•MADRS decreased 22 percent (active) versus 8 percent (sham).

•GAF increased 23 percent (active) versus 12 percent (sham).

•In all patients, continued improvement was seen at 6 months (average HDRS: 20 percent) and 12 months (average HDRS: 33 percent).

•At 12 months, patients whose electrodes were implanted >20 mm from the precentral sulcus averaged a 59 percent improvement in HDRS compared to a 12 percent improvement in patients (n=6) with electrodes <20mm from the precentral sulcus.

•Four patients with electrodes <20mm from the precentral sulcus elected electrode revision surgery.

“The advantages of cortical stimulation are that it is reversible, nondestructive, less invasive than other forms of stimulation, and can be modified by adjustment of the stimulator settings after implantation. We observed that the position of the electrodes in relationship to the precentral sulcus played an important role in patient outcome. This small study is promising, suggesting that cortical stimulation has potential as a viable treatment option for patients with severe treatment-resistant MDD. The next step is to proceed with a larger multicenter trial,” concluded Dr. Eskandar.

The author reports no conflicts of interest.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 7,400 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.

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Source: American Association of Neurological Surgeons (AANS)