Deep brain stimulation may help people with treatment resistant major depression

Researchers from the Cleveland Clinic, Brown University, and Massachusetts General Hospital will present results of a long-term outcome study that builds on previous promising research, which has shown that deep brain stimulation (DBS) is a potentially effective treatment option for people with treatment resistant major depression.

The World Health Organization rates major depression as the top cause of disability worldwide. While many patients with major depression find relief through a combination of psychotherapy and medication, some people are left severely disabled. 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.

DBS surgery involves the placement of tiny implantable electrodes into specific parts of the brain that are functioning abnormally. These electrodes emit tiny pulses of electrical stimulation to block the abnormal activity in the brain, which causes a variety of symptoms - such as pain, tremors, movement problems; as well as obsessions, moods and anxieties associated with psychiatric disorders. The success of DBS is dependent on the surgical team's ability to precisely pinpoint the specific brain area for stimulation. The advantage of DBS is that it is reversible, nondestructive, and can be modified by adjustment of the stimulator settings after implantation.

Ali R. Rezai, MD, director of Cleveland Clinic's Center for Neurological Restoration, and a multi-center team of investigators were inspired by the success of DBS in treating the tremors associated with Parkinson's and movement disorders like dystonia and essential tremor. "Starting in 2001, we began treating patients with obsessive compulsive disorder (OCD) with promising outcomes. These findings resulted in the initiation of a subsequent trial for patients with severe and medication intractable major depression, starting in 2003," stated Dr. Rezai.

"The preliminary results of research undertaken between 2003 and 2005 indicated that bilateral DBS of the anterior limb of the internal capsule holds promise for the treatment of intractable major depression, which led to the more extensive research results being presented today," added Dr. Rezai.

The results of the current study, Deep Brain Stimulation for the Treatment of Depression: Long-Term Outcomes from a Prospective Multi-Center Trial, will be presented by Dr. Rezai, from 10:30 to 10:44 a.m. on Tuesday, April 29, 2008, during the 76th Annual Meeting of the American Association of Neurological Surgeons in Chicago. Co-authors are Linda Carpenter, MD, Darin Dougherty, MD, Emad Eskandar, MD, Gerhard Friehs, MD, Cynthia Kubu, PhD, Andre Machado, MD, PhD, Paul Malloy, PhD, Donald Malone, MD, Lawrence H. Price, MD, Steven Rasmussen, MD, Scott Rauch, MD, Stephen Salloway, MD, and Audrey Tyrka, MD, PhD. This multidisciplinary group consists of close collaboration between neurosurgeons, psychiatrists and psychologists from these institutions.

Fifteen chronic and severely depressed patients were enrolled in this study. These patients had failed multiple medication trials, as well as psychotherapy and electroconvulsive therapy (ECT). These highly intractable and often suicidal patients underwent bilateral DBS implantation in the ventral internal capsule/ventral striatum (VC/VS) at the three institutions.

The Montgomery-Asberg Depression Rating Scale (MADRAS) was the primary outcome scale, among many scales, including those assessing overall quality of life, functioning and cognitive status. The outcome raters were blinded to the DBS status of the patient. Follow-up ranged from six to 48 months, with a duration of one year or longer in 11 of the 15 patients. Responder criteria was defined by this study as a 50 percent decrease in MADRAS scores. The following outcomes were noted:

• Responses were seen in seven (47 percent) of 15 patients at six months, five (45.5 percent) of 11 at 12 months, and eight (53.3 percent) of 15 at last follow-up.
• Long-term improvement in depression severity, functioning, and quality of life were all noted.
• Measures of short-term memory improved.
• There were no hemorrhages, infections or other neurological deficits.

"This research substantiates our earlier findings, which indicate that bilateral DBS of the anterior limb of the internal capsule holds promise and hope for select patients suffering from severe and treatment resistant major depression, stated Dr. Rezai. "While about half of this patient group responded to treatment, I feel that as we learn more about this rather new technology, efficacy will continue to improve. It is important to understand that this treatment is not for everyone with major depression and only for those that have tried various medications, psychotherapy and ECT. But, nevertheless, it is very promising news for the many suffering patients and their family members that have virtually given up hope."

Results of the OCD study, Deep Brain Stimulation of the Ventral Internal Capsule/Ventral Striatum for Obsessive-Compulsive Disorder (OCD): World-Wide Experience, will be presented by Dr. Rezai, one day prior to the depression study, 2:45 to 2:59 p.m., Monday, April 28. While OCD is not as prevalent as depression, it does affect 2 to 3 percent of the United States population, and at least 10 percent of patients have disabling cases that are resistant to treatment. The results reveal meaningful symptom reductions and functional improvement in about two-thirds of highly resistant patients after open treatment. Recent improvements in outcomes have been achieved through refinements in targeting areas. This is a worldwide cooperative prospective study involving the largest number of severe and intractable OCD patients with long-term follow-up with DBS.

Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 7,200 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.