Deep Brain Stimulation Shows Promise in Severe, Refractory Depression

Caroline Cassels

April 30, 2008

April 30, 2008 (Chicago, Illinois) — New research suggests that bilateral deep brain stimulation (DBS) may be an effective treatment option for patients with severe, refractory, major depression.

Presented here at the American Association of Neurological Surgeons 76th Annual Meeting, Ali Rezai, MD, PhD, director of the Cleveland Clinic's Center of Neurological Restoration, in Ohio, presented the results of the prospective, open-label multicenter study, which showed that half of the 17 subjects achieved a 50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to 1-year follow-up.

Further, the investigators reported that study subjects experienced progressive improvement in mood over time as well as discernible improvements in social and occupational functioning.

"These are patients who have been completely disabled by depression. They have failed every available treatment, including medication, electroconvulsive therapy [ECT], and, in some cases, even other surgical treatments. Yet with this pacemaker technology, they have been able to make significant strides," Dr. Rezai, who is a neurosurgeon, told Medscape Neurology & Neurosurgery.

"Remarkable" Results

Study coinvestigator Donald. A. Malone, MD, director of the Cleveland Clinic's Psychiatric Neuromodulation Center, agreed and described the results of this pilot research as unprecedented in this patient group.

"Working in a tertiary-care center that treats large numbers of these resistant patients, it has been my experience that this severe, refractory population just doesn't get well very often. So to see improvement in an significant percentage of these individuals, to me, is remarkable," he said in an interview with Medscape Neurology & Neurosurgery.

Encouraged by their research results examining the effect of DBS in refractory obsessive-compulsive disorder (OCD) patients, which began in 2001, the investigators launched the current study in subjects with major depression in 2003.

"We noticed in our OCD patients, many of whom also had depression, that their mood substantially improved with deep brain stimulation. So, based on this observation and the fact that the particular area of the brain we were targeting, the ventral capsule/ventral striatum [VC/VS], is implicated in depression and anxiety disorders, we went ahead and started this study in patients with severe depression," said Dr. Malone.

A total of 17 patients with severe, refractory depression from 3 centers--including the Cleveland Clinic; Brown University, in Providence, Rhode Island; and Massachusetts General, in Boston--were enrolled in the study between 2003 and 2007 and underwent bilateral DBS implantation of the VC/VS under high-resolution magnetic resonance imaging.

To be eligible for the study, individuals had to have severe and disabling major depression for a minimum of 5 years with symptoms refractory to at least 3 classes of antidepressants titrated to the maximal tolerated doses. In addition, they had to have failure of combined therapy with at least 2 augmentation agents and multiple failed ECT trials and no imminent risk of suicide.

The mean duration of illness was 21 years. On average, patients had 6 antidepressant trials, 6 augmentation trials, and more than 30 ECT treatments before trial enrollment.

Progressive, Durable Effect

Once the surgery was completed, programming of the device was done by a single psychiatrist at each site in an outpatient setting.

Patients completed standard preoperative, baseline, and regular-interval postoperative neurological, psychiatric, and neuropsychological assessments to determine impact on quality of life, functioning, and cognitive status.

To date, 16 of the 17 patients have been followed for a minimum of 1 year with a mean follow-up of 22.8months. The criterion of a decrease in the MADRS score of at least 50% compared with baseline was met by 8 of 17 patients at 6-month follow-up and by 8 of the 16 patients at 12 months.

Half of the study group met the strict responder criteria, with some patients experiencing up to a 70% improvement. However, even among patients who were "nonresponders," there was a 30% improvement in symptoms.

According to Dr. Rezai, other benefits reported by patients, their families, and psychiatrist included improved interpersonal connectivity and their interaction with family and friends. "These patients were able to enjoy many aspects of life again that they had lost because of depression," he said.

Furthermore, 30% of the responder group is currently in remission. "We've shown that up to this point this treatment has a progressive and durable effect," said Dr. Rezai.

If further study confirms these results, Drs. Rezai and Malone note that DBS has the potential to help large numbers of patients.

According to the researchers, approximately 2 to 3 million patients in the United States will develop severe refractory depression, and 15% of these individuals will attempt suicide.

The study was funded by Medtronics. Drs. Rezai and Malone report receiving research support and/or honoraria and consulting fees from Medtronics.

American Association of Neurological Surgeons 76th Annual Meeting: Abstract 703. Presented April 29, 2008.

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