From The Quarterly, Spring 2012

The first placebo-controlled trial to verify the effectiveness and safety of deep brain stimulation (DBS) as a treatment for severe, treatment-resistant depression was reported by a team led by NARSAD Grantee Paul E. Holtzheimer, M.D., and Brain & Behavior Research Foundation Scientific Council Member Helen S. Mayberg, M.D. The trial was also the first to test DBS as a treatment for patients with bipolar disorder, who responded as positively as the patients in the study with major depressive disorder, or unipolar depression.

In DBS, high-frequency electrical stimulation is targeted to a specific area of the brain through electrodes implanted in the brain and connected to a pulse generator implanted in the chest. DBS is currently used to treat Parkinson’s disease, other medication-refractory movement and obsessive-compulsive disorder. In a pilot study initially published in 2005, with long-term results published in 2008 and 2011, Dr. Mayberg pioneered DBS to treat intractable unipolar depression. She used DBS to target the subcallosal cingulate or Brodmann Area 25, an area she earlier identified to be linked with the pathophysiology of depression. The results of the current trial were announced in the February 2012 issue of the journal Archives of General Psychiatry.

Concerning the new findings, Dr. Mayberg states: “We were particularly happy to see that bipolar patients responded as well as unipolar patients because bipolar disorder is notoriously hard to treat.” Importantly, DBS did not trigger manic episodes in the bipolar patients as can occur following other forms of antidepressant treatments; and there were few adverse side effects for any of the patients in the study.

Seventeen patients were enrolled in the study, 10 with unipolar depression and seven with bipolar disorder. As placebo control, they received sham stimulation for four weeks which was followed by active and continuous DBS. They were then evaluated at periods up to two years. The results showed that a significant decrease in depression and increase in function were associated with continuing stimulation. Remission and response rates were 18 percent and 41 percent respectively after 24 weeks; 36 percent and 36 percent after one year. After two years of stimulation, 92 percent of the patients reported significant relief, and 58 percent were in remission. Those who achieved remission did not relapse.

Dr. Mayberg is a NARSAD Young, Independent and Distinguished Investigator Grantee and Brain & Behavior Research Foundation Scientific Council Member. She is a professor in the departments of psychiatry and behavioral sciences and neurology at Emory University School of Medicine. Dr. Holtzheimer, who was mentored by Dr. Mayberg and authored the recently published study, is a NARSAD Young Investigator Grantee and Associate Pro-fessor and Director of the Mood Disorders Service at the Geisel School of Medicine at Dartmouth. The research team included colleagues from Emory and Dartmouth as well as the University of Denver, Cleveland Clinic and the University of Pittsburgh.

While the results of the trial are extremely promising, Dr. Holtzheimer stresses that DBS treatment for depression is still in the experimental phase. “Only small studies have been done to date,” he explains. “We need to see large, multi-site trials to further verify efficacy and safety.”