A study conducted at Emory University over the course of several years found that Deep Brain Stimulation (DBS) of an area in the brain called the Subcallosal Cingulate (SCC) provides a robust antidepressant effect and that the effect is sustained over a long period of time. The participants were all patients with treatment-resistant depression—the most severely depressed patients who have not responded to other treatments.
The long-term (4-8 years) data presented in this study validates earlier work conducted by the research team. It also lays the foundation for additional studies to refine and optimize DBS for these patients. The research was led by Helen S. Mayberg, MD, now Professor of Neurology, Neurosurgery, Psychiatry, and Neuroscience, and Founding Director of the Nash Family Center for Advanced Circuit Therapeutics at the Icahn School of Medicine at Mount Sinai, and has been published in The American Journal of Psychiatry.
At the moment, DBS is a treatment approved by the U.S. Food and Drug Administration for essential tremor, Parkinson’s disease, epilepsy, and obsessive-compulsive disorder. It is a neurosurgical procedure that involves the placement of a neurostimulator (sometimes referred to as a “brain pacemaker”) on the brain. The device sends high-frequency electrical impulses through implanted electrodes deep in the brain to specific brain areas responsible for the symptoms of each disorder.
Stimulation alone is not the only direction the field is moving. Researchers have also built a flexible brain implant that records neural activity, stimulates neurons with light and delivers drugs through one thin fiber, though it has only been tested in mice and is years from clinical use.
Dr. Mayberg also led the first trial of DBS in 2005. Her team was testing the effects of DBS on the SCC white matter (known as Brodmann Area 25) of patients with treatment-resistant depression. The antidepressant response wasn’t significant enough by the designated six-month predicted time scale, so the trial was halted early. However, the team did carry on with a smaller cohort of 28 patients from this study.
Dr. Mayberg said:
“Despite the fact that larger trials were halted early, what my colleagues and I were seeing as we continued to follow patients from our initial trials was that over time, they were getting better and not only that, they were staying better. So, we stayed the course.
Over eight years of observation, most of our study participants experienced an antidepressant response to the deep brain stimulation of Area 25 that was robust and sustained. Given that patients with treatment-resistant depression are highly susceptible to recurrent depressive episodes, the ability of DBS to support long-term maintenance of an antidepressant response and prevention of relapse is a treatment advance that can mean the difference between getting on with your life or always looking over your shoulder for your next debilitating depressive episode.”
Figures from the outcome of the 28 patients enrolled in the open-label clinical trial of SCC DBS for treatment-resistant depression show that response and remission rates were maintained at or above 50% and 30%, respectively, through years 2-8 of the follow-up period. Overall, 21% of the participants demonstrated a continuous response to treatment from the first year forward. Furthermore, the data supports the long-term safety and sustained efficacy of SCC DBS for treatment-resistant depression.
Andrea Crowell, MD, Assistant Professor of Psychiatry and Behavioral Health Sciences at Emory University School of Medicine, said:
“While clinical trials generally are structured to compare active and placebo treatments over the short term, our research results suggest that the most important strength of DBS in this hard-to-treat clinical population lies in its sustained effects over the long term. For people suffering from inescapable depression, the possibility that DBS can lead to significant and sustained improvement in depressive symptoms over several years will be welcome news.”
The process of the study involved participants being seen by a study psychiatrist weekly for 32 weeks, starting at least four weeks prior to surgery where they received the implant. Visits were then narrowed down to every six months for years 2-8 of the study. Of the 28 participants, 23 patients continue in long-term follow-up.
Dr. Mayberg concluded in a press release:
“At the Center for Advanced Circuit Therapeutics at Mount Sinai, we are currently gearing up for the next phase of this research, now funded by the National Institutes of Health Brain Initiative. Our new study will recruit treatment-resistant depression patients, as before, but they will be implanted with a new research prototype DBS system (Summit RC+S) that allows simultaneous recordings of brain activity directly from the site of stimulation during active DBS therapy. Advanced imaging, behavioral, and physiological assessments will also be performed at regular intervals in the lab.
These studies will provide an unprecedented opportunity to monitor the trajectory of recovery over days, weeks, and months at the neural level. Building on preliminary findings from Emory, we anticipate that these brain signatures will provide important new insights into DBS mechanisms and, importantly, will help guide future decisions about DBS management that can further optimize clinical outcomes in our patients.”
The team is continuing the research with more patients. They hope to soon be able to help people who are unaffected by all the other therapy options available.
