While deep brain stimulation (DBS) has a short list of approved FDA indications, the list of potential uses is quite long. At the 2018 meeting of the American Academy of Neurology, Michael S. Okun, MD, Professor of Neurology, University of Florida, discussed what the future of DBS might look like. In his presentation, Novel and Emerging Uses of DBS, he touched on five disorders where much of the current research is focused:
Only a small number of patients with Tourette syndrome (TS) suffer from a refractory or malignant form of the disease that has not shown adequate response to medical or behavioral therapy. As this select group of patients would be the most likely candidates for DBS, available data is limited.
To offset this limitation, the Tourette Deep Brain Stimulation Registry sponsored by the Tourette Association of America tracks data about the use of DBS to help guide the future of DBS for the disorder. It tracks information about targets, devices, immediate results, and results over multiple years. The hope is that as information is added to the registry, a model for the use of DBS in Tourette’s will emerge.
The FDA has actually approved the use of DBS in obsessive-compulsive disorder (OCD) under a humanitarian device exemption, and the results are promising. About two-thirds of the 25 patients who went forward to the FDA for the humanitarian approval were responders to DBS.
The exciting aspect of treating OCD is that these individuals recognize their behaviors as problematic. So after effective treatment, they go back to normal lives. “Their social reintegration is much better than we see in other disorders,” Okun explains. This is an important point to keep in mind for patients who are refractory to medical or behavioral approaches to their disorder—DBS has the potential to truly alleviate suffering in OCD.
Severe, refractory depression represents the largest potential patient pool for DBS. The impact on quality of life, productivity, and the suicide rate makes this an important target for new therapies, including DBS.
But the use of DBS in depression is still investigational. “It’s been reported that up to two-thirds of well-selected patients may benefit, but two large trials by two major manufacturers of devices have ended with negative results,” Okun reports.
He continues, “And what I would argue to us is that perhaps we rushed into a trial without working out the science, thinking ‘Okay, we need to get there, we need to help a lot of people, people are waiting for these therapies.’ Maybe we went a little bit too fast.”
At this early stage, DBS should only be a consideration when medication, psychotherapy, and electro-convulsive therapy have not provided the needed benefit for the patient.
Epilepsy patients have realized some very promising results from DBS. One double-blind, placebo-controlled trial of 110 patients yielded 30% fewer seizures in the treatment group at three months, and a 56 percent reduction after two years.
Exciting ongoing research uses a closed-loop device to sense patterns that lead to a seizure and discharge in response, stopping seizures before they begin.
The recent ADvance trial published in the Journal of Alzheimer’s Disease demonstrated the safety of DBS in these patients, and recommended further study in patients aged 65 and older. Multiple ongoing studies look at the potential uses of DBS in Alzheimer’s.
Outside of the description of investigational uses for DBS, Okun discussed some of the other considerations practitioners must keep in mind when moving forward with DBS—in any disease.
First, he explains, we know a lot about the biological changes from introducing electricity into the brain, even when we don’t understand the mechanism of action. These biological changes can drive innovation in the use of DBS.
This means we have to consider symptoms rather than disorders. “Some of the failures that we see as we try to expand into new indications, may be that we’re lumping everyone together, but it may be that the symptoms, a tic for example versus an obsessive thought versus ADHD, may be very different and in very different places in the brain.” We need to think less in terms of diseases and more in terms of circuits or symptoms, the idea being that devices respond to signals, not diseases.
Another concern is monitoring patients with implanted devices. For some patients, rebounding might be unpleasant, as in a tremor. But for others it might be life-threatening, as in a neuro-psychiatric disorder where suicidal concerns are common. This will be an important job for neurologists as the use of DBS grows.
Finally, off-label indications, or even uses falling under humanitarian device exemptions, aren’t often paid for by insurance. How the initial procedure, follow-ups, new batteries, and the like will be funded for these uncommon situations will be an ongoing issue for patients and physicians alike.
The potential for DBS is great, but at this point care must be taken to move in a systematic manner in an attempt to expand its use. Gathering as much evidence as possible, with particular attention to potential harms will allow this to happen, and it will take everyone involved in the treatment of these patients to achieve this standard.