What’s next for deep brain stimulation in OCD?
VIENNA – Even though deep brain stimulation has been used to treat obsessive-compulsive disorder in fewer than 300 patients worldwide, the therapy has had a huge impact on understanding of the disorder, Damiaan Denys, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.
Indeed, the efficacy of deep brain stimulation (DBS) in the most severe, treatment-refractory cases of OCD casts doubt upon the fundamental construct clinicians have relied upon for decades to comprehend OCD: Namely, that affected patients first experience obsessions, which induce anxiety, which then stimulates compulsions, and engaging in those compulsions brings relief and reward, and then the whole cycle starts over again.
That construct may not actually be true.
“Deep brain stimulation will force us to rethink OCD,” predicted Dr. Denys, professor and head of psychiatry at the University of Amsterdam.
What does DBS change, and is there a temporal order? It varies, the psychiatrist said.
“In some patients, anxiety is the first thing that changes. In others, it starts with obsessions. Compulsions do decrease, but it’s difficult. It takes some time, and often we need supplemental cognitive-behavioral therapy (CBT). What changes, mainly, in my experience, is not symptoms, but something outside of OCD: namely, mood. Deep brain stimulation has a huge impact on mood. That’s an interesting finding, because it suggests the possibility that you can change a psychiatric disorder by changing symptoms that are thought of as being outside the disorder,” Dr. Denys observed.
“Another interesting thing is that deep brain stimulation changes things that are not even within psychiatry. When we ask our patients what has been the most profound impact deep brain stimulation has had on their lives, all of them say, ‘It increases my self-confidence.’ And that’s not something that is included in our scales. We assess patients using the HAM-D [Hamilton Rating Scale for Depression] and Y-BOCS [Yale-Brown Obsessive Compulsive Scale] and other measures, but there are still some very important aspects we are not taking into account and that have a profound effect on symptoms. In this case, using deep brain stimulation, we improve self-confidence and thereby change a whole chain of symptoms,” he continued.
Among the 60 highly refractory OCD patients treated by DBS by Dr. Denys and his colleagues at the Amsterdam center over the past 15 years, 15% were cured as a result.
“I purposely use the word ‘cured,’ because they don’t have obsessive-compulsive symptoms, anymore, which is, of course, extraordinary,” Dr. Denys noted.
An additional 35% of patients had a good response, defined as 60%-80% improvement on the Y-BOCS. Ten percent of patients were partial responders, with a 20%-40% improvement on the Y-BOCS. And 15% were nonresponders.
Closed-loop system coming
DBS entails implantation of electrodes deep within the brain to interrupt dysfunctional brain signals in local areas and across neural networks. This dysfunctional brain activity is expressed as symptoms. To date, DBS has been used in what’s called an open-loop system: Patients report the symptoms they’re experiencing and the clinician then adjusts the electrode settings in order to quell those symptoms. This approach is about to change. The technology has improved vastly since the early days, when the electrodes had four contact points. Now they have 64 contact points, and are capable of sending and receiving electrical signals.
“The next step in deep brain stimulation will be a closed-loop system. We will remove the clinician and the patient, and attempt to use a device capable of recording what happens in the brain and then changing electrical activity in response to the recordings. Our purpose will be to block these brain signals in advance of obsessions and compulsions so patients don’t have these symptoms. It’s technically possible. It has been done in Parkinson’s, and I think it’s the next step in psychiatry,” Dr. Denys said.
Indeed, he and his coinvestigators are planning formal studies of closed-loop DBS. For him, the prospect raises three key questions: What are the neural correlates of OCD symptoms? What about the ethics of implanting a device in the brain which by itself results in different life experiences? And will closed-loop DBS have superior efficacy, compared with open-loop DBS?
“How is the mind rooted in the brain, and how is the brain expressed in the mind? It’s the most fascinating question; it’s why we all love psychiatry, and up until now, there are no answers,” he observed.
Significant progress already has been made on the neural correlates question. Dr. Denys and his colleagues have found that when OCD patients with deep brain electrodes engage in cleaning compulsions, their local field potentials in the striatal area show peaks of roughly 9 Hz in the alpha range and in the beta/low gamma range. These patterns may represent compulsive behavior and likely could be useful in steering a closed-loop system. Also, the Dutch investigators have found that 3- to 8-Hz theta oscillations in local field potentials in the striatal area may represent a neural signature for anxiety and/or obsessions.
Using a closed-loop system, he continued, investigators plan to test two quite different hypotheses about the fundamental nature of OCD. One is that obsessions, anxiety, compulsions, and relief are each separately related to different brain areas. The other hypothesis is that one central brain stimulus drives the chain of symptoms that characterize OCD, and that by identifying and blocking that primary signal, the whole pathologic process can be stopped.
