Depression: Alternative Treatments – Deep Brain Stimulation (DBS)
Guest: Dr. Ziad Nahas – Psychiatry & Behavioral Sciences, MUSC
Host: Dr. Linda Austin – Psychiatry, MUSC
Dr. Linda Austin: I’m Dr. Linda Austin. I’m interviewing Dr. Ziad Nahas, Associate Professor of Psychiatry here at the Medical University of South Carolina. Dr. Nahas, let’s talk about some very fascinating work that you’re doing in a new technology, DBS, or deep brain stimulation. Can you describe what that technique is?
Dr. Ziad Nahas: This is a neurosurgical intervention by which we implant a pacemaker close to what we typically do with a pacemaker for the heart. But instead of the stimulation being directed at the heart, it’s directed at specific targets in the brain that we believe are involved in regulating mood, and likely to be functioning abnormally, as with severe depression.
Dr. Linda Austin: How extensively tried, at this point, is this technology?
Dr. Ziad Nahas: This is a reasonably young technology in terms of investigating it in depression. To put things in perspective, somewhat, deep brain stimulation has been used for over a couple of decades, if not more, in neurological disorders, like Parkinson’s, for instance, or severe tremors. And there are probably about 30,000 implanted cases worldwide. Whereas when we’re talking about the treatment of depression, we’re only talking, probably, less than 50 worldwide. So, there’s quite a bit of lag behind.
Part of this has to do with the nature of the intervention, given that it’s reasonably invasive. And, also, we really need to remind ourselves that this is for a very special subset of patients that are not your run-of-the-mill depressed patients. So, the level of treatment resistance that they have clearly exceeds simple depression that often, and luckily, does respond to either psychotherapeutic intervention or first-line pharmacological intervention.
Dr. Linda Austin: I see. Can you describe the procedure itself? What could a patient expect?
Dr. Ziad Nahas: This is a brain surgery. So, essentially, after substantial evaluation, patients are often taken to the operating room. And, depending on certain, specific, technological needs, and availabilities, the surgeon would use the patient’s own brain images to try to guide his leads into a specific target. These targets are typically buried deep down into the brain. So then, we’re essentially looking at a wire, one millimeter thick, that we’re driving through from the surface of the brain; roughly, around the top of the head, and you’re kind of driving it into a deeper location.
Dr. Linda Austin: To what structures?
Dr. Ziad Nahas: There have been two or three targets that have been investigated so far. One target is the subgenual cingulate. This is an area that is kind of sitting down at almost the base of the brain, rather medially; so, kind of, almost, at the center. To imagine it, it would be near the bridge of the nose, going farther back; about two inches. Whereas the two other structures that have been looked at are what’s called the internal limb of the internal capsule, which are kind of wide fibers that are kind of connecting the prefrontal cortex to the more emotional part of the brain that is deeply buried. And the third target has been the nucleus accumbens, which in itself is known to be quite involved in the brain’s reward system, energy, and motivation. Investigators in Germany actually went straight to that target. Both the internal capsule and the nucleus accumbens are quite close to each other, so one could argue that, more often than not, even in the internal capsule, that’s primarily what we’re stimulating.
Dr. Linda Austin: So, is this a one-shot stimulation, then, or do they leave the wire in place and continue…
Dr. Ziad Nahas: No, absolutely. Having to go through so much trouble, essentially, we leave wires on each side of the brain. And the wires would be connected to batteries; like generators, that are able to continuously send a certain type of frequency and intensity of stimulation. One could schedule a different pattern. More often than not, actually, stimulation is continuous, and it’s at a high frequency; around 130 Hz. The patient would then notice, probably, some gradual improvement, if not in an on-off type of response, at least in terms of a substantial antidepressant effect. They may have an earlier mood effect, but they don’t seem to be really related to the final outcome measurement.
Dr. Linda Austin: Now, I would assume that the 50 patients on whom this has already been tried had a pretty treatment-resistant depression? Correct?
Dr. Ziad Nahas: Correct.
Dr. Linda Austin: What kind of results have been found with those first 50 patients?
Dr. Ziad Nahas: Well, the first 50 patients have not been implanted all in the same site, with the same investigator, or with the same targets. So, even there, we have slightly different variabilities. I was recently at the American College of Neuropsychopharmacology meeting, and at least one group, from Canada, reported on their 20-patient total, where they were implanted with leads in the subgenual cingulate: Area 25. And there, the investigators are reporting about 60 percent remission at six months, which is a substantially dramatic response, considering that these patients have been known to have failed at least four antidepressants in a current depressive episode. And, really, when you look at it, for somebody to go to that much trouble of undergoing surgery, these are people that have been depressed for 10, 15, 20 years. They’ve tried ECT (electroconvulsive therapy). They’ve tried numerous psychotherapies and medications, and failed, and then had this as, almost, a last resort.
Dr. Linda Austin: And, these are pretty severely depressed patients, too? Is that correct?
Dr. Ziad Nahas: Yes. They are, at the moment, very severely depressed, as well has having shown a lack of response to other treatments.
Dr. Linda Austin: Right. You will be doing a clinical trial, here, with DBS?
Dr. Ziad Nahas: We may be a site for one of the larger multicenter trials. We’re trying to get this approved by the FDA, and this may happen in the next couple of months. We’re also in discussion about a different type of device that would be considered deep brain stimulation, but it also involves an added technology, which is that the wire itself can also record brain activity. And, to the extent that we begin understanding the brain state that’s signaling depression, we may be able to better find treatments. So, it’s not just continuously stimulating, but stimulating and listening back, and trying to ultimately guide the treatment with a better individuation given each patient’s own brain activity.
Dr. Linda Austin: Now, are you certain that this will happen, or we might become a site?
Dr. Ziad Nahas: With the first one, we might be a site. For the second one, the responsive neurostimulation, this will take place in the summer.
Dr. Linda Austin: I see. Will these be placebo-controlled trials? In other words, if you participate, might you get a sham treatment, as opposed to the real thing?
Dr. Ziad Nahas: The first one, for sure. The first part of the treatment is going to consist of at least three to four months of the individual not knowing whether they’re being stimulated with the active treatment, or they won’t have their device turned on. However, after that initial period, they will definitely have an opportunity to be exposed to the real treatment, and that’s almost certain.
Dr. Linda Austin: Very exciting. Thank you so much for talking with us today.
Dr. Ziad Nahas: You’re welcome.
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