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Deep Brain Stimulation for Treatment-Resistant Depression Part 1

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Posted on November 21, 2016 - 3:59pm

Written by Colton Smith

In April 2016 I attended the Symposium on Neuroethics hosted by the State University of New York Downstate Medical Center. Here Neurologists and Neuroscientists discussed emerging neurotechnology and how it’s being implemented. While at this conference I had the pleasure to speak with Dr. Helen Mayberg. She is a professor of psychiatry, neurology, and radiology and the Dorothy Fuqua Chair in Psychiatric Neuroimaging and Therapautics at Emory University. Her research takes an interdisciplinary-approach to integrate cutting-edge imaging strategies, quantitative behavioral and psychophysiological metrics, and experimental treatment trials to define brain-based biomarkers that can optimize treatment selection for individual patients.

Depression in the brain. Courtesy of Mark George, M.D., NIMH.

Depression in the brain. Courtesy of Mark George, M.D., NIMH.

Colton Smith- We’ve been here all day at the neuroethics symposium and we’ve been discussing emerging neurotechnology.  My first question is how do you make the decision to implant a deep brain-stimulating device for treatment of depression? Does the patient have to be considered treatment resistant?

Dr. Helen Mayberg- Deep brain stimulation (DBS) is a technology reserved for people who have actually failed to respond to any and all conventional treatment.

Smith- So the patient has to fail to respond to medication?

Mayberg- It’s not just medicine that the patient has to fail to respond to. We require that people fail four different classes of medication, fail an evidence-based psychotherapy, and fail to respond to or do not tolerate electroconvulsive therapy. Before we even consider using deep brain stimulation these people must fail to get better or maintain a response to any of those treatments.

Smith- Why is DBS used as a last treatment strategy after everything else has failed? If deep brain stimulation is such a revolutionary technology, then why isn’t it used as the first strategy?

Mayberg- It’s not the first strategy because for most patients a depressive episode will spontaneously go away or will respond to other less-invasive treatments. In medicine you want to work from the most straightforward to the most complex in terms of using treatments, but fundamentally, we are missing the critical piece, which is how to match the best treatment to a given individual.  You’d like to think that you could start with no medication at all—using psychotherapy, ramp up to medication, and then finally progress to medications that are harder to take and may have more side effects, and if those fail to use electroconvulsive therapy or some of the newer neuromodulation strategies. That might be an effective route for you, but not for someone else.  You’re always trying to weigh in the care of any one patient and what will work for them. Unfortunately we don’t have biomarkers that tell us what type of depression a person has and the type of therapy required to treat it.  So the best we can do now is to use clinical algorithms that steps through various established treatments moving to those that are more difficult to use when more straightforward or first line approaches are ineffective. Our research has demonstrated that response to certain treatments can be predicted by the patterns of brain activity measured prior to initiating treatment. The activity in one specific brain area, the anterior insula, has shown in our initial studies to track with treatment outcome to either medication or cognitive behavior therapy.  If the insula is overactive -- medication gets you well, while therapy has no effect. The opposite is seen if you have an underactive insula -- you do great with therapy, but drugs are ineffective. The notion that everyone with depression should follow the same treatment is a nice idea, but it’s not practical. Like with other medical diseases, biomarkers can help to match a patient to the treatment that is best for their illness. That’s the goal.  

Smith- You were mentioning in your talk that the people who are treatment-resistant have certain abnormalities in their brains that are correlated with that. Could you talk a little bit about that?  

Mayberg- With these very refractive patients we’ve had some success with brain stimulation.  We’ve identified a target to stimulation—the subcallosal cingulate region-- and the white matter tracts or roadways that pass nearby that we need to stimulate to facilitate and maintain a significant antidepressant response.  The next step in the research is to identify which treatment resistant patients are most likely to respond to this type of DBS.  These imaging studies complement our imaging biomarkers studies with less treatment-resistant patients. At issue is to match a patient to the best treatment at all stages of illness. Treatment resistant depression isn’t one entity either. We need to take these patients who’ve gotten better from DBS and try to understand how their brains are different from the people who responded to more conventional forms of medication as well as to patients who fail DBS. Over the last 30 years of people studying depression there’s consistently been findings indicating low activity in the frontal lobe of patients who suffer from depression. But some patients have been found to have high activity in their frontal lobe. That doesn’t invalidate the low activity patients, it just means that the frontal lobe probably isn’t the source of the problem. Something else is causing frontal lobe activity to turn up or down, just like something is causing the insula to have increased or decreased activity. What we’ve discovered is that there are some abnormalities in certain roadways that are shared between all kinds of depression, but there are some unique abnormalities that appear only in the treatment-resistant group.

Smith- So they have some similarities, but you can’t really group these different types of depression into the same category?

Mayberg- Exactly. You know, for many of these treatment resistant patients they look like our patients who got better on therapy or drugs. There’s something about their illness that causes them to go off the rails. They can be successfully treated and move along with their life and then all of a sudden have another episode of depression. Depression is generally an episodic illness. Patients may have over the course of their lives 3, 4, or 5 episodes of depression. In the epidemiology literature many people have a single episode and that’s it. This single episode can be a life event that eventually gets resolved and everything is fine. Once you’ve had two episodes though, the likelihood of having a third is a lot higher. That’s why you tend to keep people on treatment long-term. I mean, the fact that in one depressive episode you got better on therapy and in another depressive episode you got better on drugs is telling us something about the nature of the depressed brain and how it can evolve to need more and more aggressive treatments.

This blog post is in connection with the closed scientific workshop in partnership with the National Institutes of Health that was held to spark discussions of big, unanswered questions on how the brain and machines process patterns, aimed at understanding consciousness, intelligence, and madness. Also related is the Origins Dialogue with Johnny Depp and Lawrence Krauss on Finding the Creativity in Madness.

Read part 1 of this blog series, Deep Brain Stimulation for the Minimally Conscious Part 1

Read part 2 of this blog series, Deep Brain Stimulation for the Minimally Conscious Part 2

Read part 4 of this blog series, Deep Brain Stimulation for Treatment Resistant Depression Part 2