“A Little Bit Science, A Little Bit Manifesto”: Deep Brain Stimulation in Psychiatry

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CONFERENCE REPORTER
“This talk is going to be a little bit science a little bit manifesto. Let’s talk about invasive technologies and deep brain stimulation (DBS),” said Alik Widge, MD, PhD, by means of opening his session, “Deep Brain Stimulation in Psychiatry: Physiology, Psychometrics, & Plasticity,” at the American College of Neuropsychopharmacology 2023 Annual Meeting. “I want to use this podium to remind people is invasive technologies, particularly DBS, do work.”

Although it has impressive results in open-label psychiatric trials, DBS has struggled to scale to and pass through multi-center randomized trials for major depressive disorder (MDD),^1,2 shared Widge. Without success in these trials, US Food and Drug Administration approval, as well as insurance coverage, is not possible.

The fundamental problem is therapeutic target engagement, as DBS is a complex technology and hard to get right for each individual. Challenges include:

-Selecting patients

-Identifying and engaging target brain circuits

-Maintaining engagement/response over time

Part of the problem, explained Widge, is patient-specific anatomic targeting, specifically optimizing white matter network targeting. “In expert hands, patients are going to get better. We see response rates at greater than 80% and they are durable. Additionally, timing can completely change the effects that you get in the brain and, in some cases, can lead to long term lasting change,” said Widge.

Furthermore, psychiatric application of DBS does not have immediate indicators. In Parkinson disease, where DBS is a commercial success, reasonable DBS settings cause the essential tremor to stop immediately. Proof of success is as easy as asking the patient to hold up their hand. While there is evidence of some positive emotional responses upon initiating DBS in psychiatric disorders like MDD, such a response does not predict sustained success.

Clinical evidence also shows some preliminary efficacy of DBS in other disease states, such as obsessive-compulsive disorder, addiction, and eating disorders. To Widge, this shows that psychiatric disorder symptoms could be comprised of “functional domains.” These domains can be tracked to specific brain areas which can then be targeted via DBS.

“There must be some underlying transdiagnostic dysfunction that happens in all of these disorders that is highly linked to the circuits that are caught in that electric field. Almost all of these disorders involve response indication deficits and failures of the construct of cognitive control—the ability to switch and modulate one's behavior adaptively,” said Widge.

Widge also suggested that neuroplasticity may hold the key to long-term efficacy of DBS in psychiatric disorders like MDD. He anticipates understudied targets and parameters may pose challenges as we move forward with potential plasticity-centered DBS.

References

1. Holtzheimer PE, Husain MM, Lisanby SH, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry. 2017;4(11):839-849.

2. Dougherty DD, Rezai AR, Carpenter LL, et al. A randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression. Biol Psychiatry. 2015;78(4):240-248.