As Abbott studies DBS for depression, what might be next?

Abbott Neuromodulation Global Clinical & Regulatory Divisional VP Jenn Wong discusses the TRANSCEND trial, imaging tech advancing deep brain stimulation, and other potential applications of DBS.

Abbott is studying deep brain stimulation (DBS) as a potential treatment for depression, taking the technology in a direction that could advance other mental health therapies.

Abbott received FDA Breakthrough Device Designation for DBS in 2022 to investigate the technology’s potential for treating treatment-resistant depression, a diagnosis for people with a major depressive disorder who have unsuccessfully tried multiple treatments.

The first patient in Abbott’s TRANSCEND (Treatment Resistant Depression Subcallosal Cingulate Network DBS) study recently had an Abbott Infinity DBS system implanted in them.

DBS systems send electricity from a chest implant through tiny leads that run up a patient’s neck and into their brain. DBS systems are already approved by the FDA for treating epilepsy and movement disorders like Parkinson’s and essential tremor.

“A deep brain stimulator is like a pacemaker for the brain. It’s sending electrical pulses that are meant to disrupt the electrical activity,” Abbott Neuromodulation Global Clinical & Regulatory Divisional VP Jenn Wong said in an interview.

“The area that we’re targeting is thought to be involved in depression,” she continued. “… Depression represents a change for us from movement disorders into a more psychiatric space.”

As researchers home in on the exact part of a patient’s brain where stimulation could treat depression, a key technology unlocking this approach is modern tractography,  imaging that models nerve tracts in three dimensions to help neurosurgeons place brain implants.

“The most important part of neuromodulation is the right patient and the right target,” Wong said.

Magnetic resonance imaging (MRI) and CT scans are used before and during the implantation procedure for accurate and precise placement of the leads in the brain.

“Whether you’re going to have a good therapeutic effect depends on how close you are to the area that you’re stimulating, so that imaging process is very important,” Wong said. “…. There are patient-specific considerations for the way  they access the tract. That’s where the tractography comes in, because you have to be aware of the vasculature within the brain to be accurate.”

Abbott’s TRANSCEND study design

Patient selection is critical to find those that are likely to benefit from DBS, Wong said. That’s one factor that may be responsible for the failure of previous studies into DBS for depression.

Abbott is only opening the TRANSCEND study to patients who have failed at least four different depression treatment approaches, but is aiming for a broad spectrum of patients.

“Because depression can affect anyone at any point in their lives, we want to make sure our enrollment is reflective of the U.S. adult population and includes a balanced representation of men and women across the nation with diverse backgrounds,” Wong said.

Another potential factor for the failure of previous trials is that they may not have been long enough. Abbott’s multi-center TRANSCEND trial will evaluate DBS therapy for patients with over 36 months.

Patients “need to be able to agree to and maintain a fairly regimented schedule for check-ins with the trial team,” Wong said. “We want to monitor and track progression on a regular basis over the course of three years, which is a significant commitment for most people to make.”

All of the patients in the study will have the Infinity DBS system implanted, but some will not receive any stimulation therapy for the first 12 months. After the first year, all patients will have their devices activated. That’s one reason the randomized, double-blind trial uses Abbott’s non-rechargeable Infinity DBS system rather than the rechargeable Liberta RC DBS system.

“An important aspect is making sure the patients don’t know if the stimulation is on or off, and if we had a rechargeable, that would be a little bit more challenging to manage,” Wong explained.

Researchers at the Icahn School of Medicine at Mount Sinai placed the first implant for the TRANSCEND trial.

Mount Sinai’s Nash Family Center for Advanced Circuit Therapeutics Founder Dr. Helen Mayberg pioneered the science behind DBS for treatment-resistant depression, Mount Sinai said in a news release announcing that first implantation. 

“She is credited with identifying the subcallosal cingulate as a signaling hub for depression in the brain and discovering that modulation of this brain area can help alleviate depression symptoms,” Mount Sinai said. “Previous research, much of it pioneered by Dr. Mayberg through independent, single-arm, open-label, grant-funded studies at several leading academic research institutions and for the past seven years at Mount Sinai, has shown sustained improvement in symptoms of depression.”

What might be next for DBS?

If the TRANSCEND study is successful and the therapy passes regulatory review, doctors will have a new option for treating some of the toughest depression cases.

“For physicians, the most important thing is for them to have the range in their toolbox to work with those patients, especially because not only are there compliance concerns with drugs, there are also side effects for those drugs, especially over the long term,” Wong said. “Patient tolerance of different side effects may drive a preference for more surgical options.”

The factors that make DBS appealing for treating depression extend to other potential applications.

“The thing about DBS is because it is something that’s permanently implanted, it’s well suited for these chronic diseases where people have a lot of suffering over time,” Wong said. “That’s something that we also noticed about depression and why we’re focused on treatment-resistant depression — also called difficult-to-treat depression — because these patients spend a lot of time trying other therapies that tend to have more of an acute effect.”

“That’s the way that I would look at different patient populations that are eligible for DBS in the future,” she continued. “Which patients spend a long time focusing on their disease and the symptoms over their lifetime, and is that an opportunity for DBS to make a difference?”

Wong said she and her team are monitoring other studies into chronic pain and anxiety-driven disorders like obsessive-compulsive disorder.

With researchers learning more about the different targets in the brain and the needs of patients, she said, “the door is open.”