Emily Hollenbeck lived with a deep, recurring depression She compared her to a black hole where gravity felt so strong and her limbs were so heavy that she could barely move. She knew the disease could kill her. Both parents had committed suicide.
She was willing to try something extreme: having electrodes implanted in her brain as part of an experimental therapy.
Researchers say the treatment – called Deep brain stimulation, or DBS — could ultimately help many of the nearly 3 million Americans like her who suffer from depression and resist other treatments. It is approved for conditions such as Parkinson's disease and epilepsy, and many doctors and patients hope it becomes more widely available depression soon.
The treatment gives patients targeted electrical impulses, similar to a pacemaker for the brain. A growing body of current research is promising, and more is underway—though two large studies that showed no benefit from using DBS for depression temporarily halted progress and some scientists continue to raise concerns.
Meanwhile, the Food and Drug Administration has agreed to expedite its review of Abbott Laboratories' application to use its DBS devices to treat treatment-resistant depression.
“At first I was overwhelmed because the concept seemed so intense. It's like brain surgery, so to speak. There are wires embedded in your brain,” said Hollenbeck, who is involved in ongoing research at Mount Sinai West. “But I also felt at that point that I had tried everything and was desperate for an answer.”
“Nothing else worked”
Hollenbeck suffered from symptoms of depression as a child and grew up in poverty and occasional homelessness. But her first major seizure occurred in college, after her father's suicide in 2009. Another stroke during a Teach for America trip left her nearly immobile and fearful she would lose her job at school and back in poverty decrease. She ended up in the hospital.
“I ended up having kind of a switching pattern,” she said. After responding to medication for a while, she relapsed.
She managed to obtain a doctorate in psychology despite losing her mother in the final year of her studies. But the black hole kept returning to pull them in. Sometimes, she said, she thought about ending her life.
She said she had exhausted all options, including electroconvulsive therapy, when a doctor told her about DBS three years ago.
“Nothing else worked,” she said.
She was one of only a few hundred treated with DBS for depression.
Hollenbeck underwent the brain surgery while he was sedated but awake. Dr. Brian Kopell, who directs the Center for Neuromodulation at Mount Sinai, placed thin metal electrodes in a region of her brain called the subcallosal cingulate cortex, which regulates emotional behavior and is involved in feelings of sadness.
The electrodes are connected via an internal wire to a device placed under the skin in your chest that controls the strength of the electrical stimulation and delivers constant low-voltage pulses. Hollenbeck calls it “continuous Prozac.”
Doctors say the stimulation helps because electricity speaks the language of the brain. Neurons communicate using electrical and chemical signals.
In the normal brain, Kopell says, electrical activity reverberates unhindered in all areas, in a kind of dance. When depressed, dancers become stuck in the brain's emotional circuitry. DBS appears to “unlock the circuitry,” he said, allowing the brain to do what it normally would.
Hollenbeck said the effect was almost immediate.
“On the first day after surgery, she felt the negative mood and heaviness subside,” said her psychiatrist, Dr. Martijn Figee. “I remember her telling me that for the first time in years she was able to enjoy Vietnamese takeout and really taste the food. She began decorating her home, which had been completely empty since she moved to New York.”
For Hollenbeck, the most profound change was finding joy in music again.
“When I was depressed, I couldn't listen to music. It sounded and felt like I was listening to radio static,” she said. “Then one sunny summer day I was walking down the street and heard a song. I just felt this boost, this 'Oh, I want to run more, I want to walk and do things!' And I realized that I was doing better.”
She just wishes the therapy had been there for her parents.
The history of the treatment
The path to this treatment goes back two decades, when neurologist Dr. Helen Mayberg led promising early research.
But setbacks followed. Large trials started more than a dozen years ago showed no significant difference in response rates between treated and untreated groups. Dr. Katherine Scangos, a psychiatrist at the University of California, San Francisco, who also researches DBS and depression, cites several reasons: The treatment was not personalized and researchers examined the results over several weeks.
Some later research showed that depression patients experienced stable, long-term relief from DBS for years. Overall, DBS for depression is associated with an average response rate of 60% across different brain targets, one Study 2022 said.
Treatments tested by different teams are now much more tailored to the individual. The Mount Sinai team is one of the most prominent DBS depression research teams in the United States. There, a neuroimaging expert uses brain images to pinpoint the exact spot where Kopell should place the electrodes.
“We have a template, a blueprint for exactly where we’re going to go,” said Mayberg, a pioneer in DBS research and founding director of the Nash Family Center for Advanced Circuit Therapeutics at Mount Sinai. “Every brain is a little different, just like a person’s eyes are a little further apart or their nose is a little bigger or smaller.”
Other research teams also tailor treatment to individual patients, although their methods are slightly different. Scangos and her colleagues study different targets in the brain and deliver stimulation only when needed for severe symptoms. She said the best therapy may be a combination of approaches.
As teams continue to work, Abbott is launching a large clinical trial this year ahead of a possible FDA decision.
“The field is progressing pretty quickly,” Scangos said. “I hope we will receive approval shortly.”
However, some doctors are skeptical, citing possible complications such as bleeding, stroke or infection after surgery.
Dr. Stanley Caroff, a professor emeritus of psychiatry at the University of Pennsylvania, said scientists still don't know the exact pathways or mechanisms in the brain that cause depression, making it difficult to choose a location for stimulation. It's also difficult to select the right patients for DBS, he said, and approved, successful treatments for depression are available.
“I don’t think there’s any scientific evidence from a psychiatric perspective,” he said of DBS for depression.
Go forward
Hollenbeck acknowledges that DBS was not a panacea; She still takes medication for depression and requires ongoing care.
She recently visited Mayberg in her office and discussed recovery. “It’s not about being happy all the time,” the doctor told her. “It’s about making progress.”
That's what researchers are currently studying – how to track progress.
Current research by Mayberg and others in the magazine Nature has shown that it is possible to see how someone is feeling at any time. When analyzing the brain activity of DBS patients, researchers found a unique pattern that reflects the recovery process. This allows them to objectively observe how people are feeling better and distinguish between impending depression and typical mood swings.
Scientists confirm these results with newer DBS devices in a group of patients that includes Hollenbeck.
You and other participants do most of their work at home. She regularly conducts brain recordings for researchers by logging on to a tablet, placing a remote control over the pacemaker-like device in her chest and sending the data. She answers questions that arise about her feelings. She then records a video that is analyzed for facial expression and language, for example.
Occasionally she goes to Mount Sinai's “Q-Lab,” an immersive environment where scientists conduct quantitative research and collect all sorts of data, including how she moves in a virtual forest or makes circles in the air with her arms . Like many other patients, she moves her arms more quickly now that she is feeling better.
Data from recordings and visits are combined with other information, such as life events, to record how she is doing. This helps doctors make decisions such as whether to increase their current dose – which they once did.
One morning, Hollenbeck removed her collar and brushed her hair aside to reveal scars on her chest and head from her DBS surgery. For her, they are signs of how far she has come.
She makes her way around the city, taking walks in the park and visiting libraries, which were a refuge in her childhood. She no longer fears that normal life challenges will trigger severe depression.
“The stress is pretty extreme at times, but I can see and remember, even on a physical level, that I'm going to be OK,” she said.
“If I hadn’t had DBS I’m pretty sure I wouldn’t be alive today.”
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