Brain stimulation acts ‘like a switch’ to turn off severe depression for one patient
From John Lok/UCSF

Brain stimulation acts ‘like a switch’ to turn off severe depression for one patient

After years of suffering, a patient with severe and untreatable depression has finally found relief with an experimental brain implant originally developed to help people with epilepsy, researchers in California reported Monday.

It’s only a single patient, but the team at the University of California San Francisco says it has seen remarkable results with the device, which is calibrated to detect the signals associated with depressive symptoms in the patient’s brain, and interfere with them.

“When we turned this treatment on, our patient’s depression symptoms dissolved and in a remarkably small time she went into remission,” Dr. Katherine Scangos, a psychiatrist and neuroscience specialist at UCSF who led the study team, told reporters.

“It was like a switch.”

One year later the patient, who is identified only as Sarah, says the device has banished her depression with no side-effects.

“I had exhausted all possible treatment options with no success at lifting the depression that had descended five years earlier,” Sarah told reporters.

“My daily life had become so restricted and impoverished by depression that I felt tortured by each day and forced myself to resist the suicidal impulses that overtook me several times an hour. When I first received stimulation, I felt the most intensely joyous sensation,” she added.

“And my depression was a distant nightmare for a moment.”

The study team worked intensely with Sarah to first map the areas of her brain that became active when she was experiencing the worst symptoms of depression. They implanted two small wires into her brain to detect the associated brain activity and then deliver a pulse of electricity that interrupts the signal.

It’s a highly personalized treatment and one that will require years more of research to develop into anything that will be useful to the wider public, the team reported in the journal Nature Medicine.

But it provides some small hope for people with the most severe and intractable forms of depression, who are not helped by cognitive therapy, drugs or even electroconvulsive shock therapy, the team said.

“To identify a patient’s unique depression circuit we placed temporary electrodes, which are really thin wires, into mood-related brain regions in patients with depression. And then we delivered small pulses of stimulation across the regions, one by one, and recorded the patient’s clinical response,” Scangos said.

Other researchers have tried this approach for depression. According to the US National Institute of Mental Health, a review of various deep brain stimulation techniques shows that 40% to 50% of people treated with deep brain stimulation show more than 50% improvement. A different type of stimulation called vagus nerve stimulation is also being tested, as well as several techniques using magnetic stimulation of parts of the brain.

Precision mapping

But Scangos and her colleagues said the difference on their approach was the careful mapping of Sarah’s particular brain activity and the calibration of the device to respond to changes in signaling.

“There is not one depression area or one mood area in the brain,” said UCSF neurosurgeon Dr. Edward Chang, who was a member of the study team.

In Sarah’s case, signals from the amygdala, a small structure in the brain associated with emotions, predicted her worst symptoms. Chang and colleagues adapted a commercially available device approved by the US Food and Drug Administration for treating severe epilepsy.

“It affords us precision in a way that we never had before in treating depression. This is our first demonstration of personalizing,” Chang said.

“The exact mechanism of how it treats the symptoms is unclear,” he added. The team got the idea when they saw evidence that people being treated for epilepsy with the device often reported their symptoms of depression were improved by its use.

“The is not a demonstration of the efficacy of this approach. We have a lot of work ahead of us as a field to validate these results, to see if this is something that will be enduring as a treatment option,” Chang said.

Sarah has the device permanently implanted now. A small piece of her skull was removed to accommodate the device, which is about the size of a matchbook, Chang said.

Scangos said Sarah receives about 30 minutes of stimulation on and off in a day to control her symptoms. The battery in the device should last about 10 years at this rate of use, she said. “We titrated the stimulation so she cannot detect it,” Scangos said,

Such an approach is only for the most severe cases, Scangos and Chang said.

“We didn’t know if we were going to be able to treat her depression at all because it was so severe,” Scangos said.

“Even though this is what we call minimally invasive, it is surgery and it does have risks,” Chang added.

‘This joyous feeling washed over me’

For Sarah, the effects were worth the risks. “Any kind of release would have been better than what I was experiencing,” she said. “Depression controlled my life. I barely moved. I barely did anything.”

The first time the team tried the stimulation after mapping her brain, “I just laughed out loud,” Sarah said.

“It was the first time I had spontaneously laughed and smiled where it wasn’t faked, it wasn’t forced, for five years,” she added. “This joyous feeling washed over me.”

It took considerable adjustment to make the stimulation feel seamless — and to make sure the effects lasted for longer than a few minutes.

“At first, within a few weeks, the suicidal thoughts just disappeared. Then it was just a gradual process. It was like my lens on the world changed,” Sarah said.

“Everything has gotten easier and easier and easier.”

One day sticks in her mind. “I just remember coming home one of the first times the device was on. I could see the bay and where it met the marshes, and I remember being, god — like, the color differentiation. It’s gorgeous — the light.” Sarah’s depression symptoms had made the world seem gray and uninteresting.

Not a moral failing

“By the end of this, I said oh my god — this is no different from someone with Parkinson’s,” Sarah said.

“Nobody says to somebody with Parkinson’s ‘if you just have a positive attitude and bear up, you’ll cure yourself.’ No one says this to someone with cancer,’ ” she added. But people do not treat depression as a disease, she said.

“The feedback we get from society is it is a moral failing. It must be something that you are doing wrong,” she said. “Even if it is well meaning.”

Every failed treatment made her feel more like a failure, Sarah said. “The stigma of depression is an overwhelming weight,” she said.

According to NIMH, depression is characterized by a persistent feeling of emptiness and guilt, loss of hope and energy and other symptoms. “Depression is one of the most common mental disorders in the U.S. Current research suggests that depression is caused by a combination of genetic, biological, environmental, and psychological factors,” NIMH says.

About 5% of people worldwide suffer from depression, according to the World Health Organization.

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