Researchers at UCSF believed that a more personalized, deep brain stimulation could be a key. While DBS isn’t new, the UCSF team’s approach in their recently released study was unique.
With 250 million people worldwide suffering from depression, the global drug market was valued at $18.9 billion in 2019 and projected for growth. Yet 10-20% of those suffering from depression don’t get help from current treatments.
Researchers at the University of California, San Francisco (UCSF) believed that more personalized, deep brain stimulation (DBS) could be a key. While DBS isn’t new, the UCSF team’s approach in their recently released study was unique.
Patient one, Sarah, was diagnosed with childhood onset, severe and treatment-resistant major depressive disorder. Years of medications and even ECT therapy had not helped her condition. The past five years had been the darkest she’d ever experienced.
Desperate for help, she signed up for the UCSF clinical trial. Sarah would be the first person ever to attempt to treat depression with electrodes implanted in her brain, sending quick energy bursts as circuitry changes were detected.
Deep brain stimulation had been tried before for depression, but the stimulator constantly worked and without an individually targeted location. With implanted SEEG electrodes, the team identified the biomarker of Sarah’s MDD symptoms through a 10-day period of mapping her intracranial corticolimbic circuitry mapping.
For the treatments, the NeuroPace RNS system would be utilized, a device already approved by the FDA for epilepsy treatments. Once in place, closed-loop stimulation is automatically administered when the patient’s own physiological activity indicates the need for a pulse.
When Sarah went into surgery, she measured 36 out of 54 on the Montgomery–Åsberg Depression Rating Scale. At the first during-treatment assessment after just 12 days, it had already dropped to a 14. Several months later, Sarah’s MADRS score was below 10, which is considered remission from her severe depression. The up-to 300 per-day, 6-second bursts of electricity have changed her life.
Researchers wrote, “Both the rapidity and intensity of this clinical response was highly unusual in treatment-resistant depression, where the 1-year remission rate for ‘treatment as usual’ is approximately 3.5% and symptom relief from DBS can take months to emerge.”
Experts in the field are enthusiastic about these results but also cautious.
“It’s only one patient, so we have to be careful,” Andres Lozano, professor of neurosurgery at the University of Toronto, said.
“But if it translates to other patients and if the results are longstanding and enduring then it’s very exciting.”
The UCSF team is anxious to see if these results can be duplicated. Two other patients have been enrolled, with hopes to add up to nine more eventually.
While this approach is far too complex and time-consuming for the millions suffering from depression if proven successful with more patients, it could suggest a new way to address one of the most difficult-to-treat mental illnesses.
Katherine Scangos, who helped lead the research team, hopes that a better understanding of these brain circuits could lead to paths of better modulation. Paths that wouldn’t require brain surgery, thus making it more accessible to the masses.
For Sarah, when the stimulator was turned on, she “felt the most intensely joyous sensation.” She laughed out loud, something that hadn’t happened in years, and smiled a real, genuine smile.
It’s been over a year since the device was turned on for Sarah. Her worldview gradually lightened, and the suicidal thoughts disappeared within a few weeks.
While the device is calibrated so Sarah can’t feel the pulses it sends, she feels a heightened sense of alertness, energy and positivity within about 15-20 minutes of when she believes it has been activated.
Sarah’s neurosurgeon, Edward Chang, was the pioneer thinker on this project. He believes brain stimulation, used in coordination with therapy and medication, could be a key treatment option for those who can’t find relief with therapy and medication alone.
“We’re at the very beginning of figuring out how this works,” Chang said. “We have a lot to learn.”
Chang customized the $30,000 worth of devices the team implanted to work the way he wanted it to. While the hope is to identify and treat the patient’s key circuits without surgery, for now, it is a “more precise and targeted with more control and fewer side effects.”
The research paper concluded with the belief that this result can be duplicated to treat others with severe, uncontrolled major depressive disorder.
“In line with our model, this patient’s depression acutely improved once closed-loop therapy was initiated and the effect has been maintained with sustained closed-loop therapy through the time of writing this article.”
About 7% of the adult population currently suffers from a major depressive disorder.
