Deep brain stimulation which relies on electrical pulses is showing positive signs in the fight against depression.
Image: Supplied
Katherine Ellison
Brandy Ellis calls herself a cyborg.
Two small electrodes - thin metal wires - implanted deep inside her brain lead under her skin to a battery pack in her chest. Pulsing about 130 times a second, the deep brain stimulation (DBS) device, a kind of pacemaker, energizes an area that scientists say is key in regulating moods.
Ellis, 49, a regulatory compliance consultant for a corporate insurance firm in Boynton Beach, Florida, says the device is taming her previously intractable depression. The disorder had previously “made everything feel like sandpaper,” she says, leaving her unable to work or even to sleep, with her brain “screaming at me that this is too hard, you can’t do this.”
She’s feeling a lot better today, she says, adding: “These electrodes are now pretty core to my existence.”
DBS is one of several emerging, high-tech therapeutic approaches - a.k.a. electroceuticals - that proponents say are extending psychiatry’s ability to help millions of patients. Increasingly over the past 20 years, testimonials to the potential of treatments that modulate brain functioning, such as DBS, transcranial magnetic stimulation, vagus nerve stimulation and, most recently, focused ultrasound, have been fueling new hope, despite considerable expense and hardship for patients, and mixed evidence of their effectiveness.
Emory University neurologist and psychiatrist Patricio Riva Posse, one of Ellis’s therapists, describes the new trends - combined with ever more sophisticated brain-scanning technologies and new optimism about psychedelic drugs such as ketamine and psilocybin - as explosive progress.
“Up until about a decade ago, we were very much still into asking: What is the best antidepressant? Is there a better version of Prozac or Lexapro?” he says. “But suddenly now, from all different areas, there are all these new treatments and technologies.”
New treatments can’t come too soon for millions suffering from severe mental illnesses, including major depressive disorder and obsessive-compulsive disorder (OCD), yet who haven’t been helped by standard therapies.
Reports vary widely, but as many as 30 percent of people with major depressive disorder - an estimated 9 million U.S. adults take medication for the condition - and up to 60 percent of Americans with OCD are considered “treatment-resistant.” The National Institute of Mental Health estimates that 1.2 percent of U.S. adults have OCD, which would amount to some 3.1 million people.
Since the late 1930s, electroconvulsive therapy (ECT) - “shock treatments” that induce seizures, under general anesthesia - has been the gold-standard neuromodulatory approach to stubborn depression, with high rates of positive response. Yale Medicine estimates that ECT is effective for about 60 percent of patients.
But some patients aren’t helped; many relapse, and more sophisticated knowledge of the brain has led to a quest for more targeted and enduring strategies. Public opinion of ECT also plummeted following negative portrayals in books and movies such as “One Flew Over the Cuckoo’s Nest.”
Many electroceuticals have longer and more impressive track records - and more clearances from the Food and Drug Administration - for treating movement disorders such as Parkinson’s disease than they do for psychiatric illnesses. But some experts argue that the underlying dynamics of failures of mobility and emotional stability may be more similar than once supposed.
“Your brain isn’t just a big bag of chemicals,” says neurosurgeon Brian Kopell, director of the Center for Neuromodulation at the Mount Sinai Health System in New York City and head of a clinical trial of DBS for depression that launched in March.
“Your brain is a very intricate symphony of different electrical circuits,” he adds. “And the idea that something like Parkinson’s and OCD or depression can have similar features and underpinnings in the brain is really exciting. It’s sort of like a grand unified theory of how the brain works and breaks down.”
To be sure, even the most hopeful advocates of the high-tech interventions concede their limitations.
“It’s not a happy switch,” says Posse, who notes that DBS and other novel therapies can’t address many of the challenges of being human, including loneliness, injustice and world-weariness.
“I still have times when I struggle with my moods,” says Ellis, who like many electroceutical patients supplements her DBS with antidepressant medication. “The difference is that my moods are appropriate to my situation. Depression isn’t a sadness; it’s an absolute inability to have an appropriate mood.”
Mount Sinai neurologist Helen Mayberg, who led a pioneering study of DBS for depression in 2005, describes the approach as “repairing a broken connection. We fix the backbone, but the patient still needs holistic care.”
Researchers have called for more investigation of DBS for major depressive disorder. While several studies suggest promise, a 2024 meta-analysis concluded that the limited data from controlled trials “do not demonstrate significant improvement over placebo.”
Research into an alternative implant strategy, vagus nerve stimulation (VNS), has similarly produced unconvincing results. Last summer, the first report from the largest study of its kind to date, a commercially sponsored, randomized clinical trial involving up to 1,000 patients with unipolar and bipolar depression, revealed a failure to achieve “statistical significance” because of a stronger-than-expected response from participants getting a placebo treatment.
As is also the case with psychedelic therapies, the newer e-treatments are only available to a tiny minority of people, including participants in clinical trials. Many insurance plans consider such strategies experimental and won’t cover them, putting them mostly out of reach.
The exception is repetitive transcranial magnetic stimulation, a procedure in which an electromagnetic coil is placed against the scalp, delivering magnetic pulses to stimulate the brain. As many as a third of patients in studies have gotten some relief from this noninvasive and less costly procedure, and insurance plans have been more willing to cover it for patients who have unsuccessfully tried standard treatments. The major downside is a need for many sessions - as many as five times a week, for four to six weeks - and a high rate of recurrence.
Jenna Krebs, 38, a Rochester, New York, resident who has suffered from crippling OCD, says she endured more than two decades of extensive therapy and medication, with six residential treatment programs, transcranial magnetic stimulation, ketamine infusions and 18 treatments of ECT before applying to be treated with deep-brain stimulation. She says she still had to fight with her insurance plan for nearly four months.
At last Krebs got her approval. Yet after she had the first of three planned surgeries, she says, her plan initially balked at paying for the other two. She received her implant last fall and says her life has changed dramatically. From being “an anxious mess,” she says she is now able to leave the house, go to the gym, make friends and feel joy.
Brain-stimulating implants have been defined as “minimally invasive,” but can include potential complications associated with any brain surgery, including infection, hemorrhage and death. A 2015 review of 49 studies of DBS for psychiatric illnesses found “long-term morbidity” in more than 16 percent of cases.
The pacemakers also need maintenance. For the first decade after receiving her implant in 2011, Ellis had to have yearly surgeries to replace her battery. Today she has a rechargeable battery that needs charging for 90 minutes every three days.
Still, such challenges tend to loom less large for someone at the end of her rope.
Embarking on what she says was a full year exclusively devoted to a clinical trial testing DBS for treatment-resistant depression at Emory University in Atlanta, far from home, Ellis recalls: “I figured even if it doesn’t work, they’re still going to learn something.”
Her family financially supported her as she received intensive therapy before and after a full-day surgery, during which she says she remained awake while her head was encased in a metal frame bolted to a table. Fourteen years later, she is so pleased with the results that she gives talks advocating DBS and consults for Motif Neurotech, which is working on a less invasive, wireless form of the treatment.
The newest electroceutical on the block is focused ultrasound, which can reach deeper into the brain than transcranial magnetic stimulation and in some cases appears to have a permanent effect.
Authors of a 2024 review of 10 pilot studies mostly focused on OCD found “promising” evidence of the treatment’s safety and efficacy.
The ultrasound, guided by MRI brain scans, can be used in two ways: to destroy brain cells - similar to a radiosurgical procedure that has been used in hard-to-treat OCD - or modulate them with acoustic energy. Since 2020, focused ultrasound has increasingly been studied for treating pain, dementia, traumatic brain injury and depression.
“The advantage of focused ultrasound in general is that it is completely noninvasive, it harnesses the power of sound to change the brain,” says Ahmed Raslan, a professor of neurological surgery at the Oregon Health & Science University, and one of the authors of the 2024 review.
Mayberg agreed that focused ultrasound could be a “game changer” for the field. “I’m super excited about it,” she says, while noting “they’re at the beginning of the road that we were on 20 years ago.”
The race is on to find ever safer and less expensive electroceuticals to treat psychiatric illnesses - even without gold-standard evidence that they work.
“Progress has not been linear, so are we on the verge of a paradigm shift?” Mayberg asked. “Maybe and maybe not, but in the meantime we have to maximize the tools we have.” | The Washington Post