For 40 years, advancing treatments for schizophrenia has been a goal for Judith Gault, PhD. Watching her father struggle with the serious mental health disorder, which can rob people of their sense of reality and severely disrupt their lives, continues to motivate her work.
Now, recent successes with deep brain stimulation (DBS) have placed that goal within reach for Gault, an associate research professor of neurosurgery at the University of Colorado Anschutz School of Medicine.
She and her team of psychiatrists and neuroscientists recently received conditional approval from the FDA under an investigational device exemption (IDE) for an early feasibility study in treatment-resistant schizophrenia (TRS) and schizoaffective disorder (SAD).
“I'm very familiar with how difficult it is for people and their families to navigate and find effective care for schizophrenia and schizoaffective disorder,” said Gault, who has since lost her dad. “Antipsychotics are amazing, and they help most people significantly. Even those refractory to antipsychotics still benefit from them. But we still have a lot of room for improvement.”
Current DBS uses:
- Parkinson’s disease (reduces stiffness, slowness, tremors)
- Essential tremor (eases shaking)
- Dystonia (relieves involuntary muscle contractions)
- Epilepsy (reduces number of seizures)
About 10-23% of patients have moderate to severe symptoms despite trying different antipsychotics including clozapine, the best antipsychotic for TRS. DBS could help alleviate some of the treatment challenges, but larger clinical trials are imperative to determine safety and effectiveness.
“We've had antipsychotics for over 70 years now,” Gault said. “And despite their availability and the fact that people are taking them, the life expectancy for people with schizophrenia is still decreased by about 17 years on average.”
Unemployment and incarceration rates of people with schizophrenia are 20 times higher than the general population, and an estimated 20% to 40% of people with the disorder will attempt suicide at least once in their lifetimes.
“We clearly are not meeting all the needs of people with schizophrenia.”
If approved, the CU Anschutz study will be led by Rachel Davis, PhD, division head of adult psychiatry, and run in conjunction with a study already underway at Johns Hopkins University. Initial results treating patients with persistent auditory hallucinations are positive, with two cases published.
“One experienced complete and sustained resolution of their auditory hallucinations, and another person had a 64% reduction in their auditory hallucinations to make them more bearable,” Gault said.
Schizophrenia symptoms may include:
- Delusions
- Hallucinations
- Paranoia
- Lack of drive
- Inability to feel joy
- Avoiding social contact
- Disorganized speech
- Catatonia
- Bizarre behavior
- Memory trouble
- Focus issues
(Note: Schizoaffective disorder can include any of the above symptoms along with mood issues, including depression and mania.)
DBS has been FDA approved for Parkinson’s and essential tremor for nearly three decades. It involves implanting a control device in the chest connected by a thin wire to electrodes placed in the brain.
Mild electrical signals are then sent to the targets, disrupting brain activity that leads to symptoms. Providers can turn the device on and off and adjust electronic pulses remotely.
“About 30% to 35% of people experience dose-dependent intolerable side effects that make them not want to take their antipsychotics,” Gault said. DBS may potentially reduce (but not eliminate) the need for drugs, with lower doses potentially leading to fewer or milder side effects.
An estimated 5% of people will have a single psychotic episode and not develop chronic schizophrenia. For the rest, the illness – which generally emerges in the late-teen or early-adult years – affects them for life.
“So you're talking about 50, 60 years of taking these medications. And these side effects may accumulate and start playing a bigger role in one’s quality of life,” Gault said.
Even among patients who take their antipsychotics regularly, 18% to 22% delveop breakthrough symptoms, with potentially life-aterning episodes.
“Some people with schizophrenia have persecutory delusions and unpleasant voices constantly saying negative things. So they might be afraid of people, afraid that somebody's out to harm them,” Gault said.
“Untreated symptoms make people vulnerable to being harmed while trying to escape their delusions and hallucinations.” People with schizophrenia have a roughly three- to 10-times increased risk of accidental injury or death.
With fewer than 20 published cases worldwide, DBS for schizophrenia remains experimental. Scientists need more clinical trials to refine specific targets and potentially expand symptom response.
General anxiety around the risks of brain surgery makes enrolling patients into DBS studies difficult. Targeting mental health disorders increases the recruitment challenge because of biases and ethical concerns that are important for providers to understand and address, Gault said.
Some of those concerns are rooted in a dark history of psychiatric care, including lobotomy. But medicine, both the technology and the understanding of mental illness, has come a long way since 1950, Gault said. “We would not be doing this if we felt that the benefits might not outweigh the risks.”
In her team’s studies on ethical issues and public perception, most people surveyed say they would want DBS if they had Parkinson’s disease, Gault said. “So then the question is, ‘Well, if it's good enough for Parkinson's disease, then might it also be good for people with schizophrenia?’”
Learn how CU Anschutz researchers are studying DBS for treatment-resistant obsessive-compulsive disorder: OCD Ruled Moksha Patel’s Life Until a Rare Surgical Procedure Changed Everything
As a high-volume DBS center, CU Anschutz researchers are leading the way in advancing the technology and routinely do DBS surgeries.
“So we have the expertise to safely do DBS,” Gault said. “And we need to build the evidence so we can advance the technology and ensure people with schizophrenia can make informed decisions when considering the procedure.”
The early feasibility studies focus on the people who will benefit most: Those who have no treatment options left and meet all the inclusion criteria. “These individuals tried numerous antipsychotics with different mechanisms, and they still had persistent auditory hallucinations and other symptoms like delusions.”
DBS is not for everyone, and it’s not a cure, she said. “But when you've tried everything, and nothing is quite fixing the symptoms, having another option is important.”
And, after searching for new therapies for over 40 years, the advanced DBS technology gives Gault renewed hope.
“It's modulating the circuitry in a different way than antipsychotics. I hope that we can learn from it, and that this will inform the development of other neuromodulation therapies including ones that are adaptive to symptoms and less invasive. I've never been this excited about being in the field.”
Photo at top: A brain scan illuminating areas targeted during a deep brain stimulation surgery for obsessive compulsive disorder at CU Anschutz.
Contact: Judith Gault, PhD, at judith.gault@cuanschutz.edu for information on volunteering for DBS for schizophrenia studies.
The research team for the early feasibility study also includes: psychiatrist Rachel Davis, MD; neurosurgeon Daniel Kramer, MD; neuroradiologist Jody Tanabe, MD; psychiatrist Elizabeth Fenstermacher, MD; clinical social worker Emily Hemendinger, MSW, LCSW; neurologist Drew Kern, MD; and neuroscientist John Thompson, PhD.
Key points:
- CU Anschutz researchers have received conditional approval from the U.S. Food and Drug Administration (FDA) to move forward with an early feasibility study on deep brain stimulation for treatment-resistant schizophrenia and schizoaffective disorder.
- An estimated 10-23% of patients do not adequately respond to available medications.
- Neurosurgeons already routinely use DBS for other treatment-refractory neurological disorders, including Parkinson’s, essential tremor and epilepsy.
- The therapy delivers electrical stimulation to targeted brain circuits through surgically implanted electrodes.