Sant Pau continues to lead in the treatment of pharmacoresistant schizophrenia with deep brain stimulation (DBS) worldwide. After performing the first intervention of this kind in 2014 and publishing a pioneering study in 2020, the hospital is now launching a second scientific study with a group of 6 new patients to analyze the long-term effects of DBS and expand therapeutic targets in the brain. This will further personalize the surgery, which is minimally invasive but extremely complex. Thus, Sant Pau is the hospital with the highest number of pharmacoresistant schizophrenia patients treated with DBS and monitored for an extended period.
“In 30% of cases, schizophrenia is resistant, and of this percentage, 60% do not respond to the last line of treatment. These patients still experience delusions and hallucinations… they are very isolated individuals with many health problems, at a higher risk of drug or alcohol consumption, and suicide… often precisely to alleviate these symptoms,” explains the principal investigator of the study, Dr. Iluminada Corripio, from the Neurological Diseases, Neuroscience, and Mental Health Group at the Sant Pau Research Institute and director of the Psychiatry and Mental Health Service at the Vic Hospital Consortium.
She adds, “Having reached the end of the road in terms of pharmacological treatment, we have decided to apply DBS in these patients, where we have all the experience of the Neurosurgery team, which has already successfully applied it in Parkinson’s, major depression, Huntington’s disease, and also in schizophrenia, publishing in 2020 the results of the first study carried out in the world in this field.”
The first pilot study was conducted on 8 patients with pharmacoresistant schizophrenia to evaluate the clinical response of DBS. According to the results, clinical improvement occurred in half of the patients, and in 2 of them, delusions and auditory hallucinations practically disappeared. According to Dr. Corripio, “the new study is a natural continuation of this first project but incorporates all the scientific improvements in terms of technique, knowledge of the pathology… and also in personalization, carefully choosing the location of the electrodes.”
A key innovation in this new study is the increase in the number of therapeutic targets in each patient. Dr. Rodrigo Rodríguez, coordinator of the Functional Neurosurgery Unit and deputy of the Neurosurgery Service at Sant Pau, explains that “we have tried to further personalize the treatment, using longer electrodes than usual with the ability to include two different therapeutic targets in their trajectory, meaning they can act on two different brain networks of the limbic system, which controls the behavior of these patients. If one therapeutic target is not sufficiently effective, we can use the other and improve the results for the patient. We can stimulate each target independently or stimulate both simultaneously depending on each patient’s case.”
The intervention is very minimally invasive but involves highly complex surgery from a technological perspective. “The precision in placing the electrodes must be millimetric,” says Dr. Rodríguez, “and requires a detailed and precise preoperative neuroimaging study to determine the cerebral coordinates, the area of the brain network that the electrodes will stimulate, where the multidisciplinary work between psychiatrists and neurosurgeons is fundamental.”
During the intervention, data from the preoperative neuroimaging study, from the magnetic resonance imaging, is transferred to the neuronavigator and merged with an intraoperative CT scan that allows for this millimetric precision in placing the electrodes “using very sophisticated and advanced software.” The surgery, very minimally invasive, involves “making two perforations in the skull to place DBS electrodes that will regulate and neuromodulate the disorder caused by the patient’s motor dysfunction.” Subsequently, the electrodes are connected to small cables that run under the skin and reach a neurostimulator—similar to a small pacemaker—placed in the patient’s chest or abdomen.
This neurostimulator generates electrical impulses or stimulation waves that can be adjusted with an external remote control to observe the desired response. “We can control the intensity of the electrical current—i.e., the amperage—the waveform—which is like the beat produced by the electrode—and the stimulation frequency. This allows us to produce a change in neuronal response in the area that then interacts with the rest of the limbic system circuit.” Dr. Rodríguez notes that “we typically use high frequencies that produce an electrical block of the area, meaning the neuronal transmission in the area.”
Neuromodulation of brain networks with DBS is not immediate. Dr. Rodríguez explains that “the brain operates with electrical discharges, and interaction with the electrodes—with specific frequencies and intensities—can produce stimulation or inhibition of neuronal activity.” DBS in schizophrenia works as an inhibitor, “reducing the activity of that specific brain network, and this interacts with the rest of the brain circuits. As a result, neuromodulation normalizes the structures of the limbic system, and over time, regulates the disease.”
Dr. Alexandra Roldán, from the Psychiatry Service at Sant Pau, who conducted her doctoral thesis with the results of the first project, emphasizes that “based on our previous experience, a minimum of 6 months is needed to see if there is any type of response in patients. We have even seen how patients from the first pilot study who initially did not respond to DBS did so after a year, a year and a half, or even two years because the restructuring of brain circuits is not automatic, does not happen overnight, and requires time.”
Especially during the initial post-intervention stage, close monitoring of patients undergoing DBS is necessary, requiring a comprehensive intervention plan: pharmacological, psychotherapeutic, and rehabilitative in response to the improvement of schizophrenia symptoms.
“These patients need to readjust to daily life, family, and social environment. We provide psychological therapy focused on their social recovery,” explains Dr. Roldán. “They are individuals who have often been isolated at home because they are afraid to go out, feel threatened, and have no social interaction. Sometimes, they even have such severe symptoms that they are institutionalized. And we must carry out individual recovery because despite the significant improvement obtained with DBS, they cannot automatically return to normal life.”
Sant Pau Hospital has been using DBS for 25 years. Initially, in patients with Parkinson’s disease, but currently also in other pathologies such as cluster headache or suicide headache, Huntington’s disease, and major depression.
In October 2022, it applied DBS for the first time in Huntington’s disease, a hereditary, rare, and neurodegenerative neurological disorder where one of the main symptoms is chorea, continuous and uncontrolled movements in various parts of the body (St. Vitus dance). Worldwide, fewer than a hundred patients with this disease have undergone this technique, consolidating the leadership of the Movement Disorders Unit of the Neurology Service at Sant Pau and the Neurosurgery Service in this field.
In 2023, the Mental Health Research Group of the Sant Pau Research Institute published a study in The Journal of Clinical Psychiatry that included the longest follow-up of patients carried out in Europe (for 11 years, from January 2008 to June 2019) in 16 patients with major depression resistant to conventional treatments. The results concluded that DBS of the subcallosal cingulate gyrus can offer significant and lasting benefits to the majority of the studied patients: 75% responded to treatment, and 50% achieved remission, meaning a reduction of symptoms below the threshold considered pathological.
