The largest long-term study of subthalamic deep brain stimulation (DBS) for Parkinson's disease has demonstrated sustained clinical benefits over five years, providing compelling evidence for the therapy's durability in treating moderate to advanced disease stages. The INTREPID trial, published in JAMA Neurology, tracked outcomes in 313 patients implanted with Boston Scientific's Vercise DBS system between 2013 and 2022.
Sustained Motor Improvements Over Five Years
Of the 191 patients who received DBS, 137 completed the five-year follow-up period. The results showed remarkable and sustained improvements in motor function as measured by the Unified Parkinson's Disease Rating Scale (UPDRS-III). At baseline, participants had significant motor impairment with average UPDRS-III scores of 42.8 in the "off medication" state.
By year one, DBS reduced this score to 21.1, representing a 51% improvement. While some decline occurred by year five, the benefit remained clinically meaningful with a 36% overall improvement compared to pre-surgery levels. This sustained benefit occurred despite the progressive nature of Parkinson's disease.
Dramatic Reduction in Dyskinesia
The study revealed particularly striking results for dyskinesia, a disabling side effect of long-term medication use. Dyskinesia scores dropped from 4.0 at baseline to 1.0 at year one and stabilized at 1.2 after five years, reflecting a 70-75% reduction that was maintained throughout the study period.
Patients also experienced improvements in their ability to manage day-to-day tasks, with baseline scores of 20.6 showing a 41% improvement in year one that leveled to a still-significant 22% gain by year five.
Reduced Medication Dependence
A key finding was the sustained reduction in medication requirements. Patients reduced their levodopa equivalent doses by 28% in the first year, with this reduction maintained through the five-year mark. This highlights DBS's potential to not only improve symptoms but also lower dependence on medications that carry significant side effects.
Safety Profile and Clinical Implications
The most frequent serious adverse event was infection, reported in nine participants. Ten deaths occurred during the study, though none were related to DBS or the trial itself. These safety findings are consistent with previous DBS studies and support the therapy's acceptable risk-benefit profile.
"For the first time, we can clearly see that the benefits of DBS, improvements in motor symptoms, reduced medication needs and better quality of life are sustained at five years," said Dr. Adolfo Ramirez-Zamora, division chief of movement disorders at the Norman Fixel Institute for Neurological Diseases at University of Florida Health.
Shifting Treatment Paradigm
The findings support a shift in how DBS is positioned in Parkinson's treatment algorithms. "DBS used to be seen as a last resort, but we now know it provides the most sustained benefit when offered in the moderate stages of Parkinson's disease, when motor complications are the main source of disability," Ramirez-Zamora explained.
The study involved nearly 200 patients at 23 movement disorder centers who received DBS implants in their subthalamic nucleus, a brain structure crucial for motor control. Patients were randomly assigned to either receive immediate stimulation or wait 12 weeks before device activation.
Future Directions
Co-researcher Dr. Michael Okun, director of the Fixel Institute, emphasized the implications for future DBS development. "The future of DBS will be about smarter devices, more personalized programming and broader access. Studies like this one not only prove the therapy's durability but also set the stage for the next generation of technologies to improve patients' lives."
The INTREPID results reinforce DBS as a standard treatment option for patients with moderate to advanced Parkinson's disease, particularly those struggling with medication fluctuations and uncontrolled motor symptoms. The sustained benefits over five years provide strong evidence for the therapy's long-term value in managing this progressive neurological condition.
