The INTREPID study group, a team of 49 researchers from 30 academic and medical institutions, reports on sustained five-year benefits from subthalamic nucleus deep brain stimulation for Parkinson’s disease. They find improved motor function and daily living activities with a 28% reduction in anti-Parkinson’s medication.
Parkinson’s disease limits movement, independence, and quality of life. Previous studies have examined deep brain stimulation as a therapy for motor symptoms with positive patient-reported outcomes in moderate to severe disease.
In the study, “Five-Year Outcomes from Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson Disease,” published in JAMA Neurology, researchers conducted a prospective, randomized (3:1), 12-week double-blind, sham-controlled trial with a five-year open-label follow-up to evaluate long-term outcomes and safety of subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson disease.
Across 23 US movement disorder centers, 191 patients were implanted and randomized during the 12-week blinded phase, and 137 completed five-year follow-up, representing 72%. Mean age at consent was 60 years, with 73% male.
Intervention involved bilateral STN-DBS using a constant current system. Randomization occurred in a 3:1 ratio to active vs. subtherapeutic settings for 12 weeks, and sessions were performed with and without medication. Unified Parkinson’s Disease Rating Scale (UPDRS) served as a core assessment.
Motor function in the medication-off, stimulation-on condition improved from a mean UPDRS-III of 42.8 to 21.1 at year one, a 51% change, and to 27.6 at year five, a 36% change. Year one brought a 41% improvement in activities of daily living in the medication-off state from 20.6 to 12.4, with a 22% improvement at year five to 16.4.
Dyskinesia scores fell from 4.0 to 1.0 at year one, 75%, and to 1.2 at year five, 70%. Levodopa equivalent daily dose decreased by 28% at year one and remained at 28% at year five.
UPDRS-III motor examination subcategories in the medication-off, stimulation-on condition showed sustained gains for rest tremor and postural or action tremor at 81% and 67%, respectively, in year one and 76% and 65% at year five. Rigidity improved 60% at year one and 47% at year five. Bradykinesia improved 42% at year one and 25% at year five. Gait improved 45% at year one and 11% at year five.
In the medication-on, stimulation-on condition, UPDRS-III (motor exam) improved 18% at year one and worsened by 12% at year five, with rest tremor, postural or action tremor, and rigidity improved at both time points and no improvements for bradykinesia or gait.
UPDRS-IV (complications from treatment) improved 56% at year one and 47% at year five. UPDRS-I (cognitive function, mood, behavior) showed minimal change at year one (P = .63) and worsened by 67% at year five. UPDRS-II (daily living tasks) showed virtually no change at year one (P = .97) and worsened by 70% at year five.
Patient satisfaction averaged 94% across five years. Survey responses indicated perceived improvement by participants at a mean 87%, physicians at 93%, and caregivers at 82%, with 80% to 88% maintained across the period.
Infection was the most frequent device or procedure-related serious adverse event in nine participants, eight requiring surgery. Additional serious events included one suicide attempt attributed to the implant procedure and stimulation, two cerebral hemorrhages with neurological sequelae, and four seizures. Ten deaths were reported with causes that included PD, cardiac events, physical trauma injury, hypoxia, failure to thrive, and cerebral hemorrhage, with none related to the study.
Authors conclude that subthalamic nucleus deep brain stimulation sustained meaningful motor gains through five years with some attenuation over time. STN-DBS reduced anti-parkinsonian medication use and dyskinesia and improved activities of daily living, with short-term quality-of-life gains that lessened by year five.
Across five years, treatment effects persisted in the context of progressive disease. Reported deaths were not study related, and infections were the most frequent device or procedure-related serious adverse event.
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More information:
Philip A. Starr et al, Five-Year Outcomes from Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson Disease, JAMA Neurology (2025). DOI: 10.1001/jamaneurol.2025.3373
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