Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Nov 1;82(11):1181-1190.
doi: 10.1001/jamaneurol.2025.3373.

Five-Year Outcomes from Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson Disease

Philip A Starr  1 , Rajat S Shivacharan  2 , Edward Goldberg  2 , Alexander I Tröster  3 , Paul A House  4 , Monique L Giroux  5   6 , Adam O Hebb  7 , Donald M Whiting  8 , Timothy A Leichliter  9 , Jill L Ostrem  10 , Leo Verhagen Metman  11   12 , Sepehr Sani  13 , Jessica A Karl  11   12 , Mustafa S Siddiqui  14 , Stephen B Tatter  15 , Ihtsham Ul Haq  14   16 , Andre G Machado  17 , Michal Gostkowski  17 , Michele Tagliati  18 , Adam N Mamelak  19 , Michael S Okun  20 , Kelly D Foote  21 , Guillermo Moguel-Cobos  22 , Francisco A Ponce  23 , Rajesh Pahwa  24 , Kelly Lyons  24 , Cathrin M Buetefisch  25 , Robert E Gross  26   27 , Corneliu C Luca  28 , Jonathan R Jagid  29 , Gonzalo J Revuelta  30 , Istvan Takacs  31 , Michael H Pourfar  32 , Alon Y Mogilner  33 , Andrew P Duker  34 , George T Mandybur  35   36 , Joshua M Rosenow  37 , Cindy Zadikoff  38 , Suketu M Khandhar  39 , Mark Sedrak  40 , Fenna T Phibbs  41 , Joseph Neimat  42   43 , Jennifer Durphy  44 , Adolfo Ramirez-Zamora  44   45 , Julie G Pilitsis  46   47 , Ryan J Uitti  48 , Robert Wharen  43 , Michael C Park  49 , Jerrold L Vitek  50 ; INTREPID Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Five-Year Outcomes from Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson Disease

Philip A Starr et al. JAMA Neurol. .

Abstract

Importance: The Implantable Neurostimulator for the Treatment of Parkinson's Disease (INTREPID) trial was a randomized, double-blind, sham-controlled study of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD).

Objective: To evaluate the long-term (5-year) outcomes and safety of STN-DBS for PD.

Design, setting, and participants: This was a prospective, randomized (3:1), 12-week double-blind sham-controlled study at 23 movement disorder centers across the US with an open-label 5-year follow-up. Patients were implanted and followed up with the Vercise DBS system from May 2013 to December 2022. Eligibility required diagnosis of bilateral idiopathic PD with more than 5 years of motor symptoms, more than 6 hours per day of poor motor function, modified Hoehn and Yahr Scale scores higher than 2, Unified Parkinson's Disease Rating Scale (UPDRS-III) score of 30 or higher (medication-off state), and 33% or higher improvement in UPDRS-III medication-on score.

Intervention: Bilateral STN-DBS for moderate to advanced PD.

Main outcomes and measures: Primary outcomes included changes in UPDRS and dyskinesia scores, quality-of-life measures, and safety assessments. Exploratory analyses included medication reduction and DBS association with motor signs.

Results: A total of 313 patients were enrolled with 191 receiving the DBS system, and 137 participants (72%) completed the study. The study population had a mean (SD) age of 60 (7.9) years, with 139 (73%) male participants. Motor function without medication as measured by UPDRS-III improved from a mean (SD) of 42.8 (9.4) to 21.1 (10.6) at year 1 (51%; 95% CI, 49%-53%; P < .001) and 27.6 (11.6) at year 5 (36%; 95% CI, 33%-38%; P < .001). Activities of daily living without medication as measured by UPDRS-II improved from a mean (SD) of 20.6 (6.0) to 12.4 (6.1) at year 1 (41%; 95% CI, 38%-42%; P < .001) and 16.4 (6.5) at year 5 (22%; 95% CI, 18%-23%; P < .001). Dyskinesia scores decreased from 4.0 (5.1) to 1.0 (2.1) at year 1 (75%; 95% CI, 73%-75%; P < .001) and to 1.2 (2.1) at year 5 (70%; 95% CI, 63%-75%; P < .001). The levodopa equivalent dose was reduced by 28% at year 1, remaining stable at year 5 (28%; 95% CI, 26%-31%; P < .001). The most common serious adverse event was infection (9 participants). Ten deaths were reported, none related to the study.

Conclusions and relevance: Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant improvement in motor and activities of daily living scores, along with a stable reduction in anti-parkinsonian medication over the 5-year follow-up period.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Starr reported receiving personal fees from Boston Scientific during the conduct of the study; grants from Boston Scientific and fellowship funding from Medtronic outside the submitted work; and holding a patent relevant to deep brain stimulation. Dr Hebb reported holding a patent relevant to deep brain stimulation. Dr Leichliter reported receiving personal fees from Neurocrine and Teva outside the submitted work. Dr Ostrem reported receiving grants from Neuroderm, Clearpoint, Medtronic, Merz, Medtronic, Amneal, AbbVie, Supernus, and Acadia; personal fees from Highland Instruments, Supernus, Insightec, Larimar, Aspen, and AcureX; and serving on the advisory boards for Larimar Therapeutics, Aspen Neuroscience, and AcureX outside the submitted work. Dr Verhagen Metman reported receiving funds for contracted research from Rush University during the conduct of the study and personal fees from Abbott and Medtronic outside the submitted work. Dr Siddiqui reported receiving grants, personal fees, and nonfinancial support from Boston Scientific Neuromodulation and AbbVie during the conduct of the study; grants from Sunovion Pharma, Biogen, Theravance Biopharma, Neuropoint Alliance/Michael J Fox Foundation, Impax Lab, and Sun Pharma outside the submitted work; and personal fees from Medtronic outside the submitted work. Dr Tatter reported receiving grants from Monteris Medical, Inc and Azurity Phamaceuticals outside the submitted work and serving on the advisory board of Boston Scientific. Dr Machado reported receiving grants from Abbott and Medtronic outside the submitted work; personal fees from Abbott; and holding distribution rights from Enspire DBS and Ceraxis outside the submitted work. Dr Tagliati reported receiving grants from Abbott and Medtronic outside the submitted work; personal fees from Abbott; and personal fees from Boston Scientific outside the submitted work. Dr Pahwa reported receiving research support from Abbott, AbbVie, Acadia, Allevion, Amneal, Amylyx, Appello, ASK Bio, Biogen, BioVie, Bluerock (Bayer), CalaHealth, Cerevance, Cerevel, Convatec, EIP, Fasikl, Genentech, Global Kinetics, Inhibikase, Intra-cellular Therapies, Insightec, Jazz, Keiferx, Kyowa, Lundbeck, Merz, Mitsubishi Tanabe, Michael J Fox Foundation, Neurocrine, Neuroderm, Neuron 23, Ono, Parkinson’s Foundation, Praxis, PhotoPharmics, PSG, Regenxbio, Roche, Sage, Saluda, Scion, Sun Biopharma, Supernus, Teva, Theravance, TrueBinding, UCB, and Ventus outside the submitted work. Dr Lyons reported receiving personal fees from Fasikl, Sage, Jazz, and Parkinson's Foundation outside the submitted work. Dr Gross reported receiving personal fees from Boston Scientific during the conduct of the study; grants from Boston Scientific, Medtronic, and Abbott outside the submitted work; and personal fees from Boston Scientific, Medtronic, and Abbott outside the submitted work. Dr Pourfar reported receiving personal fees from Boston Scientific during the conduct of the study and personal fees from Boston Scientific outside the submitted work. Dr Mogilner reported receiving grants and personal fees from Boston Scientific during the conduct of the study. Dr Rosenow reported receiving research expenses and personal fees from Boston Scientific Neuromodulation during the conduct of the study and personal fees from Boston Scientific Neuromodulation outside the submitted work. Dr Neimat reported receiving personal fees from Medtronic, Abbott, and Boston Scientific outside the submitted work. Dr Ramirez-Zamora receiving reported serving on the advisory board of Boston Scientific during the conduct of the study; serving on the advisory board of Boston Scientific; and serving as a consultant for Medtronic outside the submitted work. Dr Pilitsis reported receiving grants and consulting fees from Boston Scientific during the conduct of the study; grants from Medtronic, Boston Scientific, Abbott, Focused Ultrasound Foundation, and the National Institutes of Health outside the submitted work; serving as the medical advisor for Aim Medical Robotics; and holding stock equity in Aim Medical Robotics. Dr Park reported receiving personal fees from Boston Scientific outside the submitted work; research support from the National Institutes of Health; personal fees from Zimmer Biomet, Smart Implant Systems/SynerFuse, Abbott, NeuroOne, Medtronic, and St. Jude Medical outside the submitted work; holding a patent for epilepsy treatment; and serving on the board for the Minnesota chapter of the American Parkinsons Disease Association. Dr Vitek reported receiving personal fees from Boston Scientific, nonfinancial support from Boston Scientific IPG's for nonhuman primate research, personal fees from Medtronic and Abbott during the conduct of the study; personal fees from Boston Scientific, Medtronic, Abbott, Surgical Information Sciences, Supernus, and Cala Health; and serving on the advisory board for Surgical Information Systems outside the submitted work. No other disclosures were reported. Dr Tröster reported receiving personal fees and consulting fees from Boston Scientific during the conduct of the study. Dr ul Haq reported serving on the advisory board of Boston Scientific outside the submitted work; serving as an investigator on ongoing grants supported directly or indirectly by Boston Scientific; speaking honoraria from Michael J. Fox Foundation and Parkinson's Association of Southwest Florida; and serving on the Data Safety Monitoring board for a Tourette trial outside the submitted work. Dr Okun reported receiving grants from the National Institutes of Health, Tourette Association of America, Michael J Fox Foundation, and Parkinson’s Foundation; royalties from Books4Patients; speaker fees from Movement Disorders Society and American Academy of Neurology; and continuing medical education courses and steering committees from Medscape, WebMD, MedEdicus, Academy of Learning Healthcare, Boston University CME, and Vanderbilt University outside the submitted work. Dr Foote reported receiving grants and personal fees from Medtronic and Boston Scientific, and grants from Abbott/St. Jude Medical and Functional Neuromodulation outside the submitted work. Dr Ponce reported receiving personal fees from Medtronic, Boston Scientific, and Abbott outside the submitted work. Dr Luca reported receiving research grants from Abbott and Boston Scientific outside the submitted work; consulting fees from Boston Scientific; speaking fees from Abbott, Boston Scientific, and Medtronic; and serving on the advisory boards for AbbVie, Supernus, and Amneal. Dr Jagid reported receiving grants from Boston Scientific, and grants and personal fees from Medtronic outside the submitted work. Dr Mandybur reported receiving grants and personal fees from Boston Scientific, Abbott, and Nevro outside the submitted work. Dr Phibbs reported receiving consulting fees from Medtronic and Boston Scientific.

Figures

Figure 1.
Figure 1.. Outcomes at Screening up to 5 Years Postrandomization for Unified Parkinson’s Disease Rating Scale (UPDRS-III) Motor Scores, Parkinsonian-Medicine Usage, Patient Satisfaction With Treatment, and Quality Of Life
A, UPDRS-III motor scores: the y-axis indicates mean UPDRS-III scores in the stimulation-on and medications-off condition. Box and whiskers indicate 5% to 95% tails, and diamond indicates mean). From screening, a significant improvement in motor outcomes is reported 1 year after deep brain stimulation (DBS) and sustained out to 5 years. B, levodopa equivalent daily dose (LEDD) in mg: the y-axis indicates mean LEDD from screening through the 5-year follow-up at each screening and yearly visit. Box and whiskers indicate 5% to 95% tails, and diamond indicates mean. From screening, there is a statistically significant reduction in medication 1 year after DBS implant sustained out to 5 years. C, Treatment Satisfaction Questionnaire: participants rated their satisfaction and if they would recommend the treatment to a friend with Parkinson disease. The y-axis shows the percentage of participants expressing satisfaction or dissatisfaction with DBS treatment, with different degrees of satisfaction or dissatisfaction indicated by shades of blue (satisfied) or orange (dissatisfied). On average, 94% of participants were satisfied while 6% of participants were dissatisfied across the 5-year follow-up. Error bars represent SE of the mean. D, Quality of life (Parkinson's Disease Questionnaire-39 [PDQ-39] index score): the PDQ-39 index score is derived from 39 items grouped into the 8 domains shown. Each item is scored on a 5-point Likert scale, with scores ranging from 0 (no problems at all) to 100 (maximum level of problems). The index score is the mean of the 8 individual scale scores. Improvement in this score returned to screening values by year 5 (5% improvement; P = .18). The most pronounced sustained improvements at year 5 are seen in the domains of bodily discomfort, activities of daily living, and stigma. aP < .001 for screening vs year 1 and screening vs year 5.
Figure 2.
Figure 2.. Evaluation of Unified Parkinson’s Disease Rating Scale (UPDRS-III) Motor Symptom Subcategories at Screening and Year 1 and Year 5 Postrandomization
Screening in medication-off condition only but year 1 and year 5 are medication-off, stimulation-on condition. The y-axis indicates mean score from screening through year 1 and year 5 postrandomization. Box and whiskers indicate 5% to 95% tails, diamond indicates mean. aP < .001.
See this image and copyright information in PMC

References

    1. Vitek JL, Jain R, Chen L, et al. Subthalamic nucleus deep brain stimulation with a multiple independent constant current-controlled device in Parkinson’s disease (INTREPID): a multicentre, double-blind, randomised, sham-controlled study. Lancet Neurol. 2020;19(6):491-501. doi: 10.1016/S1474-4422(20)30108-3 - DOI - PubMed
    1. Weaver FM, Follett K, Stern M, et al. ; CSP 468 Study Group . Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301(1):63-73. doi: 10.1001/jama.2008.929 - DOI - PMC - PubMed
    1. Deuschl G, Schade-Brittinger C, Krack P, et al. ; German Parkinson Study Group, Neurostimulation Section . A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355(9):896-908. doi: 10.1056/NEJMoa060281 - DOI - PubMed
    1. Okun MS, Gallo BV, Mandybur G, et al. ; SJM DBS Study Group . Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomised controlled trial. Lancet Neurol. 2012;11(2):140-149. doi: 10.1016/S1474-4422(11)70308-8 - DOI - PubMed
    1. Defer GL, Widner H, Marié RM, Rémy P, Levivier M. Core assessment program for surgical interventional therapies in Parkinson’s disease (CAPSIT-PD). Mov Disord. 1999;14(4):572-584. doi: 10.1002/1531-8257(199907)14:4<572::AID-MDS1005>3.0.CO;2-C - DOI - PubMed

Publication types