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. 2026 Jan 16;8(1):e001427.
doi: 10.1136/bmjno-2025-001427. eCollection 2026.

Understanding dopaminergic dose reduction following STN-DBS: mediation analysis

Aymeric Lanore  1 , Marion Houot  2 , Aymeric Basset  3 , David Bendetowicz  3 , Poornima J Menon  3 , Eric Bardinet  3 , Sara Fernandez Vidal  4 , Jordan Cornillault  3 , Carine Karachi  3 , Soledad Navarro  5 , Jonas Ihle  3 , Alexandre Eusebio  6 , Caroline Giordana  7 , Tiphaine Rouaud  8 , Sophie Drapier  9 , Dominique Guehl  10   11 , Ana Marques  12   13 , Cécile Hubsch  14 , Béchir Jarraya  15 , Isabelle Benatru  16 , Stephane Thobois  17 , Lucie Hopes  18 , David Maltete  19 , Olivier Rascol  20 , Melissa Tir  21 , Caroline Moreau  22 , Christine Tranchant  23 , Anne-Sophie Rolland  24 , David Devos  25 , Jean Christophe Corvol  1 , David Grabli  26 , Elodie Hainque  26 ; PREDISTIM study group
Collaborators, Affiliations

Understanding dopaminergic dose reduction following STN-DBS: mediation analysis

Aymeric Lanore et al. BMJ Neurol Open. .

Abstract

Background: Levodopa equivalent dopaminergic dose (LEDD) reduction after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease varies widely. Identifying predictors may guide patient selection and programming. Our objectives were to identify predictors of LEDD reduction and to test whether motor improvement mediates this association.

Methods: Data from 144 patients treated by STN-DBS were analysed. Predictors of LEDD reduction were selected using the Boruta algorithm, a machine-learning method comparing variable importance to randomised features and then tested in a structural equation model for direct and motor-mediated effects.

Results: Mean LEDD reduction was 41.7% (±38.2%) and motor improvement was 48.6% (±26.7%) at 1 year. Among the four predictors identified by Boruta, lower baseline LEDD (β=0.39, p=0.001), greater axial impairment (β=-0.25, p=0.003) and higher total volume of tissue activated (β=-0.17, p=0.031) were directly associated with lower LEDD reduction, independent of motor improvement. Sensorimotor STN overlap was not directly linked to LEDD reduction but was positively associated with motor improvement (β=0.34, p=0.001), which showed a trend-level effect on LEDD reduction (β=0.16, p=0.065). The total effect of sensorimotor STN overlap on LEDD reduction was not significant.

Discussion: Dopaminergic dose reduction after STN-DBS is constrained by preoperative axial symptoms and stimulation spread, independently of motor improvement, while sensorimotor STN overlap improves motor symptoms but not dose reduction. Integrating motor phenotype with anatomical guidance may enhance medication management post DBS.

Keywords: NEUROSURGERY; PARKINSON'S DISEASE; PHARMACOLOGY.

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Conflict of interest statement

AL, MH, AB, DB, PJM, EB, SFV, JC, CK, SN, JI: None declared. AE received research support from ANR, DGOS and France Parkinson charity; honouraria from AbbVie, Medtronic and Boston Scientific, and travel grants from Homeperf. CG reports honouraria from ABBOTT et ABBVIE. TR received honouraria from Medtronic, AbbVie, Elivie, Homeperf, Orkyn, Asdia and Novartis, outside the submitted work. SD received honouraria from Medtronic and Boston, outside the submitted work. D Guehl, AM, CH, BJ, IB: None declared. ST reports honouraria from Merz, AbbVie, Boston, Medtronic, Bial, travel grant from MDS, and grant from PHRC and Neurodis. LH, DM: None declared. OR has received financial compensation for scientific advice and consulting activities from AbbVie, Adamas, Acorda, Addex, Aguettant, Alkahest, AlzProtect, Apopharma, AstraZeneca, Bial, Biogen, Britannia, Buckwang, Cerevel, Clevexel, Irlab, Eli Lilly, Lundbeck, Neuroderm, ONO Pharma, Orion Pharma, Osmotica, Oxford Biomedica, Pfizer, Prexton Therapeutics, Sanofi, Servier, Sunovion, Théranexus, Takeda, Teva, UCB, Watermark Research, XenoPort, XO, Zambon and scientific grants from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, MJFox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020, Horizon Europe). MT reports honouraria and consultation fees from Boston Scientific, Medtronic, Adelia, Elivie and Aguettant, outside the submitted work. CM reports consultation fees from Boston Sci, Orkyn, Feet me Health, scientific grants from ANR, France Parkinson, Vaincre Parkinson, and equities from INBrain Pharma, InVenis Biotherapies. CT reports consultation fees from AbbVie and Linde, therapeutic studies with Roche, and participation in a meeting with Ipsen. A-SR: None declared. DD reports consultation fees from Scientific Advisory Board for AbbVie, Alterity, Orkyn, Air Liquide, Apopharma, Lundbeck, Everpharma, PTC Therapeutics, Boston Scientific, Cure Parkinson Trust, grants from French Ministry of Health: PHRC grants, French Ministry of Research: ANR, European Preclinical Research: Coen, European Clinical Research: Horizon 2020, Charities from France Parkinson, ARSLA Foundation, from Foundations: University of Lille, CA, and equities from InBrain Pharma, InVenis Biotherapies. J-CC has served in advisory boards for Alzprotect, Bayer, Biogen, Idorsia, Prevail Therapeutic, Servier, Theranexus, UCB; and received grants from Sanofi and the Michael J Fox Foundation, outside of this work. D Grabli: None declared. EH reports speech honouraria from Boston and Medtronic, travel grants from Merz and AbbVie.

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