A Real-Life Search for the Optimal Set of Conversion Factors to Levodopa-Equivalent-Dose in Parkinson's Disease Patients on Polytherapy.


Journal

Journal of Parkinson's disease
ISSN: 1877-718X
Titre abrégé: J Parkinsons Dis
Pays: Netherlands
ID NLM: 101567362

Informations de publication

Date de publication:
2020
Historique:
pubmed: 24 12 2019
medline: 20 4 2021
entrez: 24 12 2019
Statut: ppublish

Résumé

A wide variety of conversion factors for a levodopa-equivalent-dose (LED) have been proposed for each Parkinson's disease (PD) medication. The currently-used set of conversion factors is based on studies that relied on subjective experience or theoretical assumptions. This set was never validated in patients receiving polytherapy. To use real-life data to identify an optimal set of conversion factors independent of prior assumptions regarding clinical efficacy of different medications. Retrospective analysis of data from 206 cognitively-preserved patients with advanced PD receiving polytherapy before deep brain stimulation (DBS) surgery. A nonlinear automated problem solver was used to find a set of conversion factors that, when applied, minimized the coefficient of variation of LEDs in a relatively homogenous cohort of patients. Independent and model-free evaluation of a wide range of possible sets of conversion factors to LED suggested a set of normalized conversion factors for immediate release levodopa (1.00), controlled release levodopa (0.88), and amantadine (1.23). A minimal clinical benefit of entacapone was observed for patients with motor fluctuations. Our analysis could not detect conversion factors for dopamine agonists and MAO-B inhibitors, possibly because their clinical contribution when added to levodopa is limited. Independent from previous studies and prior assumptions we show that the currently-used LED conversion factors for immediate release levodopa, controlled release levodopa and amantadine are largely correct and that dopamine agonists, MAO-B inhibitors and entacapone, given in addition to levodopa, have little additional clinical value for PD patients with motor fluctuations.

Sections du résumé

BACKGROUND
A wide variety of conversion factors for a levodopa-equivalent-dose (LED) have been proposed for each Parkinson's disease (PD) medication. The currently-used set of conversion factors is based on studies that relied on subjective experience or theoretical assumptions. This set was never validated in patients receiving polytherapy.
OBJECTIVES
To use real-life data to identify an optimal set of conversion factors independent of prior assumptions regarding clinical efficacy of different medications.
METHODS
Retrospective analysis of data from 206 cognitively-preserved patients with advanced PD receiving polytherapy before deep brain stimulation (DBS) surgery. A nonlinear automated problem solver was used to find a set of conversion factors that, when applied, minimized the coefficient of variation of LEDs in a relatively homogenous cohort of patients.
RESULTS
Independent and model-free evaluation of a wide range of possible sets of conversion factors to LED suggested a set of normalized conversion factors for immediate release levodopa (1.00), controlled release levodopa (0.88), and amantadine (1.23). A minimal clinical benefit of entacapone was observed for patients with motor fluctuations. Our analysis could not detect conversion factors for dopamine agonists and MAO-B inhibitors, possibly because their clinical contribution when added to levodopa is limited.
CONCLUSIONS
Independent from previous studies and prior assumptions we show that the currently-used LED conversion factors for immediate release levodopa, controlled release levodopa and amantadine are largely correct and that dopamine agonists, MAO-B inhibitors and entacapone, given in addition to levodopa, have little additional clinical value for PD patients with motor fluctuations.

Identifiants

pubmed: 31868682
pii: JPD191769
doi: 10.3233/JPD-191769
doi:

Substances chimiques

Antiparkinson Agents 0
Catechols 0
Dopamine Agonists 0
Monoamine Oxidase Inhibitors 0
Nitriles 0
Levodopa 46627O600J
entacapone 4975G9NM6T
Amantadine BF4C9Z1J53

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

173-178

Auteurs

Muneer Abu Snineh (MA)

Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel.

Amal Hajyahya (A)

School of Pharmacy, Faculty of Medicine, the Hebrew University, Jerusalem, Israel.

Eduard Linetsky (E)

Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel.

Renana Eitan (R)

Department of Medical Neurobiology (Physiology), Institute of Medical Research - Israel-Canada, the Hebrew University - Hadassah Medical School and the Edmond and Lily Safra Center for Brain Research, the Hebrew University, Jerusalem, Israel.
Jerusalem Mental Health Center, Hebrew University Medical School, Jerusalem, Israel.

Hagai Bergman (H)

Department of Medical Neurobiology (Physiology), Institute of Medical Research - Israel-Canada, the Hebrew University - Hadassah Medical School and the Edmond and Lily Safra Center for Brain Research, the Hebrew University, Jerusalem, Israel.

Zvi Israel (Z)

Department of Neurosurgery, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel.

David Arkadir (D)

Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel.

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Classifications MeSH