Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals

Stefanie T Jost¹, Marie-Ann Kaldenbach¹, Angelo Antonini², Pablo Martinez-Martin³, Lars Timmermann⁴, Per Odin^{5

6}, Regina Katzenschlager⁷, Rupam Borgohain⁸, Alfonso Fasano^{9

10

11

12}, Fabrizio Stocchi¹³, Nobutaka Hattori¹⁴, Prashanth Lingappa Kukkle^{15

16}, Mayela Rodríguez-Violante^{17

18}, Cristian Falup-Pecurariu^{19

20}, Sebastian Schade²¹, Jan Niklas Petry-Schmelzer¹, Vinod Metta^{22

23}, Daniel Weintraub^{24

25}, Guenther Deuschl²⁶, Alberto J Espay²⁷, Eng-King Tan^{28

29}, Roongroj Bhidayasiri^{30

31}, Victor S C Fung³², Francisco Cardoso³³, Claudia Trenkwalder^{34

35}, Peter Jenner³⁶, K Ray Chaudhuri^{22

23

37}, Haidar S Dafsari¹; International Parkinson and Movement Disorders Society Non-Motor Parkinson Disease Study Group

Affiliations

¹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
² Parkinson and Movement Disorders Unit, Department of Neurosciences (DNS), University of Padua, Padova, Italy.
³ Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health, Madrid, Spain.
⁴ Department of Neurology, University Hospital Giessen and Marburg, Marburg, Germany.
⁵ Division of Neurology, Lund University, Lund, Sweden.
⁶ Department of Neurology, Skåne University Hospital, Lund, Sweden.
⁷ Department of Neurology, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders at Klinik Donaustadt, Vienna, Austria.
⁸ Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, India.
⁹ Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital-University Health Network (UHN), Toronto, Ontario, Canada.
¹⁰ Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
¹¹ Krembil Research Institute, Toronto, Ontario, Canada.
¹² Department of Parkinson's Disease & Movement Disorders Rehabilitation, Moriggia-Pelascini Hospital-Gravedona ed Uniti, Como, Italy.
¹³ University and Institute for Research and Medical Care IRCCS San Raffaele, Rome, Italy.
¹⁴ Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
¹⁵ Center for Parkinson's Disease and Movement Disorders, Manipal Hospital, Bangalore, India.
¹⁶ Parkinson's Disease and Movement Disorders Clinic, Bangalore, India.
¹⁷ Insituto Nacional de Neurologia y Neurocirugia, Movement Disorders Clinic, Mexico City, Mexico.
¹⁸ Movement Disorder Clinic, National Institute of Neurology and Neurosurgery, Mexico City, Mexico.
¹⁹ Department of Neurology, Faculty of Medicine, Transilvania University of Brașov, Brașov, Romania.
²⁰ Department of Neurology, County Emergency Clinic Hospital, Brașov, Romania.
²¹ Department of Clinical Neurophysiology, University Medical Center Göttingen, Göttingen, Germany.
²² Parkinson Foundation International Centre of Excellence, King's College Hospital, London, United Kingdom.
²³ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
²⁴ Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁵ Parkinson's Disease Research, Education and Clinical Center (PADRECC), Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
²⁶ Department of Neurology, University Hospital Schleswig-Holstein (UKSH), Christian-Albrechts-University Kiel, Kiel, Germany.
²⁷ University of Cincinnati Gardner Neuroscience Institute, Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.
²⁸ Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore.
²⁹ Neuroscience and Behavioral Disorders (NBD) Department, Duke-NUS Medical School, Singapore, Singapore.
³⁰ Chulalongkorn Centre of Excellence for Parkinson's Disease & Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
³¹ The Academy of Science, The Royal Society of Thailand, Bangkok, Thailand.
³² Movement Disorder Unit, Department of Neurology, Westmead Hospital, Westmead, Australia.
³³ Movement Disorders Unit, Internal Medicine Department, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
³⁴ Paracelsus-Elena-Klinik, Kassel, Germany.
³⁵ Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
³⁶ Institute of Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
³⁷ NIHR Mental Health Biomedical Research Centre and Dementia Biomedical Research Unit, South London and Maudsley NHS Foundation Trust and King's College London, London, United Kingdom.

PMID: 37147135
DOI: 10.1002/mds.29410

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals

Stefanie T Jost et al. Mov Disord. 2023 Jul.

. 2023 Jul;38(7):1236-1252.

doi: 10.1002/mds.29410. Epub 2023 May 5.

Authors

Affiliations

¹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
² Parkinson and Movement Disorders Unit, Department of Neurosciences (DNS), University of Padua, Padova, Italy.
³ Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health, Madrid, Spain.
⁴ Department of Neurology, University Hospital Giessen and Marburg, Marburg, Germany.
⁵ Division of Neurology, Lund University, Lund, Sweden.
⁶ Department of Neurology, Skåne University Hospital, Lund, Sweden.
⁷ Department of Neurology, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders at Klinik Donaustadt, Vienna, Austria.
⁸ Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, India.
⁹ Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital-University Health Network (UHN), Toronto, Ontario, Canada.
¹⁰ Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
¹¹ Krembil Research Institute, Toronto, Ontario, Canada.
¹² Department of Parkinson's Disease & Movement Disorders Rehabilitation, Moriggia-Pelascini Hospital-Gravedona ed Uniti, Como, Italy.
¹³ University and Institute for Research and Medical Care IRCCS San Raffaele, Rome, Italy.
¹⁴ Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
¹⁵ Center for Parkinson's Disease and Movement Disorders, Manipal Hospital, Bangalore, India.
¹⁶ Parkinson's Disease and Movement Disorders Clinic, Bangalore, India.
¹⁷ Insituto Nacional de Neurologia y Neurocirugia, Movement Disorders Clinic, Mexico City, Mexico.
¹⁸ Movement Disorder Clinic, National Institute of Neurology and Neurosurgery, Mexico City, Mexico.
¹⁹ Department of Neurology, Faculty of Medicine, Transilvania University of Brașov, Brașov, Romania.
²⁰ Department of Neurology, County Emergency Clinic Hospital, Brașov, Romania.
²¹ Department of Clinical Neurophysiology, University Medical Center Göttingen, Göttingen, Germany.
²² Parkinson Foundation International Centre of Excellence, King's College Hospital, London, United Kingdom.
²³ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
²⁴ Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁵ Parkinson's Disease Research, Education and Clinical Center (PADRECC), Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
²⁶ Department of Neurology, University Hospital Schleswig-Holstein (UKSH), Christian-Albrechts-University Kiel, Kiel, Germany.
²⁷ University of Cincinnati Gardner Neuroscience Institute, Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, Ohio, USA.
²⁸ Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore.
²⁹ Neuroscience and Behavioral Disorders (NBD) Department, Duke-NUS Medical School, Singapore, Singapore.
³⁰ Chulalongkorn Centre of Excellence for Parkinson's Disease & Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
³¹ The Academy of Science, The Royal Society of Thailand, Bangkok, Thailand.
³² Movement Disorder Unit, Department of Neurology, Westmead Hospital, Westmead, Australia.
³³ Movement Disorders Unit, Internal Medicine Department, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
³⁴ Paracelsus-Elena-Klinik, Kassel, Germany.
³⁵ Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
³⁶ Institute of Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
³⁷ NIHR Mental Health Biomedical Research Centre and Dementia Biomedical Research Unit, South London and Maudsley NHS Foundation Trust and King's College London, London, United Kingdom.

PMID: 37147135
DOI: 10.1002/mds.29410

Abstract

Background: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed.

Objectives: To update LED conversion formulae based on a systematic review.

Methods: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency.

Results: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon.

Conclusions: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: LEDD; levodopa equivalent daily dose; levodopa equivalent dose.

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References

1. Ray Chaudhuri K, Poewe W, Brooks D. Motor and nonmotor complications of levodopa: phenomenology, risk factors, and imaging features. Mov Disord 2018;33(6):909-919.
1. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord 2010;25(15):2649-2653.
1. Hamid E, Ayele BA, Massi DG, et al. Availability of therapies and services for Parkinson's disease in Africa: a continent-wide survey. Mov Disord 2021;36(10):2393-2407.
1. Bovolenta TM, de Azevedo Silva SMC, Saba RA, Borges V, Ferraz HB, Felicio AC. Average annual cost of Parkinson's disease in Sao Paulo, Brazil, with a focus on disease-related motor symptoms. Clin Interv Aging 2017;12:2095-2108.
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Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals

Affiliations

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical