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

Author:

Jost Stefanie T.1ORCID,Kaldenbach Marie‐Ann1,Antonini Angelo2ORCID,Martinez‐Martin Pablo3ORCID,Timmermann Lars4,Odin Per56,Katzenschlager Regina7,Borgohain Rupam8,Fasano Alfonso9101112ORCID,Stocchi Fabrizio13,Hattori Nobutaka14,Kukkle Prashanth Lingappa1516ORCID,Rodríguez‐Violante Mayela1718ORCID,Falup‐Pecurariu Cristian1920,Schade Sebastian21ORCID,Petry‐Schmelzer Jan Niklas1ORCID,Metta Vinod2223,Weintraub Daniel2425ORCID,Deuschl Guenther26ORCID,Espay Alberto J.27ORCID,Tan Eng‐King2829,Bhidayasiri Roongroj3031ORCID,Fung Victor S.C.32ORCID,Cardoso Francisco33ORCID,Trenkwalder Claudia3435,Jenner Peter36,Ray Chaudhuri K.222337,Dafsari Haidar S.1,

Affiliation:

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

Abstract

AbstractBackgroundTo 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.ObjectivesTo update LED conversion formulae based on a systematic review.MethodsThe 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.ResultsThe 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.ConclusionsThe 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.

Publisher

Wiley

Subject

Neurology (clinical),Neurology

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