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Methylphenidate

A Treatment for Parkinson’s Disease?

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Abstract

Parkinson’s disease (PD) affects about 1 % of the population over the age of 60 years and is characterized by a combination of rest tremor, bradykinesia, rigidity, postural instability, stooped posture and freezing of gait (FoG). However, the clinical spectrum also spans a wide range of non-motor symptoms, such as depression, apathy, cognitive disorders, sleepiness, fatigue and pain. Given that the loss of dopamine in the striatum is the primary pathochemical hallmark in PD, pharmacological treatment of the disease has focused on restoring dopaminergic neurotransmission. The currently licensed dopaminergic treatments for PD modulate all the key steps in the dopamine transmission except the most powerful determinant of extracellular dopamine concentrations: the presynaptic dopamine transporter (DaT). Methylphenidate is a CNS stimulant that blocks the DaT and the noradrenaline (norepinephrine) transporter in the striatum and the prefrontal cortex in particular. Here, we report on and discuss the main open-label studies and randomized controlled trials on the effect of methylphenidate on severe gait disorders (e.g. the FoG) and non-motor symptoms in advanced PD. The various pharmacodynamic effects of methylphenidate mean that the drug may have significant value in the treatment of PD. However, there is a lack of randomized controlled trials in this field. Furthermore, more rigorous selection of the types and doses of the associated dopaminergic treatments is required because these parameters may profoundly influence the mechanisms of action of methylphenidate and the clinical outcomes. Pharmacogenetic tools could be of use in better defining study patients as a function of their dopaminergic metabolism and drug responsiveness.

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Acknowledgments

The authors wish to thank Dr. David Fraser (Biotech Communication, Damery, France) for helpful comments on the manuscript’s English. No particular funding was received for preparation of this article. The authors have no financial disclosures to make or potential conflicts of interest to report in relation to this article. Novartis provided the methylphenidate and the placebo for the randomized controlled trial mentioned above [37]. Caroline Moreau has served on the Scientific Advisory Board for Aguettant. Arnaud Delval has no disclosures to report. Luc Defebvre has served on the Scientific Advisory Board for Novartis and Aguettant. He has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson’s disease at symposia (Abbott and Boheringer). Kathy Dujardin has served on the Scientific Advisory Board for Novartis. She has received a grant from the MJ Fox Foundation for Parkinson’s disease research. Régis Bordet receives funding from the French Ministry of Research. He has received various honoraria from pharmaceutical companies for consultancy and lectures at symposia. David Devos has served on the Scientific Advisory Board for Novartis and Aguettant and has received PHRC grants from the French Ministry of Health and research funding from the ARSLA charity. He has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson’s disease at symposia. The authors contributed to the research project (1)(a) conception, (b) organization and (c) execution; and the manuscript (2)(a) writing of the first draft and (b) review and critical comment as follows: David Devos: 1a,b,c and 2a,b; Caroline Moreau: 1a,b,c and 2a; Arnaud Delval: 1a,b,c and 2a; Kathy Dujardin: 1a,b,c and 2b; Luc Defebvre: 2b and Régis Bordet: 2b.

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Authors and Affiliations

  1. Department of Medical Pharmacology, EA 1046, Lille Nord de France University, CHU Lille, Lille, France

    David Devos & Regis Bordet

  2. EA 4559, Lille Nord de France University, CHU Lille, Lille, France

    David Devos, Caroline Moreau, Arnaud Delval, Kathy Dujardin & Luc Defebvre

  3. Department of Movement Disorders and Neurology, Lille Nord de France University, CHU Lille, Lille, France

    Caroline Moreau, Kathy Dujardin & Luc Defebvre

  4. Department of Clinical Neurophysiology, Lille Nord de France University, CHU Lille, Lille, France

    Arnaud Delval

  5. Clinical Pharmacology Department, University of Lille Nord de France/Lille University Medical Center, 59037, Lille, France

    David Devos

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  1. David Devos
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  2. Caroline Moreau
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  3. Arnaud Delval
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Correspondence to David Devos.

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Devos, D., Moreau, C., Delval, A. et al. Methylphenidate. CNS Drugs 27, 1–14 (2013). https://doi.org/10.1007/s40263-012-0017-y

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