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Contemporary Options for the Management of Motor Complications in Parkinson’s Disease: Updated Clinical Review

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Abstract

Parkinson’s disease (PD) is a chronic, progressive condition affecting around 1% of the population older than 60 years. Upon long-term treatment with levodopa, the mainstay of treatment in PD, most patients, especially younger ones exposed to higher doses, will experience symptoms related to end-of-dose deterioration, peak-dose dyskinesias, and other motor fluctuations. Therapeutic strategies are grounded on modification of oral levodopa pharmacokinetics to extend levodopa benefit and development of new routes of drug delivery (e.g., levodopa/carbidopa intestinal gel infusion) or long-acting formulations of existing dopaminergic drugs to prolong the duration of striatal dopamine receptors stimulation. As our understanding of the pathophysiology of motor complications evolves, our therapeutic armamentarium is actively expanding and the focus of research is now actively pointing to the new non-dopaminergic agents acting both within the basal ganglia and in other brain regions (e.g., drugs acting on glutamate, GABA, serotonin, and calcium channels). Despite the fact that trials comparing the different therapeutic strategies are lacking, we aimed at devising practical evidence- and experience-guided suggestions for the clinical management of motor complications, emphasizing that this should always be an individualized endeavor. This review summarizes the pharmacological management of motor complications in PD, including new formulations and routes of delivery, and the newer released drugs such as istradefylline, opicapone, safinamide, and zonisamide. Advanced therapeutic strategies for selected cases such as treatment with apomorphine and surgical techniques (deep brain stimulation) are also discussed. A comprehensive knowledge of the available options and evidence is fundamental for the successful management of these challenging complications.

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Authors and Affiliations

  1. Department of Neurology, Centro Hospitalar Universitário de S. João, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal

    Verónica Cabreira & João Massano

  2. Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Porto, Portugal

    Verónica Cabreira & João Massano

  3. Department of Biomedicine, Pharmacology and Therapeutics Unit, Faculty of Medicine, University of Porto, Porto, Portugal

    Patrício Soares-da-Silva

  4. MedInUP, Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal

    Patrício Soares-da-Silva

  5. Department of Research and Development, BIAL, Portela & Cª S.A., S. Mamede do Coronado, Portugal

    Patrício Soares-da-Silva

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  1. Verónica Cabreira
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Verónica Cabreira has received financial support to attend scientific meetings from Roche. João Massano received advisor honoraria from Bial, Merck Sharp and Dohme, and Zambon; he received financial support to speak at or attend meetings from Bial, Boston Scientific, GE Healthcare, Grunenthal, Medtronic, and Novartis. Patrício Soares-da-Silva is employed by Bial—Portela & Cª, S.A.

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Cabreira, V., Soares-da-Silva, P. & Massano, J. Contemporary Options for the Management of Motor Complications in Parkinson’s Disease: Updated Clinical Review. Drugs 79, 593–608 (2019). https://doi.org/10.1007/s40265-019-01098-w

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