Can therapeutic strategies prevent and manage dyskinesia in Parkinson’s disease? An update

ABSTRACT

Introduction: Dyskinesia is a motor complication of Parkinson’s disease (PD) characterized by clinical heterogeneity and complex pathogenesis and associated with long-term levodopa therapy. Recent and controversial views on the management of PD patients have suggested that overall dyskinesia rates, and particularly troublesome dyskinesia, may be declining due to more conservative levodopa dosing regimens, widespread availability and early introduction of deep brain stimulation, and use of continuous drug delivery strategies. Nevertheless, anti-dyskinetic agents continue to be evaluated in clinical trials and recent efforts have focused on non-dopaminergic drugs.

Areas covered: In this review, the authors discuss the clinical phenomenology and current understanding of dyskinesia in PD with a focus on up-to-date therapeutic strategies to prevent and manage these drug-related involuntary movements.

Expert opinion: The way dyskinesia in PD is currently managed should be changed and attention should be focused toward a more personalized medicine rather than a one-fits-all-approach. The correct identification of dyskinesia types and tailored treatments are crucial for a better management of these involuntary movements together with a holistic approach which considers additional influencing factors. The future for dyskinesia treatment is likely to be found in non-dopaminergic approaches, first set into motion by the introduction of amantadine.

KEYWORDS:

• Dyskinesia
• Parkinson’s disease
• prevention
• treatment
• motor complications

Article highlights

• Dyskinesia is a major complication of chronic levodopa therapy; however, overall dyskinesia rates, and particularly troublesome dyskinesia, may be declining due to progress in the management of Parkinson’s disease.

• Dyskinesia is a heterogenous clinical phenomenon with a complex and still unclear pathogenesis where both dopaminergic and non-dopaminergic pathways are involved.

• Dopamine agonist monotherapy is reported to be associated with a delayed onset of dyskinesia although recent real-life data dispute this finding and its use in the long term provides inadequate motor control compared to levodopa-based therapies.

• Amantadine and clozapine (an atypical neuroleptic) are the only available oral drugs effective for the treatment of dyskinesia according to published evidence-based committees (Movement Disorder Society); however, other molecules, such as zonisamide, are also used. Advanced therapies, including intrajejunal levodopa infusion, deep brain stimulation, and unilateral pallidotomy, are also effective in a selected cohort of PD patients.

• A range of drugs with non-dopaminergic mechanisms of action are currently under investigation for dyskinesia and the results are awaited with interest.

This box summarizes key points contained in the article.

Acknowledgments

The authors acknowledge the support of the Movement Disorder Society Non-Motor PD Study Group, the National Institute for Health Research (NIHR) London South Clinical Research Network and the NIHR Biomedical Research Centre. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Declaration of interest

V Leta reports grants from BRC and Parkinson’s UK, a travel grant from Bial UK Ltd, and compensation for speaker-related activities from UCB and Britannia Pharmaceuticals outside the submitted work. P Jenner has received honoraria for consultancies and advisory boards from AbbVie, Adamas, BIAL, Britannia Pharmaceuticals, FP Pharmaceuticals, Kyowa Hakko Kirin, Lundbeck, New β Innovations, Profile Pharma, UCB, Worldwide Clinical Trials and Zambon outside the submitted work. KR Chaudhuri reports personal fees from Abbvie, Britannia Pharmaceuticals, UCB, Mundipharma, Zambon, Global Kinetics and Bial, grants from Parkinson’s UK, NIHR, PDNMG, Kirby Laing and NPF, and other from AbbVie, UCB, Sunovion, Pfizer, Jazz Pharma, Bial and Global Kinetics outside the submitted work. A Antonini has received compensation for consultancy and speaker-related activities from UCB, Boston Scientific, Boehringer Ingelheim, AbbVie and Zambon, and has received research support from Mundipharma outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.