Chemical management of levodopa-induced dyskinesia in Parkinson’s disease patients

ABSTRACT

Introduction: Levodopa-induced dyskinesias (LID) appears in more than 50% of Parkinson’s disease patients after 5 years of treatment and clinicians always have to ensure that there is a balance between the beneficial effect of the treatment and the potential complications.

Areas covered: In this review, the authors discuss the treatment of LID. Treatment can be divided into strategies for preventing their occurrence, modification of dopaminergic therapy, and providing more continuous dopaminergic stimulation as well as the use of nondopaminergic drugs.

Expert opinion: Amantadine is currently considered the most effective drug for the treatment of LID. Several compounds developed to target adenosine, adrenergic, glutamatergic, and serotonergic receptors have shown to significantly decrease dyskinesias in animal models. However, despite promising preclinical results, translation to clinical practice remains challenging and majority of these compounds failed to decrease LID in randomized controlled trials with moderate–to-advanced parkinsonian patients. Despite promising results with nondopaminergic drugs, treatment of dyskinesias is still challenging and largely due to their side effects. Future research should focus on developing treatments that can provide continuous dopaminergic delivery throughout the day in a noninvasive manner. Studies on the impact of the early administration of long-acting formulations of levo-3,4-dihydroxy-phenylalanine on dyskinesias are also necessary.

KEYWORDS:

• Parkinson’s disease
• dyskinesias; treatment

Article highlights

• Levodopa-induced dyskinesias can be manifested as peak dose, biphasic, and end-of-dose dyskinesias.

• The dopaminergic degeneration and l-DOPA administration are main factors in developing dyskinesias.

• Initial treatment with dopamine agonist decreases the incidence of dyskinesias but decision on initial treatment has no long-term effect and all patients will eventually require levodopa.

• Amantadine is the only approved antidyskinetic drug.

• Promising results on the ability of glutamatergic antagonist dipraglurant and serotonergic agonist eltoprazine to reduce dyskinesia without an effect on motor response to levodopa deserve further investigation.

This box summarizes key points contained in the article.

Declaration of interest

V Kostic has received grant support from the Ministry of Education and Science of the Republic of Serbia and from the Serbian Academy of Arts and Sciences, as well as research grants from Stada, Valeant, Boehringer Ingelheim and Novartis. He has also received lecturing fees from Stada, Boehringer Ingelheim and Novartis. I Petrovic has received a grant from the Ministry of Education and Science of the Republic of Serbia and from the Academy of Arts and Sciences. They have also received a travel grant from Novartis as well as speaker’s honoraria from Boehringer Ingelheim, ElPharma and GlaxoSmithKline. 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.

Additional information

Funding

This article is support by a research grant (grant no. 17590) from the Ministry of Education and Science of the Republic of Serbia via V Kostic.