Current treatment and future prospects of dopa-induced dyskinesias

Drugs Today (Barc). 2015 May;51(5):315-29. doi: 10.1358/dot.2015.51.5.2313726.

Abstract

Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes difficult, so preventive strategies should be first evaluated. Although levodopa (LD) treatment has recently been related as risk factor for LID, the main strategy to delay LID is to start PD treatment with dopamine agonists, adding LD at low doses. After LID onset, approaches include reducing single LD doses, reducing or discontinuing monoamine oxidase type B/catechol O-methyltransferase (MAO-B/COMT) inhibitors and extended-release (ER) LD. Amantadine represents the best antidyskinetic tool, and ER amantadine is the most promising upcoming antidyskinetic drug. New LD formulations such as IPX-066 (able to provide continuous dopaminergic stimulation) also represent promising new approaches. The involvement of a nondopaminergic system in the pathogenesis of LID suggests that the modulation of glutamate, serotonin and adenosine could have potential as new upcoming drug targets, but the role of such drugs will still need to be confirmed in randomized controlled trials.

Keywords: Dopaminergic modulation; IPX-066; Levodopa-induced dyskinesias; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amantadine / administration & dosage
  • Amantadine / adverse effects
  • Amantadine / therapeutic use
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / adverse effects*
  • Antiparkinson Agents / therapeutic use
  • Carbidopa / administration & dosage
  • Carbidopa / adverse effects*
  • Carbidopa / therapeutic use
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Dyskinesia, Drug-Induced / drug therapy*
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / metabolism
  • Humans
  • Levodopa / administration & dosage
  • Levodopa / adverse effects*
  • Levodopa / therapeutic use
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / metabolism
  • Practice Guidelines as Topic
  • Treatment Outcome

Substances

  • Antiparkinson Agents
  • Delayed-Action Preparations
  • Drug Combinations
  • carbidopa, levodopa drug combination
  • Levodopa
  • Amantadine
  • Carbidopa