Chapter 18  ·  Module 3
Motor Complications of Long-Term Levodopa Therapy
Wearing-off, on-off fluctuations, dyskinesias, and management
Complication Comparison
Wearing-Off On-Off Fluctuations Dyskinesias
Timing End of dose interval Unpredictable Peak dose (most common)
Pattern Predictable return of motor symptoms Abrupt on-off switching Involuntary choreiform movements
Cause Short levodopa half-life; lost dopamine buffering Pharmacokinetic instability plus receptor changes Excess dopamine at striatum
Management More frequent doses; adjunctive drugs Continuous delivery; dopamine agonists Reduce dose; amantadine
Management Strategies
For Wearing-Off
Smooth and Extend Levodopa Effect
  • Smaller, more frequent doses
  • Extended-release carbidopa-levodopa
  • Add monoamine oxidase B inhibitor
  • Add catechol-O-methyltransferase inhibitor
  • Add dopamine agonist
For Dyskinesias
Reduce Peak Dopamine Stimulation
  • Reduce individual levodopa dose
  • Add amantadine (N-methyl-D-aspartate antagonist)
  • Continuous levodopa-carbidopa intestinal gel infusion for refractory cases