What are the treatment options for dyskinesia in Parkinson's disease?

Treatment Options for Dyskinesia in Parkinson's Disease

Amantadine is the first-line medication for treating levodopa-induced dyskinesia in Parkinson's disease, with extended-release formulations showing significant improvement in activities of daily living affected by dyskinesia. 1

Understanding Dyskinesia in Parkinson's Disease

Dyskinesia in Parkinson's disease primarily occurs as a complication of long-term levodopa therapy. It manifests as involuntary movements that can significantly impact quality of life. Based on their temporal relationship to levodopa dosing, dyskinesias are classified into three main types:

1. Peak-dose dyskinesia - Most common type, occurring when levodopa-derived dopamine peaks in the brain 2, 3
2. Off-period dyskinesia - Occurs when medication effect wears off 2
3. Diphasic dyskinesia - Occurs at the beginning and end of a dose's effectiveness 2

Treatment Algorithm for Dyskinesia

First-Line Approaches:

1. Identify dyskinesia type and adjust levodopa regimen:

   • For peak-dose dyskinesia: Reduce individual doses of levodopa and administer more frequent, smaller doses 2
   • For off-period dyskinesia: Consider adding longer-acting dopamine agonists 2
   • For diphasic dyskinesia: Fractionate levodopa dosage throughout the day 2

2. Add amantadine:

   • Currently the only medication with demonstrated ability to reduce established dyskinesia without reducing antiparkinsonian benefit 3
   • Extended-release formulations (ADS-5102) significantly reduce the impact of dyskinesia on activities of daily living 1
   • Dosing: Start with lower doses and titrate based on response and tolerability

Second-Line Approaches:

1. Dopamine agonists:

   • Can be added to a reduced levodopa regimen to maintain motor control while minimizing dyskinesia 2, 4
   • Useful particularly for peak-dose dyskinesia 2

2. COMT inhibitors or MAO-B inhibitors:

   • Can help manage motor fluctuations that may contribute to dyskinesia 5
   • Should be used cautiously as they may sometimes worsen dyskinesia

3. For off-period dystonia:

   • Baclofen may be beneficial 2
   • Botulinum toxin injections for focal dystonia 2

Advanced Therapies (for refractory cases):

1. Deep Brain Stimulation (DBS):

   • Most effective surgical intervention for dyskinesia 2, 3
   • Particularly useful for diphasic dyskinesias that are difficult to manage medically 2
   • Subthalamic nucleus stimulation is very effective in treating levodopa-induced dyskinesia 3

2. Continuous medication delivery systems:

   • Levodopa-carbidopa intestinal gel infusion 5
   • Continuous subcutaneous levodopa infusion 5

Practical Management Tips

• Take levodopa 30 minutes before meals to maximize absorption 5
• Consider protein redistribution diet (low-protein breakfast/lunch, normal protein dinner) for patients with motor fluctuations 5
• Use the lowest effective dose of levodopa to minimize side effects 5
• Regular monitoring for worsening dyskinesia is essential 5
• For patients with troublesome dyskinesia, the Unified Dyskinesia Rating Scale (UDysRS) can help assess severity and impact on daily activities 1

Emerging Treatments

Research is ongoing for new treatments targeting non-dopaminergic pathways:

• Antiepileptic medications 3
• Serotonergic medications 3, 6
• Novel formulations of existing medications 6

Cautions and Monitoring

• Monitor for impulse control disorders with dopaminergic medications 7
• Regular assessment of hepatic, hematopoietic, cardiovascular, and renal function during extended therapy 7
• Be aware that hallucinations and psychotic-like behavior can occur with dopaminergic medications 7
• Monitor for melanoma, as Parkinson's disease patients have a higher risk 7

By following this structured approach to managing dyskinesia in Parkinson's disease, clinicians can significantly improve patients' quality of life and functional capacity while minimizing the impact of these troublesome motor complications.