Treatment of Levodopa-Induced Dyskinesias
For peak-dose dyskinesias—the most common type—reduce individual levodopa doses and add amantadine, which is the only medication proven to reduce established dyskinesia without compromising antiparkinsonian benefit. 1, 2
Identify the Dyskinesia Type First
The treatment strategy depends entirely on when dyskinesias occur relative to levodopa dosing:
Peak-Dose Dyskinesia (Most Common)
- Reduce individual levodopa doses while maintaining total daily dose by increasing dosing frequency 1
- Add amantadine as the only medication with demonstrated ability to reduce established dyskinesia expression without reducing antiparkinsonian benefit 2, 3
- Add dopamine agonists (pramipexole starting 0.125 mg titrated to 0.5 mg, or ropinirole starting 0.25 mg titrated to 4 mg) to allow further levodopa dose reduction 1, 3
- Consider COMT inhibitors (entacapone or tolcapone) to extend levodopa half-life and smooth plasma levels, though tolcapone requires hepatotoxicity monitoring 3, 4
Off-Period Dystonia
- Baclofen is the first-line oral agent 1
- Botulinum toxin injections for focal dystonia 1
- Increase levodopa bioavailability by optimizing timing and protein redistribution 5, 6
Diphasic Dyskinesia (Most Difficult)
- Fractionate levodopa dosing into smaller, more frequent doses 1
- Deep brain stimulation is often required when medical management fails, as this type is particularly resistant to pharmacological approaches 1, 2
Optimize Levodopa Delivery
Even when treating dyskinesias, maintain proper levodopa administration:
- Take levodopa 30 minutes before meals to avoid protein interference with absorption 7, 6
- Implement protein redistribution: low-protein breakfast and lunch, normal protein intake only at dinner (0.8-1.0 g/kg body weight daily) 5, 6
- Monitor for complications of protein redistribution including weight loss, micronutrient deficits, and paradoxically worsening dyskinesias that may require levodopa dose reduction 5
Surgical Intervention
Deep brain stimulation of the subthalamic nucleus is highly effective for controlling troublesome dyskinesias when medical management fails 2, 8:
- Subthalamic nucleus (STN) DBS is preferred when medication reduction is a primary goal 6
- Globus pallidus internus (GPi) DBS should be considered if cognitive decline or depression risk is a significant concern 6
- DBS is particularly indicated for young-onset PD patients with diphasic dyskinesias 1
Critical Monitoring Parameters
- Monitor for excessive levodopa dosing signs: dyskinesias and blepharospasm 7
- Track body weight regularly as dyskinesias increase energy expenditure, and dose adjustments affect weight 5
- Supplement B-vitamins (B6, B12, folate) routinely, as levodopa metabolism depletes these and elevated homocysteine may worsen complications 9
- Supplement vitamin D as PD patients have lower levels and supplementation may slow disease progression 9
Common Pitfalls to Avoid
- Do not delay levodopa initiation to prevent dyskinesias—dyskinesia development correlates with disease duration, not cumulative levodopa exposure 8
- Do not use strict low-protein diets—these lack evidence and risk malnutrition 5, 6
- Do not assume all dyskinesias are the same—peak-dose, diphasic, and off-period dyskinesias require completely different treatment approaches 1
- Do not overlook amantadine—it remains the only proven anti-dyskinetic medication that doesn't compromise motor benefit 2, 3