What are the treatment options for severe dyskinesia with motor fluctuations in advanced Parkinson's disease (PD)?

From the Guidelines

For severe dyskinesia with motor fluctuations in advanced Parkinson's disease, I strongly recommend advising patients to try complying with a protein-redistribution dietary regimen to maximize levodopa absorption and efficacy, in addition to adjusting their medication regimen. This approach is based on the most recent and highest quality evidence available, which suggests that protein redistribution can improve motor function and disability, and increase the duration of the "ON" state 1.

Key Considerations

• The protein-redistribution dietary regimen involves taking levodopa medications at least 30 minutes before meals, and redistributing protein intake throughout the day, with a low-protein breakfast and lunch, and consumption of a second course with no quantitative restrictions in terms of protein only at dinner 1.
• This regimen can help maximize levodopa absorption and efficacy, particularly in patients experiencing motor fluctuations 1.
• Patients should undergo active monitoring to avoid potential complications, including weight loss, micronutrient deficits, hunger before dinner, and dyskinesias 1.
• The daily protein requirements should be set to 0.8-1.0 g/kg of body weight, and patients should be advised to distribute food intake throughout the day and divide protein intake 1.

Medication Adjustments

• Reducing individual levodopa doses while increasing frequency can help minimize peak-dose dyskinesias 1.
• Adding amantadine or other adjunctive therapies, such as dopamine agonists, COMT inhibitors, or MAO-B inhibitors, can help extend levodopa's effect and reduce dyskinesia 1.
• In severe cases unresponsive to medication adjustments, deep brain stimulation or continuous delivery systems like levodopa-carbidopa intestinal gel (LCIG) via jejunal tube or subcutaneous apomorphine infusion should be considered 1.

Conclusion is not allowed, so the answer just ends here.

From the FDA Drug Label

In Study 3 and Study 4, the primary measure of effectiveness was the change in the mean number of hours spent in the "OFF" state at baseline compared to the mean number of hours spent in the "OFF" state during the treatment period. In Study 3 and Study 4, rasagiline tablets 1 mg once daily reduced "OFF" time compared to placebo when added to levodopa in patients experiencing motor fluctuations (Tables 7 and 8). "Troublesome" dyskinesia is defined as dyskinesia that interferes with the patient's daily activity. In Study 3 and Study 4, dose reduction of levodopa was allowed within the first 6 weeks, if dopaminergic side effects developed including dyskinesia or hallucinations.

The treatment options for severe dyskinesia with motor fluctuations in advanced Parkinson's disease (PD) include:

• Rasagiline tablets 1 mg once daily to reduce "OFF" time when added to levodopa in patients experiencing motor fluctuations 2
• Dose reduction of levodopa if dopaminergic side effects develop, including dyskinesia or hallucinations 2 Key points to consider:
• Rasagiline tablets may help reduce "OFF" time in patients with advanced PD and motor fluctuations
• Levodopa dose reduction may be necessary to manage dopaminergic side effects, including dyskinesia 2

From the Research

Treatment Options for Severe Dyskinesia with Motor Fluctuations in Advanced Parkinson's Disease (PD)

• Medical management aims to extend levodopa benefit while minimizing motor complications, and includes manipulation of levodopa dose and the introduction of supplemental therapies such as catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, and dopamine agonists including apomorphine 3
• Device-aided therapies, such as levodopa/carbidopa intestinal gel infusion, deep brain stimulation, and MRI-guided focused ultrasound, may be considered when motor complications cannot be satisfactorily controlled with oral medications 3, 4
• Pharmacologic treatment options for motor fluctuations and dyskinesia include dopamine agonists, catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidase (MAO) B inhibitors, and amantadine 5
• Surgical options, such as deep brain stimulation and medial pallidotomy, may be considered for patients with severe dyskinesia and "off" periods that have not improved with pharmacologic therapy 5
• Continuous infusion of dopaminergic agents, such as subcutaneous apomorphine infusion or enteric L-DOPA delivery, may also be effective in managing dyskinesia and motor fluctuations 4

Specific Treatment Approaches

• Levodopa/carbidopa intestinal gel infusion (LCIG) has been shown to improve motor fluctuations and dyskinesias in patients with advanced Parkinson's disease, and may be particularly effective for patients with complex dyskinesias 6
• Deep brain stimulation, including closed-loop and adaptive stimulation, may be an effective treatment option for patients with severe dyskinesia and motor fluctuations 3
• Adenosine A2A receptor antagonists and enzyme inhibitors like opicapone and safinamide may also be useful in managing motor complications in Parkinson's disease 3