Managing Dyskinesia Amid Advancements in Parkinson Disease Therapies

Panelists discuss how recent advancements in Parkinson disease treatment include 3 newly approved medications—an oral extended-release carbidopa-levodopa with mucoadhesive properties, a subcutaneous foslevodopa infusion, and a subcutaneous apomorphine infusion—that aim to provide more continuous dopamine stimulation and reduce motor fluctuations by offering longer-lasting benefits and smoother symptom control compared with traditional immediate-release formulations.

Panelists discuss how newer Parkinson disease therapies may impact dyskinesia management by potentially providing continuous dopaminergic stimulation that could prevent dyskinesia development if used early, though current evidence from phase 3 trials shows mixed results with improvements in good ON time (ON time without troublesome dyskinesia) but limited reduction in existing troublesome dyskinesia, suggesting that while these treatments offer promise, more research is needed to determine their effectiveness in reducing dyskinesia in patients who already experience it.

Panelists discuss how dyskinesia affects 30% to 50% of Parkinson patients by 5 years and over 90% by 10 years, creating significant functional limitations including impaired writing, eating, and dressing abilities, increased fall risk, job performance challenges, social isolation due to embarrassment about abnormal movements, and restrictions on therapeutic options since increasing levodopa doses to manage OFF time would worsen dyskinesia, ultimately impacting both patients' basic human dignity and their caregivers' quality of life.

Panelists discuss how a 54-year-old woman with early-onset Parkinson disease presenting with troublesome peak-dose dyskinesia affecting her work performance illustrates the challenge of managing patients who have both dyskinesia and likely OFF episodes, requiring careful assessment of functional impacts through targeted questioning about daily activities, work performance, and social interactions, since patients often minimize or remain unaware of their dyskinesia's true impact while caregivers may provide crucial insights into how the involuntary movements affect not only the patient but also family dynamics and professional relationships.

Panelists discuss how delayed-release/extended-release amantadine represents a unique treatment option for patients like the 54-year-old woman with both dyskinesia and “off” time, as it is the only FDA-approved medication that addresses both conditions simultaneously, with its bedtime dosing and pharmacokinetic profile providing overnight absorption and sustained daytime levels that resulted in phase 3 trials showing a 40% reduction in dyskinesia and 2.4 hours of increased good “on” time, making it an ideal first-line treatment for patients who have both troublesome dyskinesia and motor fluctuations rather than simply reducing dopaminergic medications which would worsen motor symptoms.

Panelists discuss how treatment options for advanced Parkinson disease patients like the 54-year-old woman include deep brain stimulation (DBS) as an excellent choice given her young age and cognitive status, with amantadine delayed-release/extended-release showing robust effects comparable to DBS (about 3 hours of increased good “on” time) in patients meeting DBS criteria, while newer infusion therapies may offer potential benefits through both pharmacokinetic effects from reducing peak-trough levels and a theoretical "deep priming" process that could reset hypersensitive dopamine receptors by providing continuous stimulation, though more research data is needed to confirm these hypothetical benefits.

Panelists discuss how a 66-year-old man with 8 years of Parkinson disease presenting with severe peak-dose dyskinesia affecting basic functions like eating and speaking, plus 4 hours of daily “off” time despite frequent dosing, represents a patient who should not have been allowed to progress to such advanced motor complications, emphasizing that the preferred approach is early intervention to treat motor fluctuations and dyskinesia as they develop rather than waiting until patients reach this severely impaired state with complex symptoms requiring more intensive management strategies.

Panelists discuss how treatment decisions for complex cases like the 66-year-old man with severe dyskinesia and 4 hours of daily “off” time require individualized approaches based on patient tolerance, with options including delayed-release/extended-release amantadine (starting at lower doses in older patients due to hallucination risk), extended-release carbidopa-levodopa formulations, infusion pumps for potential deep priming effects, or deep brain stimulation for patients seeking rapid improvement, emphasizing the importance of engaging patients in discussions about their patience for dose adjustments, risk tolerance for adverse effects, and desired timeline for symptom control to guide optimal treatment selection.