Treatment of Dyskinesia in Patients with Parkinson’s Disease

EP: 1.Treatment Options for Parkinson Disease

EP: 2.Use of Parkinson Disease Treatments and Identification of OFF Episodes in Clinical Practice

EP: 3.Challenges With Parkinson Disease Treatments

EP: 4.Pathophysiology of Dyskinesia in Parkinson Disease

EP: 5.Risk Factors for Dyskinesia in Patients With Parkinson Disease

EP: 6.Diagnosis of Dyskinesia and Impact on Quality of Life of Patients With Parkinson Disease

EP: 7.Challenges in Balancing Treatment of OFF Episodes and Dyskinesia in Parkinson Disease

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EP: 8.Treatment of Dyskinesia in Patients with Parkinson’s Disease

EP: 9.Amantadine Formulations in Treatment of Dyskinesia in Parkinson Disease

EP: 10.Studies With Amantadine-DR/ER for Treatment of Dyskinesia

EP: 11.Amantadine DR/ER for Dyskinesia in Parkinson Disease: Safety Profile and Ideal Patient

EP: 12.Use of Other Amantadine Formulations in Parkinson Disease

EP: 13.Surgical Options and Emerging Treatments for Parkinson Disease

EP: 14.Unmet Needs and Improving Diagnosis of Dyskinesia in Parkinson Disease

Daniel E. Kremens, MD, JD: Let’s shift now to the discussion of how we treat dyskinesia in patients with Parkinson disease. We’ve identified that for many patients there is this push-me, pull-you therapeutic dilemma of treating OFF episodes is going to worsen dyskinesia, and treating dyskinesia potentially worsens OFF, and so we’re stuck with this challenge. Raj, why don’t you tell us a bit about what have been some of the approaches to treating dyskinesia, particularly historically how do we do it?

Rajesh Pahwa, MD: Like I mentioned earlier, just because there is dyskinesia does not mean we necessarily treat it. If a patient has very mild dyskinesia, we may say we’ll just watch what happens. The other thing is people often try to cut down their medicine, not thinking that this could result in more OFF. I think that’s one of the things people often go to, “Oh, let me cut down the levodopa because that’s what’s causing the dyskinesia.” People can do that, but the problem is they’re going to have more OFF. Similarly, they try to reduce the levodopa or add another medication. It’s like, “OK, I’m going to cut down the levodopa, but I’ll add a dopamine agonist.” Well, that could work in the short term, or it may not work at all because again, it comes down to the overall dopaminergic load. If you cut down levodopa and add a low dose of dopamine agonist, the patient’s going to more likely than not end up with OFF. So that becomes the other challenge. Bill brought up amantadine, which is so far the only medication that we have seen to help with dyskinesia. Especially amantadine-DR/ER [delayed release/extended release], which has the data that not only does it help with the dyskinesia, but also with the OFF periods patients are getting. If that doesn’t work, then at times we end up using deep brain stimulation, or we may even use some infusion, which has data that it may also help with dyskinesia. In general we are looking at getting to a point where whether we treat the dyskinesia, we need to make sure we don’t worsen the OFF rather than help the OFF and the dyskinesia together.

Daniel E. Kremens, MD, JD: As you mentioned, there are surgical options. Something we’re hoping becomes available in the next year or two is more continuous delivery of levodopa, more physiologic delivery of levodopa through pumps. It’s not the focus of today’s discussion, but we certainly have some data that pumps with prolonged use may reduce dyskinesia. We saw that even back in some old studies with lisuride, with dopamine agonists; there are some data with carbidopa/levodopa gel infusion. Those also have the potential to help us address dyskinesia in patients with Parkinson disease. We’ve all been dancing around and touching on this. Fernando, perhaps you’d like to tell us a bit about nondopaminergic adjunctive treatments available to treat dyskinesia in patients who are receiving levodopa-based therapies.

Fernando Pagan, MD: For nondopaminergic medications, these are some of our adjunctive medicines, and we try to keep the dopamine as continuous as possible, or keep it around a bit longer to try to prevent some of those fluctuations. We can sometimes do that by adding a COMT inhibitor, MAO-B inhibitors, and A2A inhibitors to try to enhance the action of the dopaminergic products that we may be using, like levodopa. Interestingly, you can also increase the dyskinesia, but sometimes these medicines also allow you to lower the overall levodopa dosing for those patients. Also using a dopamine agonist, for example, you can get by with less levodopa. So sometimes you can add the adjunctive medications, but when you’re treating patients who are having these motor fluctuations, both OFF and dyskinesia, nothing really has the data like our amantadine-DR/ER. With the EASE LID studies, that’s what has been a game changer in the clinics. But we do try to use these other adjunctive therapies for patients who are having these motor fluctuations.

Transcript Edited for Clarity