Unmet Needs and Improving Diagnosis of Dyskinesia in Parkinson Disease


The expert panel reviews unmet needs in treatment and management of dyskinesia and shares advice for physicians treating patients with Parkinson disease.

Daniel E. Kremens, MD, JD: What are the unmet needs in the management of dyskinesia in Parkinson disease? One great unmet need is that our understanding of the basic science of levodopa-induced dyskinesia is still in the shadows. That makes the development of newer drugs challenging. Bill, what thoughts do you have on that?

William G. Ondo, MD: We have only 3 tried-and-true strategies to reduce the dopaminergic medication to minimize the peak dose effect: the surgical methods, the deep-brain stimulation and lesioning technologies, and then amantadine. It would be nice to have more options. We can always hope to do better.

Daniel E. Kremens, MD, JD: Anything else?

Robert A. Hauser, MD, MBA: Along those lines, we don’t understand the mechanisms by which levodopa induces dyskinesia. We talked about how pulsatile stimulation probably plays a role, but I believe it’s more than just that. Our first need is a medication that will vastly improve Parkinsonian features and doesn’t cause dyskinesia. That would be great. That’s a huge unmet need. There’s been some suggestion that D1 agonists could play that role; we’ll see. That would be important, but maybe other medications in the future could do that. I don’t know.

Daniel E. Kremens, MD, JD: Any thoughts on what physicians can do to improve the diagnosis and treatment of dyskinesia?

Fernando Pagan, MD: The first thing is education: learning how to diagnose the dyskinesia, how to talk with your patients about motor fluctuation, what ON is, what OFF is, what’s tremor, and what’s dyskinesia. When you’re taking care of patients with Parkinson disease, having that fundamental understanding is very important. Finally, understanding that the different formulations of amantadine out there are a little different. We have the best clinical research data is with the amantadine DR/ER. An unmet need is a head-to-head trial with amantadine IR [immediate release] and amantadine DR/ER. I wish that would be done. I don’t know if anybody would ever support that type of study because many feel they’re the same drug. But when you change the pharmacokinetic profile of a drug, you see different clinical responses. We see that with levodopa. If you change a pharmacokinetic profile of carbidopa-levodopa IR compared with the extended-release formulations, you see different clinical responses. We have clinical research proving that. It’s important to understand that when you change a drug like amantadine into a DR/ER formulation, that’s not the same thing that’s available within amantadine IR.

Daniel E. Kremens, MD, JD: As you point out, Fernando, in the carbidopa-levodopa studies, we have head-to-head data comparing the IR preparations with the extended release, and we don’t have that in the amantadine world.

Rajesh Pahwa, MD: The other thing we need to realize is that as physicians, we’re so concerned about the dyskinesia that we often undertreat our patients. Some of it may be driven by the patients too, but our goal should be to give the patient enough levodopa and enough Parkinson medicine so they can function. Our worry shouldn’t be that this patient will develop dyskinesia. Our goal should be a drug that we can use, and if the drug doesn’t work, we have surgical options. Let’s keep the patient functional rather than trying to avoid the medicines due to fears of dyskinesia.

Daniel E. Kremens, MD, JD: I agree.

Robert A. Hauser, MD, MBA: Dan, I want to bring up the other answer to your question. We’re entering the era of objective sensors, wearables, and things that are placed in the room. If we’re going to be inundated with data, and we’re going to be picking up more slight and mild dyskinesia, and we’re going to have to deal with that. How much dyskinesia is too much dyskinesia? When do we treat? That feeds into the whole conversation we’ve been having.

Daniel E. Kremens, MD, JD: Any final advice for physicians who are treating patients with Parkinson disease and dyskinesia? We have a therapeutic bind when we see a patient who’s dyskinetic and experiencing an OFF episode. We have a way to address that therapeutic bind with a medication that has been proven in multiple double-blind placebo-controlled studies to be efficacious for OFF and for dyskinesia. It’s important for physicians to realize that once the patient gets the dyskinesia, it’s going to get worse; we have to address it. In the appropriate patient, we can addressing dyskinesia and OFF early. If we can do it with 1 medication, that’s helpful for patients. Any thoughts from the panel?

Fernando Pagan, MD: I agree. We’ve learned with treating the dyskinesia that a lot of our patients are also having OFF time. As soon as you start to see these motor fluctuations, use a once-a-day nightly medicine. That’s going to reduce OFF time and improve ON time without troublesome dyskinesia and reduce dyskinesia without changing the overall levodopa dose. This is something you have to try. You don’t always want to reduce the levodopa dose and increase disability and more OFF time for those patients; that’s the old-school way of thinking. Look at what we’ve learned through the clinical research trials. What Raj has been saying is correct: we want to keep our patients with as much ON time as possible. That’s what’s exciting about the clinical research. It teaches us how to use these drugs and how we can improve the quality of life of our patients.

Daniel E. Kremens, MD, JD: I’d like to thank all of you for joining us for our program. I thank our panel for a robust discussion. Thank you very much.

Transcript Edited for Clarity

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