Dr William G. Ondo provides an overview of available treatments and pharmacokinetic properties of different drugs for Parkinson Disease.
Daniel E. Kremens, MD, JD: Hello and welcome to this NeurologyLive® Peer Exchange titled, “Management of Dyskinesia and Advances in Treatment of Parkinson Disease.” I’m your host, Dr Daniel Kremens, an associate professor of neurology and codirector of the Parkinson Disease and Movement Disorder Center, and vice chair for education at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania. Joining me today in this discussion are my colleagues, Dr Rajesh Pahwa is a professor of neurology and chief of the division of movement disorders and director of Parkinson’s Foundation Center of Excellence at the University of Kansas Medical Center in Kansas City, Kansas. Dr Robert Hauser is the director of the Parkinson’s Disease and Movement Disorder Center and professor of neurology at the University of South Florida Morsani College of Medicine in Tampa, Florida. Dr William Ondo is the director of the movement disorders clinic at Houston Methodist in Houston, Texas. And Dr Fernando Pagan is a professor and vice chairman of the department of neurology at MedStar Georgetown University Hospital in Washington, DC.
In today’s conversation, we will focus on diagnosis and treatment of dyskinesia in patients with Parkinson disease. We will discuss the importance of early diagnosis of dyskinesia, available treatment options for the management of dyskinesia, and future directions in dyskinesia and Parkinson disease management. Welcome everyone, and let’s get started. Why don’t we start with you, Dr Ondo, can you lead us off with talking about current treatments in Parkinson disease? Could you provide us with an overview of the treatment landscape in Parkinson disease, focusing a bit on pharmacokinetic properties of different formulations of levodopa/carbidopa and adjunctive treatments?
William G. Ondo, MD: Sure, thanks, Dan. We are fortunate to have several relatively effective medicines for Parkinson disease, although there’s still nothing that has been proven to slow disease or get at the underlying problem. Most of the treatments we have in one way or another increase dopaminergic tone. At the forefront of this for the last 5 decades has been levodopa, which is converted into dopamine in the body. You can’t take dopamine tablets because they wouldn’t be absorbed; they wouldn’t cross the blood-brain barrier. One of the problems with levodopa historically is that it has a very short half-life. Over the years there have been several different preparations to try to extend the duration, with extended-release pills and an immediate-release combination. Extended-release pills are now available, but even with that, it still can be problematic because it requires at least 3 times a day and sometimes it’s 5, 6, 7, 8 times a day dosing to keep these continuous dopaminergic levels.
There have been some other advances, such as duodenal pumps for levodopa, although it hasn’t been particularly popular. In the future there may be some subcutaneous pumps for levodopa as well. There have been several other pharmacologic strategies to try to prolong the effects of levodopa, for example, COMT inhibitors, opicapone and entacapone being the 2 that are widely available in the United States, prevent the metabolism of levodopa and can extend the effective duration that you get out of levodopa tablets. They are used only in conjunction with levodopa, never as monotherapy. MAO-B inhibitors have some independent, albeit modest, symptomatic improvement in Parkinson disease, but can also be used as adjunct therapy to levodopa to try to extend the duration of ON time you might achieve. Then you have a class of medicines called dopamine agonists, which are independent mimickers of dopamine, and they have advantages and disadvantages compared to levodopa. The main advantage being that they tend to have a longer duration of effect, however, the main disadvantage is that they tend to have somewhat more in the way of adverse events compared to pure levodopa therapy.
There have been one or two novel mechanisms including a drug called istradefylline, which has a novel mechanism, an adenosine A2A antagonist, and that seems to secondarily increase dopaminergic tone. We have several surgical procedures that have been used for Parkinson disease since the mid-1990s, and these tend to be reserved for patients who are fluctuating with more advanced motor symptoms, although not necessarily more advanced overall, because they don’t seem to help cognition, mood, balance and certain other aspects of Parkinson disease that advanced patients often suffer from. So we do have a fair armamentarium of dopaminergic therapies for Parkinson disease, plus amantadine, which we’ll be talking about more in detail when we discuss dyskinesia.
Rajesh Pahwa, MD: It’s interesting to see that even though we have all these adjunctive therapies, we can have a patient taking 1, 2, or an adjunctive therapy from all these different classes. On the other hand, we have patients who cannot tolerate any of the adjunctive therapies and just end up taking levodopa.
Daniel E. Kremens, MD, JD: One other class of adjunctive therapies that are indicated but we rarely use are some of the anticholinergics. I think in the modern armamentarium, particularly due to the adverse effect profile of these drugs, they’re rarely used. Maybe in some patients who have especially bad tremor, we might try some of them.
Transcript Edited for Clarity