Dan Keller 00:08 Welcome to this episode of Substantial Matters: Life and Science of Parkinson's. I'm your host, Dan Keller, at the Parkinson's Foundation. We want all people with Parkinson's and their families to get the care and support they need. Better care starts with better research and leads to better lives. In this podcast series, we highlight the fruits of that research — the treatments and techniques that can help you live a better life now, as well as research that can bring a better tomorrow.
If you've had Parkinson's for a while, you probably know that it can be unpredictable. Symptoms can come and go, or get better and worse throughout the day, sometimes changing hour to hour or even minute to minute. These changes, called motor fluctuations by healthcare professionals, can be bothersome. But with a variety of modern medicines and appropriate dosing and timing, you can often control your symptoms. Teaming up with a good movement disorders specialist is key to managing your condition and living your best possible life.
At the recent Parkinson's Foundation Centers of Excellence Leadership Conference, I spoke with Irene Malaty, a movement disorders neurologist and the director of the Parkinson's Foundation Center of Excellence at the University of Florida in Gainesville. She told me how people with Parkinson's can work with their doctors to control motor fluctuations. What are they? What do people know about them?
Dr. Irene Malaty 01:43 Motor fluctuations are the symptoms related to movement in Parkinson's disease that change in relationship to the effects of medications. Oftentimes, people with Parkinson's — if they've had Parkinson's long enough and if they have enough symptoms — will experience a significant difference once their medication takes effect. We like to refer to that as feeling "on," as if their medicine is working: they can move more easily, and if they have tremor, the tremor may be less. Then, as the medication reaches its peak, sometimes people experience an overflow of movement that we call dyskinesia, which is an abnormal involuntary movement — a kind of wiggling movement. Then, as the medicine wears off at the end of a dose interval — meaning the time between one dose and the next — people can have a return of their symptoms, where they feel "off," or more stiff, or more shaky, or less able to move around. In early Parkinson's, it's really easy to take a few doses and have a really good, sustained, consistent benefit. But as people have it a little longer, the dependence on the medication is greater, and people can experience those ups and downs throughout the course of the day.
Dan Keller 03:00 So is that because early on they're still making a little bit of dopamine, and it kind of gives them coverage — but then they become really dependent on the medicine to supply that effect?
Dr. Irene Malaty Yes.
Dan Keller How do these fluctuations impact people?
Dr. Irene Malaty They may have too much movement at one point, and then can't move enough at another.
Dan Keller So how does this interfere with their daily life?
Dr. Irene Malaty 03:22 It can be very frustrating and impactful. When a person's medicine is working, they may be able to function quite well and do the things they enjoy doing. But when the dyskinesia comes, it can be mild — what we call non-troublesome — or it can be very aggravating, affecting their coordination and balance. And certainly, when the medicine wears off, some people may feel nearly paralyzed from doing the things they would like to be doing. So some people learn to adapt and plan their activities around their medication. For instance, someone who loves to golf may purposely time their medication so that it will be at its peak when they want to be out with their friends on the course. Or if people have social events, they may need to talk with their healthcare provider about what kinds of minor adjustments can be made to optimize their function during those times.
Dan Keller 04:15 When people are experiencing off periods, are there any shorter-term rescue medications that people use, or is it just a matter of taking your Sinemet or whatever — or you don't?
Dr. Irene Malaty 04:27 There are a lot of options, and a lot of factors go into deciding what the best medication-change strategy is. If off periods are rare, then we might use something like a rescue dose taken as needed. For some people, that could be as simple as an extra half pill or full pill of levodopa. For people who have more significant, sudden, and disabling offs, there are even injectable therapies — like something called apomorphine, known by the brand name Apokyn.
If these problems are happening consistently on a regular, daily basis, or often enough to disrupt quality of life, then it can be time to adjust the everyday pattern of medications. Sometimes, if the issue is only wearing off, a medicine can be added that extends the duration of benefit. Another option is to move doses a little closer together — instead of taking them only three times a day, it might need to be four times a day, or instead of every five hours, every four hours.
For some people, the bothersome part is the dyskinesias, or involuntary movements. In those cases, sometimes we add a medication called amantadine, which can help suppress those extra movements. Sometimes we have to reduce the amount of medicine per dose to try to avoid high peak levels in the body that can contribute to dyskinesia. Sometimes we have to remove add-on therapies and simplify the regimen. And sometimes we switch to more long-acting formulations that provide a slower, steadier release of medication.
We now have multiple formulations of levodopa. The medicine commonly known as Sinemet — carbidopa/levodopa — comes in a lot of different forms. One of them is Sinemet CR, which is a slower-release version. The newer one, called Rytary, has beads inside that dissolve at different times, providing partially more immediate and partially slower release, trying to find a middle ground. We also have an orally dissolving form for people who want to take something quickly without having to swallow a tablet with water — though regular carbidopa/levodopa can also be chewed. There are even long-acting forms of dopamine agonists, including oral forms of pramipexole and ropinirole, as well as the rotigotine patch, all of which are slower-release options.
I also want to mention another formulation I didn't name yet: Stalevo, which is carbidopa/levodopa with an additional medicine called entacapone. The goal is to slow down the metabolism of levodopa so it lasts a little longer. Some people find that it aggravates their dyskinesias, but others find it extends their benefit.
A lot of times, we have to look carefully at the timing of bothersome symptoms and determine what they are. Sometimes we even move on to thinking about surgical therapies. Surgical therapies for Parkinson's are not right for every single person, but they can be life-changing for the right person.
One of those is levodopa that is infused continuously over 16 hours through what's called a PEG-J tube — a small tube permanently inserted into the abdomen, where a pump can be attached in the morning and just let the levodopa run at a consistent level for 16 hours a day, then removed at night. The goal is to avoid the ups and downs by maintaining a steady, continuous rate. Sometimes those patients still take some oral medication as well.
The other surgical option is called Deep Brain Stimulation surgery. An electrode — what you might think of as a wire — is placed deep into the areas of the brain involved with Parkinson's and connected via a wire tunneled under the skin to a battery in the chest. Similar to a pacemaker for the heart, this is like a pacemaker for the brain. It uses electrical pulses to change the firing patterns in the brain in a way that helps improve Parkinson's symptoms. It can be an effective strategy for reducing dyskinesia and evening out the ups and downs — not necessarily doing dramatically better than the best that medication can achieve, but keeping things more consistent. It can also help tremor significantly, sometimes even beyond what medicine can do alone.
There are other surgical therapies as well, called lesions — small areas of targeted tissue destruction in the brain — but deep brain stimulation has the advantage of being programmable and adjustable. So there are lots of options that can be worked through to try to improve these fluctuations.
There's also one class of medicine I want to mention to be complete: selegiline, rasagiline, and a newer one that was recently approved — these are called monoamine oxidase inhibitors, or MAO-B inhibitors, and they also have a mild benefit of reducing off time.
Dan Keller 09:38 With all these options — you've laid out a lot — it sounds like the only way a movement disorder specialist is going to know what to move on to is if the patient reports how they're doing. So what should the patient be looking for? What should they be discussing with their doctor?
Dr. Irene Malaty 09:56 That's a very important question. First, I think it's important to make sure you're speaking the same language as your doctor, nurse practitioner, or ARNP — whatever provider you're seeing. For example, sometimes people use the word "tremor" because their body is moving in a way they don't want it to, but they might really be describing dyskinesia — a different kind of wiggling movement. So I always think it's important to clarify what we mean when we say "on," "off," or "tremor," and to describe those symptoms carefully.
Then, the critical thing is to look at timing. I ask people: what are the good times of day and the bad times of day? Can you tell when your medicine kicks in and when it wears off? Some people can tell me, "Half an hour before my pill is due, I don't need a clock — I know because I can't move." That's really useful information, because now I know the problem is duration of benefit. So I like to say: pay attention to what time you took your pill and what went wrong or right afterward, because knowing how well it worked and how long it lasted are probably the two most critical pieces of information for figuring out what needs to change.
Dan Keller 11:07 So how well do people do? If they're under good management and you've titrated the dosing and the timing — how is their quality of life?
Dr. Irene Malaty 11:21 I think people can live a good life, and they need a good doctor and good rehabilitation therapists by their side to help them navigate all of this. I sometimes tell my patients that Parkinson's is like a game where the rules keep changing. What works today isn't necessarily what's going to work in six months or twelve months. But sometimes we can do really simple things — like adding a helper medication or slightly adjusting the timing or dose — and really make a dramatic improvement in quality of life.
What I would say is: don't suffer through it. Talk to your doctor about what's happening, because a lot of times we can shift things in a way that really improves quality of life and keeps people doing the things they love to do.
Dan Keller 12:27 If you need to find a movement disorder specialist, call our helpline at 1-800-4PD-INFO. It is important to seek expert care. For more information on that, listen to Episode 2 of this podcast series: The Parkinson's Foundation's Role in Setting Standards of Care. It is also important to find a doctor that is the best fit for you — someone you can trust. Be sure to keep open the lines of communication so your doctor always knows your top concerns.
If you want to leave feedback or comments on this podcast or any other subject, you can do so at parkinson.org/feedback. We'll respond to some questions in future episodes. At the Parkinson's Foundation, our mission is to help every person diagnosed with Parkinson's live the best possible life today. To that end, we'll be bringing you a new episode in this podcast series twice a month.
In our next podcast, we'll pick up with a discussion on new delivery methods for levodopa. Until then, for more information and resources, visit parkinson.org or call our toll-free helpline at 1-800-4PD-INFO — that's 1-800-473-4636.
There are a couple of resources you may find particularly useful after today's conversation with Dr. Malaty. One is our free book, Managing Parkinson's Mid-Stride, available in the e-store on our website. Another is our video series with Dr. Malaty on motor fluctuations. Check it out at parkinson.org/videos.
Thank you for listening.
