Rajesh Pahwa, MD; Laxman Bahroo, DO; and Robert A. Hauser, MD, MBA, examine the impact of OFF episodes on patients and their families’ quality of life and discuss goals of therapy for Parkinson Disease.
Stuart Isaacson, MD: Raj, we've spoken about this idea of medications that can extend the duration of benefit of doses of medication and those that might be more rapid in their onset. How much does this distinction between the central causes of OFF, this loss of striatal nerve terminals, and the peripheral variability of levodopa delivery and absorption? How much do you try to distinguish that in your patients, and how much does that direct you toward a particular type of therapy?
Rajesh Pahwa, MD: In some patients, this is a very important distinction to make. That's why I said when you ask a patient how they are first thing when they wake up, if the patient says, “Oh, I'm not doing well. I'm slow at that time;” they take a pill, and it takes them an hour for it to kick in or it may not even kick on until the second dose of the day, that would suggest to me that some of the peripheral mechanisms are playing a role in addition to the central mechanism. If I can get something to them faster, bypassing the gut, it is going to make a big difference for them. In this case, adding an adjunctive therapy might be helpful, but to me, that means that I need to give them something to get the medicine to the brain faster for those purposes. On the other hand, if I have a patient who tells me that they're having end-of-dose wearing off, maybe it's not as regular as it should be with each dose—1 dose lasting 3 hours, 1 dose lasting 3.5 hours. Adding an adjunctive therapy for them would be a better idea for me. Of course, to me, on-demand therapy could be used at any time, but trying to find a distinction as to when to use an adjunctive therapy versus when to try to look at and see how I can bypass the gut to get to the blood faster, it does help me make certain decisions on what medication to use.
Stuart Isaacson, MD: Laxman, how do you assess the impact of OFF episodes on your patients, and specifically, do you ever assess the impact differently when you're looking at the impact of a wearing-off or the impact of a delayed on or a dose failure?
Laxman Bahroo, DO: Absolutely. The first thing is to always ask patients when they have these OFFs, what can they not do? How does the OFF impact your day? The answers can vary based on what state they're in, how mild the OFF is. Many times, patients will tell me if they're having a mild OFF, they'll just wait out the OFF in many ways. Sometimes they'll say, “No, the OFF does impact me. I can't get to work on time because my morning dose doesn't kick in quickly enough” or “I can't get home because I have to drive home, and around 3:00, 4:00 is when I hit that bottom point and I really need to be on at that time.” The impact varies based on, well, how severe the symptoms are, how predictable or unpredictable symptoms are, and of course, how active they are. A 75-year-old sedentary individual may be less impacted by their OFFs even though they may be more moderate, and a 45-year-old gentleman may be impacted much more by their OFFs even though they're milder because they're much more active. You must assess the OFFs based on what the patients are telling you; based on their state of life, their level of activity, the frequency of OFFs, the severity of OFFs, and how much they're impacted by them. Sometimes the dose delay is probably the worst in many ways because people are more focused on noticing that their symptoms will reemerge as they're coming close to the dose, but then they'll take a dose, and they'll feel it never kicked in. They feel that betrayed feeling that the dose never worked, and how could it just not work and kick in? Sometimes they'll say, “I took a dose, and it had a paradoxical reaction. It turned me OFF.” No, that doesn't make sense. That means they were ON until the dose. They took that dose at 11:00 and then by 12:00 they were OFF. The previous dose had worked all the way up to that point, even past it. The next dose never took the baton and ran with it, so hence they have an OFF episode after a dose, but they think that the dose didn't kick in. It's that the dose really turned them OFF. The medication isn't working. Be aware of those folks that come in and tell you medication suddenly isn't working. They're trying to describe an OFF in maybe different wording.
Rajesh Pahwa, MD: One other thing I look at is if my patient calls me before their visit and says, “My medicine is falling 30-minute short or 45-minute short.” Well, it is impacting them. Otherwise, they would not be calling me and would wait until they came to the visit to discuss that.
Laxman Bahroo, DO: In some ways, virtual visits have been helpful for us for those patients because in the past when patients were experiencing OFFs during your appointment times, they'd simply call and cancel their appointment. Now they'll simply call us and say, “Can we move to virtual?” I say, sure. Many times, when I get on the virtual with those individuals, I realize they're OFF. They've had an OFF, they just didn't quite describe it that way, but they can't move or they can't come to the appointment. Whereas in the past they would've canceled it. We would've thought nothing more of it and seen them a few weeks later or whenever they were able to schedule again.
Stuart Isaacson, MD: Bob, it sounds like OFFs are common and can be problematic and impact our patients. How do you set the goals of your Parkinson treatment, though? Is the goal to have no OFFs? Is the goal to have good ON as you defined it earlier? How do you set your goals for patients? It's individualized, but how do you consider differences and then how some patients might settle for some OFF and others won't?
Robert A. Hauser, MD, MBA: This is an individual question regarding physician and patient. I'll just tell you that in my mind, I'm trying to think about having good function through the day. It does differ from patient to patient. Raj started to hit on it somewhat regarding it varies by age and it varies by what kind of activities the patients are engaged in. Somebody who is trying to maintain employment as a, let's say, surgeon is different than someone who is retired. The key is just talking to the patient and understanding what's happening to them through the day and understanding what kind of function they need. Again, if they need that high function, they need to be at that top level all through the day. That's got to be your goal. Even a little bit of dyskinesia, a little bit of OFF can be quite a problem for that kind of person. Someone who is older and is retired, if they say, “Well, it starts to wear off 20 minutes before the next dose kicks in and it's not that bad. I get a little slower.” To that person I may say, OK, if you're OK with it, I'm OK with it. I will add 1 other thing, which is, I often do turn to the care partner and ask, how do you describe it? You tell me,” because sometimes you do get a different perspective from the care partner. If they say, “Oh my goodness, he gets really slow, and he can't get out of his chair.” Then I'll take a different perspective on it. It is nice to get that opinion, but I do take a different approach depending on where the patient is in their life and their activities.
Transcript Edited for Clarity