Stuart Isaacson, MD: How much attention should we pay to OFF episodes? Is the successful goal of treating Parkinson to have no OFF? Well, how much OFF is tolerable? How do we judge?
Rajesh Pahwa, MD: I think you’re right. The ideal goal should be to have no OFF periods. It’s like asking me or you, “Well, during the day, would be it okay if you couldn’t function well for an hour?” We’re all going to say, “No, absolutely not. I want to function all day long.” And especially if I told you the hour could happen sometime during the day, but I can’t tell you when it’s going to happen. So to me, yes, the goal should be that they don’t have any OFF periods, but I know that’s a very high bar.
Peter LeWitt, MD, M.Med.Sc: One of the interesting things as you look at the continuous intestinal infusion of levodopa, and this is the published double-blind study with placebo control, is that patients improved with continuous levodopa delivery through their gastrointestinal tract and presumably to the brain. And yet, all OFF time on the home diaries over the 3-month trial didn’t go away. So we may not have, with levodopa, even given in a continuous manner, the whole answer to this problem.
Rajesh Pahwa, MD: But the thing could be their severity of OFF was better, and that’s why they felt better and were not that concerned with the OFF. We also know that with deep brain stimulation, patients are not as OFF and they function much better. So they are not that concerned about it. That’s why I go back to it’s the severity of OFF, right? If I’m sleepy for an hour in the afternoon every day, I’m going to say, “OK, whatever, I can have a cup of coffee and fight through that sleepiness.” I think it is the same thing with patients. If they have a little bit of OFF, they’re like, “OK, I can function. I don’t want another pill. I don’t want to add a pill burden,” or whatever it might be. But if it is impairing them, then we need to make sure those OFF periods that cause functional impairment are not happening.
Stuart Isaacson, MD: Sometimes I try to give an analogy to patients to try to gauge the severity by thinking about driving to the store. If the roads are open, you get there easily. But now you have some traffic and it takes you longer. And this may be a degree of slowness. Sometimes you get into a traffic jam and you don’t move at all, and you’re completely OFF. So understanding that there could be degrees of how you respond to medicine and how you are turning OFF, or partially OFF, or partially ON may help patients understand that maybe we can raise the bar and raise the amount of….
Peter LeWitt, MD, M.Med.Sc: And there’s a cost-benefit ratio. You may have to keep up with a more complicated schedule. You may have to anticipate an adverse effect like dyskinesia if you’re loading up on extra medicine. But if your goal is to get to that store and not miss the sale…. That’s an important part of patient decision making. How much do they want to be involved in giving you feedback? How much do they want their family to be observers of their life, as personal as it may be for them? The decision making for how to use medications is a complex human interaction.
I find my study coordinators in research studies, or the nurse practitioner working with me doing a much better job in many instances than I can do because getting down to the nitty-gritty human level of how you lead your life vis-a-vis these medications is an art that, with the 5-minute office visit the clinician carries out, may not be ideal. So we have to use whatever tools we can. I don’t think home diaries are the answer, but I’d be interested in how everyone views the feedback system—if you have electronic feedback through MyChart [patient portal] or something like, or if you welcome phone calls, or if you want patients to write out anecdotal experiences of weddings that went well because they did it one way? I think that’s an important part of documenting and planning for patient care.
Stuart Isaacson, MD: It really shows the value of shared clinical decision making. While sometimes it’s hard to share, or there’s not enough time to share fully, patients have to be involved in this decision making. We can’t always judge, by knowing OFF, whether OFF needs to be treated for that patient.
Rajesh Pahwa, MD: But the challenge with what you are describing is physicians out there don’t have time. Having electronic communication every other day, a lot of time comes into play. And this is not all reimbursable. That is basically time a physician is spending. I don’t think we should overlook that part, like I mentioned earlier, that treatment of OFF is more expensive, from both the patient and physician standpoint. And we’ve got to come up with easier ways for it. I think rather than an email or electronic communication, I think variables are what’s going to be there in the future. For instance, a patient comes in and we have like an EKG [electrocardiogram] or report about how their bradykinesia was, how their dyskinesia was, that we will assess, and can make a decision based on that rather than having frequent communication.
Peter LeWitt, MD, M.Med.Sc: Right, I agree. What comes back is often unfiltered. It’s often general practice, people are talking about the constipation and other things because you’ve shown an interest in them. It does foster a notion of, “You’re now my general care physician,” or, “You can hear about all of the problems in my life.” So we have to walk that line. We want to continue to be practicing neurology in this context. I’m enamored with wearables. I just hope that they will have a practical impact in decision making, rather than just being a research tool.
Daniel E. Kremens, MD, JD: And I think another important thing is that, ultimately, we have to set realistic expectations with our patients as well. In a minute, I’m going to shift us to a discussion of the management of these patients. But I think even with optimal management, and you’re talking about the road analogy, Stu, well, sometimes the road is closed, right? There are issues with the blood-brain barrier that need to be addressed with Parkinson. So even with the best therapies, optimized medicine, some patients are still going to experience these episodes.