Current Series: Managing OFF Episodes in Parkinson Disease

Stuart Isaacson, MD: Do you think that a non-oral on-demand therapy, whether it’s subcutaneous, mucosal, inhaled, should be given to patients when the oral levodopa takes longer than 20 minutes, or longer than 30 minutes? How can general practitioners think about, “When do I give an on-demand non-oral therapy to my patient?”

Rajesh Pahwa, MD: I look at it as 30 minutes, and don’t ask me how I came up with the 30 minutes. Some of it is based on the fact that we have patients who say, “Oh, I take a pill and it works within 15, 20 minutes.” So to me, 30 minutes is a pretty good time. Looking at your study, where patients in the morning were ON in an average of 45 minutes, isn’t it correct, that they were taking for the morning medication to work? To me, 30 minutes seems like a reasonable time period on it.

Peter LeWitt, MD, M.Med.Sc: You could also frame it in, what are the consequences if you have an episode where you don’t get ON? You’re driving your car. You’re at work and experience embarrassment of something having to do with the perception of your capabilities. Having no episodes of OFF because you know you have a way to deal with that is another axis of thinking on this.

Daniel E. Kremens, MD, JD: This is truly, you’ve seen 1 case of Parkinson disease, you’ve seen 1 case, right? Every patient is different. If I had a patient who was taking levodopa 3 times a day and was generally doing well but was occasionally having an unpredictable OFF, I think that would be a patient who would be ideal to try inhaled levodopa. You don’t have to increase the burden of having to take the levodopa 4 times a day. You can give them an on-demand therapy that is relatively socially acceptable. People find inhalers, using them in public is not a big deal for them.

I think if I had a patient who was, in general, doing well with levodopa 3 times a day but was having difficulty getting to work in the morning because they woke up in a real OFF state, I think that would be an ideal patient to think about subcutaneous apomorphine for. We have the data that showed that can be a very effective therapy for those people to allow them to get on with their day and work. I really think you have to look at that patient and how, as Peter said, it’s impacting that person’s life—what the consequences are—and tailor the therapy to them.

Stuart Isaacson, MD: It may not just be how long it takes, but is it once a day, once a week, once a month, or only special occasions like a wedding or going to Disney World with their grandchildren?

Rajesh Pahwa, MD: Or on the other side, 5 times a day.

Stuart Isaacson, MD: But how do you decide? If the patient has an OFF episode once a month, would you give them an on-demand, non-oral therapy?

Peter LeWitt, MD, M.Med.Sc: If the consequence is that they’re not leaving their home because of that fear of it really happening once a month, but the perception that it might happen any time. I can imagine that at least putting that information in front of the patient—that you don’t have to stay holed up or retire early, and that there isn’t really a safety issue in your life if you have this EpiPen for Parkinsonism—that’s the way to couch it. I think the average person who gets it prescribed uses it regularly. Those who don’t use it once a month at least obviously drop off from therapy. They may have tried it.

But at least it gives them confidence for their future. If they go to a support group meeting and hear all of the people who are fluctuating and having hours of OFF time, they know that isn’t in their future if they take advantage of these therapies; and especially with apomorphine as a therapy that overrides OFF time that can occur even with continuous infusions. Some patients who are on Duopa infusion are using apomorphine because levodopa can shut down on them for who knows why.