When to Use On-Demand Therapies in Parkinson’s Disease

EP: 1.OFF Episodes in Parkinson’s Disease

EP: 2.Parkinson’s Disease: Why do OFF Episodes Occur?

EP: 3.Impact of Parkinson’s Disease OFF Episodes on Quality of Life

EP: 4.Expected and Unexpected OFF Episodes in Parkinson’s Disease

EP: 5.Parkinson’s Disease: Evaluating Patients for OFF Episodes

EP: 6.Motor and Non-Motor Symptoms in Parkinson’s Disease

EP: 7.The Relationship Between the Gut and Parkinson’s Disease

EP: 8.Important Attributes of On-Demand Therapies for Parkinson’s Disease

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EP: 9.When to Use On-Demand Therapies in Parkinson’s Disease

EP: 10.Levodopa Inhalation Powder for Parkinson’s Disease

EP: 11.Apomorphine Subcutaneous Injections for Parkinson’s Disease

EP: 12.Side Effects of Apomorphine Usage in Parkinson’s Disease

EP: 13.Sublingual Apomorphine for Parkinson’s Disease

EP: 14.Parkinson’s Disease: Advice for Community Neurologists

Stuart Isaacson, MD: When we start thinking about OFF episodes and treating them with on-demand therapies, sometimes we think about the morning OFF as a place where we can begin these things. But how long do you wait? How many things do you try between long-acting 24-hour dopamine agonists and MAO [monoamine oxidase] inhibitors and increasing the doses of levodopa? When do you consider adding an on-demand therapy to manage a patient’s morning OFF episode?

William G. Ondo, MD: Our goal in Parkinson disease is achieving complete ON time, during the day and during sleep, therefore, my patient wakes up ON. And as soon as patients have motor fluctuation, I want to touch on overall OFF time even before we get to the morning OFF time. Every single patient with motor fluctuation deserves that on-demand therapy.

As soon as my patient is fluctuating, I oblige myself to explain what on-demand therapy is, and I tell them about the pros and cons of each one. I always use this analogy that they are exactly like a patient with migraine. Patients with migraine, regardless of whether the headaches are under control, they are carrying over the counter headache medication. On-demand medication has to be carried by our patients; when to use it, it’s up to them after they have a good understanding about how they respond to their medication. That’s a general statement about mortal fluctuation and OFF time.

When it gets to the morning OFF, there is no difference when it comes to the treatment. I do my best to keep my patients ON. If they get a good sleep, there’s a chance that they’ll basically wake up in ON condition. It doesn’t work all the time. I try to give them long-acting levodopa when they go to bed, so therefore maybe they can wake up ON. But several times we fail at that point. When they are OFF in the morning or any other time, that’s the time when I consider using one of the on-demand therapies.

Stuart Isaacson, MD: Dan, what’s your rationale for using an on-demand therapy, and when do you begin it for morning OFF?

Daniel E. Kremens, MD, JD: I tend to be a relatively early adapter. Once the patient is having these difficulties, I don’t think that taking another pill is going to solve it due to gut problems. And I think that they really need to start considering on-demand therapies, particularly in the morning because in the morning they’ve got an empty stomach, right? So presumably the dietary protein is not a big issue there, and it really is purely the gastroparesis and the slowing. I’m relatively aggressive about encouraging the patient to consider an on-demand therapy so they can get their day started and get on with things.

A lot of times patients with Parkinson disease sort of start to accept a quality of life that many of us wouldn’t feel is acceptable because it’s an insidious disease. It comes on slowly. Michael J. Fox described it as the gift that keeps on taking, and that’s a pretty accurate description of it. We need to be aggressive to help our patients maintain the best quality of life that they can have.

Stuart Isaacson, MD: When patients are taking carbidopa/levodopa, and they may be using this alone as monotherapy and then we may increase it or adjust the timing. Do you think about these on-demand therapies even before other adjunctive extender type of medications? Or do you think that you have to try other classes first before you go to an on-demand therapy?

Laxman Bahroo, DO: No. I like to think of them earlier, especially if they’re having what I call unpredictable ones or these one-offs, like, “I start with OFF in the morning, and the rest of my day I’m pretty good unless I miss a dose, or I’ve taken it too close to food.” I say, “That can be fixed. You need to take doses on time, and take them apart from food.” If that’s not a problem, you still have this problem in the morning. If they’re having these one-off problems or there’s no pattern to them, I often will tell them, “It’s very easy for me to tell you, take more levodopa, or just take it more frequently. Or just add an adjunct. Understandably, if you’re having OFF at 8 o’clock in the morning, and then another day you’re having OFF at 12 o’clock, another day you’re having OFF at 8 and 5 or some other time, there’s no pattern to this. I can’t give you a pill that can kick in only at this time and not affect the rest of the day, and vice versa.”

We need to be able to solve these issues. The way I liken it to my patients in an analogy is, “Imagine you’re driving a car and you hit a pothole. You’ll hit potholes at different times and the key is to fix potholes, not to build you a whole other road. By adding adjuvants, we’re kind of widening the road, but the road still has potholes in it. Fix the potholes, and that’s how we fix the potholes, with on-demand therapy.”

Khashayar Dashtipor, MD: As soon as you start your add-on therapy, you offer them on-demand therapy at the same time, correct?

Laxman Bahroo, DO: It depends. Let’s say I have somebody who is on levodopa only. In theory, most patients of mine may be on 1 add-on therapy because they may have started it first, or we may have added it when they would have experienced some end of dose wearing OFF. Let’s say they’re having mornings OFFs twice a week, and they’re having some other OFFs somewhere in the middle of the day. There are 2 different patterns to this, or maybe there’s no pattern to this. Rather than adding another adjunct of medication that they would have to take once a day every day that may or may not fix this, I would rather just add an on-demand medication here that they can take as needed. If they don’t need it, they don’t need it. They might only use it 3 times a week, or maybe 4 times a week.

Khashayar Dashtipor, MD: My philosophy is, as soon as you need to add another adjunct therapy, that’s the time when you have to introduce your patients to on-demand therapy. As soon as patients start to show motor fluctuation, they’re going to continue it because that motor fluctuation is unpredictable and each OFF time or ON time are not the same. A patient can say they are ON, but they are not fully ON, or they have delayed ON. Therefore, when a patient gets to the point that you’re thinking about an add-on, at the same time you have to introduce them to on-demand therapy as well.

Stuart Isaacson, MD: What do you think about this idea that when patients have OFF and we’re thinking about adjusting levodopa or adding an adjunctive medicine, that we should also offer an on-demand therapy to treat their OFF while we’re attempting to lessen their overall OFF time?

William G. Ondo, MD: It’s a case-by-case basis. I wouldn’t be quite so aggressive as Dash. I do think there are times with all of the options we have, including long-acting levodopa, that you can for at least a while get no OFF time. So that being said, there’s really not that much downside from a purely medical standpoint to using as-needed therapies like levodopa and apomorphine. These drugs have been around for a long time, so we’re fairly comfortable with using them.

If it is some modest predictable OFF time, I’m not sure if I would use them necessarily in the first line. If it’s unpredictable, then they certainly come up to first-line therapy for that. Otherwise, it’s kind of a case-by-case basis, depending on the needs of the patient.

Stuart Isaacson, MD: Thank you all for joining me and for watching this NeurologyLive® Peer Exchange. I hope you enjoyed the content. Please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.