On-Demand Therapies to Manage OFF Episodes in Parkinson Disease


Laxman Bahroo, DO, and Sanjay Iyer, MD, share considerations regarding the optimization of treatment selection and the addition of on-demand therapies to manage OFF episodes in Parkinson disease.

Sanjay Iyer, MD: What do you think is important to think through as we’re talking about on-demand therapy now? What is the ideal on-demand therapy, and what does it look like? And what’s important for patients to understand in terms of how to use them?

Laxman Bahroo, DO: Let’s talk about using them. Your message was empowerment. Patients must be empowered to understand their symptoms. If they understand their symptoms, they understand how it impacts their day-to-day functioning. If they do that, then they’re more likely to buy into the ability to correct them. If they don’t understand them and don’t feel like this is necessary to be treated, they’re not going to want to treat it, and they’ll just live the way they are. They may come to your visit, talk a about this, but do nothing about it. Empowerment is important in the sense of, this is the OFF episode, this is how it’s impairing you, this is what you can do about it. Is it important? Are you willing to treat this, in that sense? That’s the first step.

What is the perfect on-demand therapy? This will be an interesting discussion. Something that’s easy to use, that’s No. 1, because patients are using it. No. 2, it has to be quick because remember you’re already in an OFF. You want to get out of that OFF as quickly as possible, so the rapidness of it. It has to be potent enough to take the OFF to an ON. It needs to be easy to use, I would say rapid in terms of reversing this. I would say probably the next one would be it has to be potent to take you from a full OFF or to arrest the fall, and then reverse it. And it must be consistent. In other words, you must consistently get the same response with using it. If I had to pick one more, if you were talking about ideal, portability, it must be portable. In other words, if I don’t want to have it at home, and I don’t have it with me because it’s too clunky to carry, so the portability of it.

Sanjay Iyer, MD: That’s a great point. When you think through your patients and what their other symptoms are, and whether they have orthostatic hypotension already, or whether they’re chronically nauseated patients already, what are the things you think through in deciding which on-demand therapy might be the right fit for this individual?

Laxman Bahroo, DO: You brought them all up. If you have a lot of nausea, I tend to steer toward more toward inhaled levodopa in that sense and say, we have inhaled levodopa. But then I must caution at that point when I say inhaled levodopa is a good option, and say, well, how’s your lung function? Are you a smoker? Do you have COPD [chronic obstruction pulmonary disease]? And keep in mind, this is also the population that has a much higher pack-year history than one generation younger than them. There may be concerns there about pulmonary function issues. I bring up the fact that we have this option; how’s your pulmonary function? That brings me to a go/no-go point. If they tell me they were diagnosed with COPD, they have asthma, they don’t have good lung function, I stop. I say, “Go to a pulmonologist, get this reevaluated, bring this up as an option so they are aware of it, because I would want them to weigh in on this.”

If not, then I lay out options and say, look, we have different options. We have an injectable option, a sublingual option, and an inhaled option. Now, how do we choose between the 3? I’m going to tell you, if patients were to choose, patients are going to choose noninjectables over injectables. And then they might say, “Well, I prefer to do this, or no, I know levodopa, it works. I’m tending toward inhaled levodopa.” Or, “No, no. This is a strip I put under my tongue, the sublingual apomorphine, I can do that much more easily rather than using a device.” But then the injectable, you might say, well, people are not going to use the injectable. People do use the injectable because in terms of potency, the injectable differentiates itself. The other 2 are wonderfully portable options as we talked about, there’s ease of use, which is one of the factors I brought up. But you may not necessarily have that reversal as rapidly, or you may not have as complete of a reversal. If you’re OFF already, a classic example, my patient wakes up at 3 PM. They went to take a nap at 1 PM, they were supposed to take their dose at 1 PM, they forgot to take their dose. They wake up at 3 PM and they’re fully OFF. They need to go from a full OFF to a full ON, and taking the tablet 2 hours late isn’t going to get them there that quickly. They need the ability to go from a full OFF, to a full ON, and maybe the injectable subcutaneous apomorphine will get them there in that sense. And maybe the other ones may not get them there as much.

You have to consider how bad are the OFFs, or how severe are they? What’s the urgency of treating them? In other words, I need to be fully ON in 15 minutes, or know, I’m starting to go OFF, maybe I should use this to bridge myself from this OFF to the next ON. And I’m not as deeply OFF, but I will be if I wait 45 minutes. I tend to use bridge vs rescue therapy. Rescues are almost always going to be injectable apomorphine. Bridges are going to be the sublingual apomorphine and the inhaled levodopa. Injectable apomorphine subcutaneous will also be a bridge as well, you can use this as both. I don’t mean to imply one or the other, but in that sense, it’s kind of what I call stratification of OFFs. You stratify the severity of it. Then some individuals might have less severe OFFs and more severe OFFs, but then you’ve got to treat the most excessive OFF to be able to successfully treat everything up to that point.

Sanjay Iyer, MD: What are your thoughts about the patients who have some cognitive impairment and maybe some hallucinations, yet they experience some deep OFFs? Do you do you have a preference in terms of leaning toward the levodopa vs the apomorphine products?

Laxman Bahroo, DO: There are challenges. There’s no good answer. I like the tough question because on one hand, I would say, you know what, levodopa might be a better option than a dopamine agonist. Apomorphine is different than the other dopamine agonists, it’s a D1, D2. We may not see as much hallucination as we would with our broad-spectrum pramipexole or…, which are D1 to D5. But the conservative treater in me, I might say, let me hedge toward the inhaled levodopa. Now here’s the problem. Those individuals may not be able to self-administer the inhaled levodopa because it requires them to open a device, couple and uncouple the device, insert a capsule, inhale, and repeat. That process may be cumbersome for them, while levodopa may be an option. In those individuals, I may steer toward a sublingual apomorphine, but I may titrate more slowly and gently. Those would be my go-to options. Similarly, if they have a caregiver, then I can consider talking about the subcutaneous apomorphine because they will need some help with this.

Sanjay Iyer, MD: It’s a great point, if you have a reliable caregiver, I tend to lean toward the injectable subcutaneous apomorphine. Even just the logistics of understanding how to properly inhale the levodopa can be tricky. Even for people with no cognitive impairment, the sublingual can be difficult to understand how long do I keep it in here? If they’re swallowing and there is saliva, they don’t quite understand it’s going to be deactivated. In that situation, again, if you have a good caregiver, I tend to lean toward the injectable.

Laxman Bahroo, DO: That’s a great point I didn’t bring up. If you swallow your sublingual dose, it is gone.

Transcript Edited for Clarity

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