Shifting the Paradigm to On-Demand Therapies in PD

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Fernando L. Pagan, MD: Off episodes are usually managed by giving more carbidopa-levodopa: a higher dose or more frequently. We can also add other classes of medications like dopamine agonists, MAO-B inhibitors, and CMOT chain inhibitors. Here, we have a change in the way we’ve been doing things, so one of the things that is now available to us is that we have more accessibility to on-demand therapies. We have injectables that can potentially break this off episode.

We also have, now, inhaled levodopa that can also break this off episode, and we may have other treatments for on-demand therapy. We’re changing the way we practice. Traditionally, we would just always add more medicine, and that may not address all the off episodes that our patients have. For Parkinson’s disease, as it progresses, rational polypharmacy is the mainstay, so we’re going to use a cocktail of medications to reduce the off time and these off episodes.

Even with adding more medicines, our patients may still experience these off episodes, so it’s good to have an on-demand therapy. This is where we’re shifting the way we treat movement disorders, and as I said earlier, we can think about how our colleagues in headaches do it.

When I think about an on-demand therapy, I look at the patient’s ability to carry out the procedures necessary to administer the medication.

Let’s take a look at some of the on-demand therapies. The first on-demand therapy that was approved in the United States was an injectable apomorphine, and it is a very effective medication. This medication, in my experience, does require a caregiver to help the patient put the apparatus together to be able to give the medication. Apomorphine is a significantly effective medication to be able to get the person from an off state back to an on state. This is a medicine that often comes to mind when you’re seeing somebody having a lot of off episodes.

However, the inhaled levodopa, in the clinical trials, 99.8% of patients were able to do that themselves and delivered the inhalation powder effectively in the clinical trials. It’s a little easier to use than the injectable. I’d take a look at the patients and offer the patients this: would they like an injectable or would they like an inhalation powder? It’s about looking at the patient, but it’s important for us, as movement disorder physicians, to be thinking about using these on-demand therapies to get better control of these off episodes. Traditionally, we just give more plain oral carbidopa-levodopa, and as I explained earlier, a lot of the time, it’s a gastrointestinal problem. Bypassing the gastrointestinal system is extremely important, so inhaling or injecting, which we currently have available to us, are ideal ways of being able to treat patients when they’re having these off episodes.


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