Current Series: Managing Off Episodes In Parkinsons Disease

Stuart Isaacson, MD: Do you think a subcutaneous infusion will occur before the jejunal infusion, or even before DBS [deep brain stimulation] as they became more available with these....

Peter LeWitt, MD, M.Med.Sc: It makes sense to think of that as a staged kind of therapy. In Europe, the Netherlands, for example, where both are available, I asked that question to a practitioner who’s very much an expert in both, and he still flips a coin mentally to figure out which patient is going to do better on 1 drug or the other. There may be some pros and cons of each, but both are highly acceptable therapies, and in the European setting are routinely used.

Rajesh Pahwa, MD: But practically, think about it. If I was a patient and I was given an option of having a hole drilled in my stomach or belly to give me intrajejunal levodopa, or 2 holes in my brain to do deep brain stimulation, or do a subcutaneous infusion, I think all of us would pick a subcutaneous infusion first.

Peter LeWitt, MD, M.Med.Sc: Oh, I would agree.

Rajesh Pahwa, MD: Because you can try it for a period, whether it’s 4 weeks, whether it’s 6 weeks, whether it’s 8 weeks, and then, OK, you have tried, so to speak, a noninvasive therapy before you….

Peter LeWitt, MD, M.Med.Sc: Keep in mind that jejunal therapy can be achieved through the uncomfortable procedure of putting a nasogastric tube in. In the original study, that’s how we did it.

Rajesh Pahwa, MD: Right, but that’s not going to be long-term practical.

Peter LeWitt, MD, M.Med.Sc: That’s 1 day’s experience, at best, before it gets yanked.

Rajesh Pahwa, MD: Exactly. So to me, that definitely becomes something we would use before we go into intrajejunal and deep brain stimulation. And the thing is, the studies that you mentioned earlier have shown that we can reduce OFF time with the subcutaneous infusion. They have a lot of safety data from Europe demonstrating that it does work. The issue is going to be more around how much OFF time they have to have before we start using that therapy, rather than, should we be using that therapy?

Daniel E. Kremens, MD, JD: In my practice, I’m already using the available on-demand therapies often as a bridge before the more invasive therapies, such as deep brain stimulation or intrajejunal levodopa.

Stuart Isaacson, MD: We’ve always been interested in trying to find some therapy that can delay progression, or slow progression, or whatever neuroprotection means. But these infusion-based therapies may have some effect on plasticity. There have been some studies that suggest that taking an infusion-based continuous delivery may change the thresholds of things like dyskinesia.

Peter LeWitt, MD, M.Med.Sc: I’m also impressed with the fact of improving quality of nighttime experience, sleep can be helped by those who’ve used around-the-clock infusion therapies. One of the great disabilities of Parkinson, the impaired sleep, the disrupted thought process that goes on during sleep, might be helped greatly. And interestingly, evidence that even hallucinations, which you would think a potent dopaminergic agonist like apomorphine could make worse, has actually, in published data, shown to be improved with it. Maybe that pulsatility issue could also be the explanation?

Rajesh Pahwa, MD: And just like GI [gastrointestinal] issues, I think we have under discussed sleep issues in Parkinson. We think a patient taking the last dose at 6 in the evening and not taking a pill until 8 in the morning is fine, but a lot of them have issues that are often related to not being adequately treated at night.