Non-Motor and Motor OFF Symptoms in Parkinson Disease

Daniel E. Kremens, MD, JD: Are those non-motor OFFs, or are they simply just non-motor symptoms of Parkinson disease? And one of the things that I find really interesting, and I’d be fascinated to hear the panel’s opinion on this, is do you think there can be non-motor OFFs without motor OFFs?

Peter LeWitt, MD, M.Med.Sc: Yes.

Rajesh Pahwa, MD: Yes.

Jill M. Giordano Farmer, DO, MPH: Yes, absolutely.

Peter LeWitt, MD, M.Med.Sc: Definitely.

Rajesh Pahwa, MD: And I think at times, the non-motor symptom is the first symptom that may come on. If a patient takes their dose, they may never get that motor OFF because they have aborted, so to speak, their non-motor OFF.

Daniel E. Kremens, MD, JD: Right. The reason I bring that up is because I think people really have to understand that, oftentimes, non-motor symptoms are going to be the first symptoms of OFF that patients will report. So as physicians, we really have to be asking about this, or we might be missing a lot of that.

Stuart Isaacson, MD: We know that patients rate these non-motor symptoms as probably most deleterious to their quality of life and their daily activities when we ask them in different types of surveys.

Peter LeWitt, MD, M.Med.Sc: I also have the experience of patients who intentionally take extra medication in situations where their mental acuity is needed, especially at the price of having dyskinesia. In fact, many patients are very tolerant of mild dyskinesias because there’s something extra that you get from the medication—a mild stimulant effect, or more alertness. So we have to be in tune to the fact that the analogy of improving motor symptoms, which has a threshold effect at a certain blood level, isn’t necessarily the best dose effect for the mind to work best. There’s more research needed on this topic, and it also may be an argument why more continuous therapies that don’t have fluctuations, don’t have the withdrawal of this psychic enhancing effect. I think many patients have discovered this on their own.

Jill M. Giordano Farmer, DO, MPH: I think that’s sort of exposed in patients when they come in terribly dyskinetic, but they tell you they feel OFF.

Daniel E. Kremens, MD, JD: Right.

Peter LeWitt, MD, M.Med.Sc: Or they feel great despite the fact that they look like a mess, and their family says, “Well, wait a minute, something’s wrong here.” But, yes, the overuse of levodopa is of concern because it’s not a drug of abuse, obviously, but many patients are taking far too much. But there’s a reason for that, and perhaps we have something to learn of the role of non-pulsatile therapies to ameliorate this withdrawal and feeling bad psychically in gaps that might not translate in terms of motor OFF.

Rajesh Pahwa, MD: But in general, more patients are undertreated than overtreated.

Daniel E. Kremens, MD, JD: And I think the overtreated patients are often the patients demanding that treatment, typically. I think most physicians tend to undertreat their Parkinson patients. But then, you occasionally have a young, typically male patient who engages in this dopamine dysregulation syndrome, demanding large amounts of dopamine despite the fact that they’re clearly not OFF when we see them in the office. They say, “Doctor, I’m so OFF,” when they’re wildly dyskinetic.

Rajesh Pahwa, MD: And that’s why, Peter, bringing up that issue that most of our patients would rather be dyskinetic, or slightly dyskinetic than OFF. Then are we, as physicians, undertreating them because we are so worried about the dyskinesia? We should also be helping their OFF, because OFF can be worse than their dyskinesia.