Educating Patients on OFF Symptoms in Parkinson Disease

Daniel E. Kremens, MD, JD: That brings up the natural point. We’ve talked about patients are experiencing this. But what we haven’t talked about is, how do we ask patients about this, and how do we educate patients about OFF? And OFF is so much more than just tremor re-emergence, right? Jill, how do you discuss this with patients?

Jill M. Giordano Farmer, DO, MPH: As we were saying, it takes a conversation and a dialogue. You have to figure out the vocabulary of what your patients are using to describe a symptom and what we’ve been taught to use as the term to describe the symptom.

The easiest way that I try to approach it is to get a general idea of, can they tell what symptoms are improved when their medications are working well for them? And then I’ll ask them what those symptoms are. And then whatever they’re describing, I’ll say, “Well, do you notice if these symptoms that you’ve described come back?” Typically, you think of the motor symptoms in that regard—tremor, slowness, stiffness, a feeling of unsteadiness or imbalance. But it is not just the motor symptoms. Those are always the most obvious ones that people can talk about. And then if that’s all that they’re describing to me, I’ll go into what we call our non-motor review systems, or our non-motor symptoms. I’ll ask, “Do you feel more anxious? Do you get sweaty? Is there a feeling of just a general unease, or unsettledness in your skin? Do you feel a little bit more confused, a little foggy feeling?” Things like that.

And then sometimes I’ll even ask about pain. “Do you notice if there’s a return of any discomfort that improves after you take your medication?” So when we go through the motor review and then the non-motor review, depending on what they say, I’ll try to focus on the symptoms that they’ve described as an issue or a concern and use that as the barometer to test from visit to visit to see if these symptoms are being managed from dose to dose.

Rajesh Pahwa, MD: Another challenge is quite a few patients have a hard time explaining whether they have, even though they’re having ON and OFF…. You may sit down and talk to them. And tremor, for me, is the most obvious, but it can change with being anxious and have nothing to do with wearing off.

Daniel E. Kremens, MD, JD: And a lot of times it doesn’t even respond to medications.

Rajesh Pahwa, MD: Exactly. So to me, the tremor kind of becomes less of an issue. At times people confuse tremor with dyskinesia. That’s the other thing that can also become a little challenging. And one of the other things we could do is use variables, have patients wear some variable for a few days and then assess how they are, how much OFF they’re having, how much dyskinesia they’re having. I think the future is going to be variables, because either the patients are going to have a hard time understanding OFF, or we’re not going to have enough time to talk about OFF with our patients. So that’s another thing.

Stuart Isaacson, MD: Sometimes when patients can’t identify what OFF is, I try to find out what symptoms improve with levodopa. And then I ask when they come back again, because that really is what OFF is.

Peter LeWitt, MD, M.Med.Sc: Yes. Sometimes something subtle like bradykinesia that can be judged by patients tapping their fingers or feet. Just getting a judge of that. But I would agree with Jill that the psychological impact of wearing off is sometimes the earliest bellwether that medication is dropping off. And of course, the drug is going everywhere in the brain. It isn’t just the motor system.

But I think it’s important for patients to realize that being tired and fatigued is also part of living with Parkinson, and to not overcall the daily cycle, that there are no fluctuations of energy level and so on, which are clearly different in Parkinson than the rest of us. They may be related to how well sleep has occurred, or how well compliance has been with medications. There’s a lot of evidence that patients don’t take medications regularly. And even if you’ve set them up with a 3-hour dosing schedule, which might make a lot of pharmacokinetic sense, that compliance might not be there. There may be no self-awareness of how many times a patient doesn’t get the medication in on a regular basis.

Having on-demand therapies, therefore, makes up for the human condition of nonconsistency. Also, longer-acting therapies or alternative routes of downstream therapies may have a much longer duration of effect. For example, some of the options we have available truly are once-a-day therapies, as opposed to the demands of the immediate release levodopa, and even so-called sustained release products that clearly call for multiple dose compliance during the day.

We can offer these options to patients in the hopes of making up for the nonconsistent use of immediate release levodopa, which is the norm.

Jill M. Giordano Farmer, DO, MPH: Getting back to the idea of sometimes patients not being able to express themselves well, and not getting a good idea as to what their OFF symptoms are versus their ON symptoms, because a lot of our medicines do work quickly and leave the system quickly, sometimes you can actually bring patients into the office OFF and ask them not to take their medications. This is if you have the luxury of time to be able to do it. Give them a dose and then observe them. Typically, we would have done that before…. But you can even do it for the purpose of trying to get a better understanding of what they are experiencing. Then you can show the patient, “Well, this is what ON looks like, and this is what OFF looks like.”

Rajesh Pahwa, MD: But again, that takes time.

Jill M. Giordano Farmer, DO, MPH: It does. And it’s a luxury.

Rajesh Pahwa, MD: And a lot of physicians out there are too busy to have a patient sit through 3, 4 hours in the waiting area. And also, for the patients there’s been an artificial environment, and the same day they may just not have the same experience. The other thing is that a lot of our patients have smartphones now, and having them tape segments during the day and seeing if they are OFF or ON would also be helpful.

Stuart Isaacson, MD: Video is really important, to video the different times a day sometimes. Often, patients will take medications that they’re on during a visit. We speak to a lot of neurologists who say, “My patients don’t have OFF.” But it’s probably because some patients take their medicines that they’re on and can express themselves. They can walk into the office, and get in and out a car, and out of the office. So it’s worth thinking about that.

I think it’s also interesting listening to this discussion, because we talk a lot about the symptoms of OFF—the motor symptoms, the non-motor symptoms. But there are also symptoms that are not OFF. And Raj, you bring up dyskinesia. The patients can get confused.

Rajesh Pahwa, MD: Right.

Stuart Isaacson, MD: Dyskinesia is not OFF. It’s too much ON. And Peter, you bring up the idea of diurnal fatigue and sleepiness from not getting restful sleep. That may just be a sleep problem, not an OFF symptom. Another symptom like that is light-headedness or sleepiness that can occur with postprandial hypotension. Patients may have taken their medicine and then eaten a meal, now their blood pressure is low and they feel sleepy. So it’s worth thinking about how the OFF symptom is really OFF. And then if it is OFF, how can we treat it?