Educating Patients on Signs of Parkinson Disease OFF Episodes

Peter A. LeWitt, MD: With a spectrum of problems that can lead to OFF episodes, how do you use that in the clinical setting? How do you get patients and their caregivers, families, or those who are interested in this disorder to use this information to make decisions on their own and to give you good feedback so that you can efficiently try out the various remedies we have to maintain more consistent ON time? The challenge is to listen very carefully to their complaints and focus in on timing, dosing, and what’s happened in the past. What’s happened with the addition of a dopaminergic agonist versus a levodopa extender, such as a COMT [catechol-O-methyltransferase] inhibitor or an MAO-B [monoamine oxidase-B] inhibitor? How much improvement has there been? It’s also important to provide a little bit of a primer on levodopa. Therapeutics 101 is that the immediate-release form of this drug is somewhat irregularly absorbed, and the fastest that it can absorb is in about 15 minutes.

In addition, its clearance from the bloodstream is at 2½ to 3 hours and food will only delay its uptake. These basic facts should be put in the mind of the patient. Some doctors have used home diaries as a tool to try and figure out the pattern of ON and OFF episodes and used these in clinical trials to great advantage. But I think the easier method is just to ask a patient to try and jot down how long a typical dose, especially that first dose of the day, takes to work. How long does it last? Is there a meal effect?

With these 3 basic facts in mind, you have a chance to adjust their medication regimen. You can take away unnecessary doses at bedtime because that bedtime dose is not going to last until morning. The patients may need medication during the nighttime to deal with OFF episodes that are making it difficult to sleep. But 1 of the challenges in getting the patient educated is to realize that they have control over adjusting medication. They can take extra. They can take less. If somebody is having dyskinesia in the afternoon but the morning dose is just right, perhaps they can adjust the levodopa dose in the afternoon or evening because the accumulation of levodopa effect may address dyskinesias there. But not every dose has to be changed. Caregivers and patients have a great role in observing and making decisions. I think it’s very important to have a good discussion in the office, perhaps with some diagrams drawn out because this will save you the phone calls, the frustrations, and the need for a sooner visit with someone who can go off in the world and realize what’s going on.

The other point I emphasize is allowing for a large enough period of time for observation. Everybody with Parkinson disease is a little bit different on each day. It’s very easy to focus on the medications or what you’ve eaten for breakfast or how well you slept the night before. But in reality, it’s an extremely variable condition with good days and bad days, despite the same medication being used. The best thing to do is to look for the bigger patterns to get an idea of what’s changing with respect to the stability of their typical medication regimen.

This is the best we can do for improving the quality of life of patients. Unfortunately, we don’t have the cure at hand. We know Parkinson disease is often not progressive, but the motor fluctuation, dyskinesia, delay in onset of effects, and all of these things crop up as years go by. At least we have different therapeutic approaches to deal with these, as well as the possibility of experimenting in any 1 patient to see what might be better. We have some new options that have come along in therapeutics for Parkinson disease beyond the medications. This patient was taking apomorphine, ropinirole, and levodopa with entacapone. There are other options to experiment with as well as new therapies that are currently in clinical trials.

One of the challenges in communicating with patients and their caregivers is getting a good sense of what OFF episodes really mean. “Off” implies that someone is completely immobile and the worst Parkinson disease symptoms have emerged. In reality, the severity of symptoms varies very much throughout the course of the day. OFF should be construed as not being optimally controlled. In talking to patients, you can use a 0 to 5 scale where 5 is the best level of control. “Do you feel normal at 5?,” you might ask them. The emergence of a minor symptom like tremor could be called an OFF episode, even though it isn’t a problem of mobility. Regarding the most severe OFF episode, you might ask a patient, “What are you like in the morning?” or “What’s it like if you’ve forgotten to take 2 or 3 doses?” But it’s nice to get a scale established in their mind of the spectrum of symptomatology they experience.

It might be the tremor, for example, if it’s never well controlled. Another problem in terms of trying to differentiate OFF from ON is dyskinesia. Unfortunately, some patients—unless they’re carefully guided to understand the concept—think that the twisting, turning, fidgety movements of dyskinesia represent an undermedicated state. Perhaps a diagram that you’ve drawn out in front of them might be the best learning aid to indicate that there is an optimal range of medication effect and that there is a threshold for effect.

You might even put arrows with typical timing, such as 15 minutes to get to that point at the fastest. You might indicate if dyskinesia is peak-effect dyskinesia or possibly the rarer form called “diphasic dyskinesia,” where dyskinesia began in the first 10 or 15 minutes and also occurs at the end of the dose cycle at 3 or 4 hours.

Communicating what OFF episodes are and that they have a potential therapy option—such as changing the timing of medication, changing the amount taken, or having the option of an on-demand or rescue therapy—are all parts of the effective communication that you can have, usually in 5 minutes or less if you’re good at it. Work at trying to make sure the patient understands the concepts so that as they communicate to you what a medication has done for them or what medication has changed, you don’t experience the problem of having to reinvent the wheel on the phone with them or having your staff receiving ambiguity in terms of the feedback.