Identifying OFF Episodes in PD


Laxman Bahroo, DO, and Rajesh Pahwa, MD, comment on the identification and presentation of OFF episodes in patients with Parkinson disease.

Stuart Isaacson, MD: Laxman, this idea of trying to tell our patients about this ON and OFF and even these transition zones, how do you identify to your patients what types of OFF are there? How to look for OFF? What time of the day might OFF occur, and which of your patients do you think about often? All your patients, a few of your patients, how common is this problem?

Laxman Bahroo, DO: This is absolutely something that’s important to discuss. Raj and Bob have both spoken about the variability of OFFs that we have. Of course, I start talking about OFFs when we start levodopa. When we initiate levodopa, I ask them, do you feel that your symptoms are managed? This helps me titrate and adjust levodopa. Maybe not everybody needs a full tablet. Some may do fine with half a tablet, some may need 1, some may need 1 and a half tablets. Typically, what I use is carbidopa/levodopa probably 25 mg/100 mg immediate release as a starting option. Now, with that said, in terms of screening, we start screening every time we see them, asking if they’re lasting from dose to dose. That’s one way to say if the doses are lasting as long, if the doses are providing a robust enough reduction of their symptoms. In many ways it’s challenging if you’ve never experienced an OFF, you don’t know what it is, and as mentioned, people will look at you funny and say, I’m not sure. Then my concern is, are they never experiencing an ON or are they never experiencing an OFF? It’s either extreme, but never something in the middle.

We start asking them if they miss a dose. That’s a great idea, when you take something 3 or 4 times a day, we’re bound to miss a dose. Many times I’ll ask them and say, what happens if you miss a dose? What happens if you took a dose 2 hours late? Did the medication wear off? They may say, no, I’m like this if I miss a dose. Then I say, yes, this is good. You’re on your honeymoon period. Enjoy the honeymoon period, but at some point, when you miss a dose by an hour or two or several hours, you’ll notice the symptoms coming back. Then I try to educate them around different times when sometimes the medications may not kick in as quickly. That’s kind of a front-loaded episode of OFF. Like, I took my medication on time just like I was supposed to, and it just took longer to kick in than the typical time. It’s helpful to define what is a typical time. We talk about typical time being less than 30 minutes. If it’s taking longer than 30 minutes, then you’re getting into a delay. If it’s taking longer than an hour, you’re getting into a potential dose failure. It’s good to talk about that.

In addition to that, we talk about sometimes the most common type, which is the end of dose OFFs, where the medication doesn’t last, an hour before the medication starts to wear off and you gradually ebb away. Then there are the unpredictable ones, which are probably the most scary for patients, that come in without warning. They go into a crash OFF episode. But they’re not as common earlier in the disease, and over the course of time, you may see more progression. Then there’s of course morning akinesia that we’ll see when the morning dose either doesn’t kick in or they wake up in the OFF state, and that first dose just doesn’t kick in. It’s important to tell them, but it’s also important equally to warn them about some of the things that, when OFFs occur, they do to contribute to it. Taking the dose late is an important point. Two, taking the dose close to food, you’re building in a delay. These are what I call self-inflicted OFFs in some ways. Taking a dose with food, taking it late are ways you are actually creating your own OFFs, and these are ways to avoid this. It’s a simple understanding of dose hygiene and how medication works and should be avoided with food. Many times people will say the first time they experienced an OFF was in the middle of the day. They took their food and pill close together, and by 2:30, 3 o’clock, they noticed that their medication wasn’t working as well. There’s a lot of variability to this.

Rajesh Pahwa, MD: I wanted to bring up a couple of other points on here. First of all, the other important thing to ask the patient when you see them in the clinic is, is this the best you are during the day? Because if the patient says, yes, this is my best, they are in the ON state. Or some people may say, well, no, I’m in between my best and my OFF, or my worst so to speak and you get an idea. The other thing that is interesting to find out is, how does the patient do during the day? How are they when they wake up? What happens after they take their first dose of medicine? What happens before the second dose? That also at times would give an idea on how the fluctuations, if they occur, are occurring and when are they having them during the day.

Transcript Edited for Clarity

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