OFF Episodes in Parkinson's Disease: Terminology and Patient Experience


Stuart Isaacson, MD, FAAN, defines the terminology of OFF episodes in Parkinson’s disease and what “OFF” means from a clinical perspective.

Stuart Isaacson, MD, FAAN: One of the big challenges we face in treating our patients with Parkinson disease is OFF episodes. The word OFF doesn’t have a great deal of meaning. When a dose of levodopa is no longer providing symptom benefit, it’s that void, that black hole. We try to describe this in different ways at the end of a dose when symptoms reemerge and get better with the next dose. When there are symptoms and you take a dose of medication, and you have benefits but the symptoms come back, that’s an OFF episode.

But it’s an important problem because initially when we treat our patients with oral levodopa, it works robustly and consistently for hours upon hours. But after a few years, patients begin to recognize that each dose of levodopa lasts 4 or 5 hours, and then 3 or 4 hours, a shorter and shorter duration of benefit. When levodopa is not providing symptom benefit, that’s what we refer to as an OFF episode.

When we talk to our patients, we often use the word OFF. It’s a word that doesn’t have a great deal of meaning. It came about in the mid-1970s at meetings where individuals were getting an early experience from treating their patients with levodopa. I’ve read the transcripts of these meetings where they described how their patients had improved and benefited from a dose of levodopa. Then the benefit wasn’t there after a few hours, and the symptoms came back. Individuals described this as like shutting a light off, flipping a light switch. The patient looked great when they had levodopa benefit, but a few hours later, they no longer looked good and had their symptoms back. With this [reference to] shutting the lights off, the word OFF became the terminology to refer to those times when there was no longer benefit from a dose of levodopa.

We’ve used this word to mean a number of things over the years. OFF is when you’re not having benefit. OFF is when the medication benefit is wearing off. OFF is when you don’t take medication. OFF can be all the hours of the day. If you add up all those minutes and hours between doses and during doses when you don’t have full benefit from a dose of levodopa, that could be what we call OFF time. We’ve defined OFF for purposes of clinical trials, using the Hauser diary, as a time when you don’t have a benefit from a dose of medication. We’ve defined OFF in other ways in the literature as well.

But what we haven’t done is capture the patient experience. What does a patient experience when a dose of their cornerstone levodopa therapy isn’t providing benefit after a few hours? What do they feel like? How anxious do they get? What do they think is going to happen? How do they know when to take the next dose? How long is it going to take until they have benefit again? There’s a period of time when a patient isn’t having full benefit and has to wait for that next dose to be taken and to work so they begin to have benefit again. We may call that OFF, but patients have a different way of characterizing that. I don’t think the word OFF captures the entire physical, mental, emotional, and psychological constellation of their own motor and nonmotor symptoms. We need to come up with better words and a better lexicon to help our patients describe what they’re experiencing, and how what they’re experiencing impacts what they’re doing—how it prevents them from fully doing their work, exercise, teaching, or family activities and impacts their quality of life. We’re going to emerge from this era with a better word than OFF that helps our patients describe their plight.

Transcript edited for clarity

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