Impact of OFF Episodes in Parkinson’s Disease


Daniel E. Kremens, MD, JD, discusses the standard of care for patients with Parkinson disease and when patients start to experience OFF episodes.

Daniel E. Kremens, MD, JD: For over 50 years, carbidopa-levodopa has been the foundation, the gold standard, for the treatment of the motor symptoms of Parkinson disease. But with time, the efficacy of levodopa wanes, and we describe these episodes as OFF time. OFF time is when the medication fails to give the expected benefit, or that benefit wanes before the next dose of medication. When the medication is delivering that expected benefit, we describe that as ON time. Physicians will often ask the patient: are you OFF or ON? That’s what we’re looking for. Are you getting that expected benefit? Are you ON? Or is the medication failing to give you that expected benefit or wearing off before your next dose, so you’re OFF?

When do patients begin to experience OFF episodes? OFF episodes are very common in Parkinson disease, and some patients begin to experience OFF episodes as early as 1 to 2 years into therapy. In fact, in one study, patients were developing OFF episodes within 42 weeks at higher doses of levodopa, but most patients begin to experience OFF episodes within 5 years of starting levodopa therapy. Roughly 50% of patients will have OFF episodes by 5 years. By 9 years, the vast majority of patients, over 90%, are experiencing OFF episodes.

OFF episodes are very different for every patient, and sometimes patients can have a difficult time recognizing their OFF episodes. OFF episodes can be motoric in nature, meaning the reemergence of their tremor, their slowness or bradykinesia, or rigidity. They may have difficulty getting in and out of a chair, their voice may get soft, or they may have nonmotor return of symptoms. This is very common. Patients will sometimes describe a sense of dread or anxiety as their medicines wear off. They might feel foggy, confused, and anxious. There can be lots of manifestations of OFF, motoric and nonmotoric.

Is there any way to predict when patients are going to develop OFF? There are some risk factors, but we can’t make a clear prediction. Most patients by 5 years are going to be experiencing OFF, so it’s important that, as caregivers, we ask patients about them. Some risk factors for developing OFF include things such as length of time with Parkinson disease, length of time on medication, and the amount of medication. Most patients who are taking levodopa at doses higher than 400 mg are at a higher risk of developing OFF episodes. The longer you’ve had Parkinson, the higher your risk is of developing OFF episodes. Younger-onset patients tend to develop OFF episodes a little more quickly. These things are all potential risk factors, but it’s almost impossible to predict when each patient is going to develop OFF episodes. For patients, OFF can be very variable. They may be fine some days but other days have marked difficulty with OFF. There are a number of reasons why this may be the case for patients.

OFF episodes and OFF time have tremendous impact on patients. It limits patients’ activities and their days, and it impacts not only the patient but also caregivers, who become more fearful about going out, particularly without a caregiver. If they get out and get stuck in an OFF episode, how are they going to get back home? They start to limit their activities and engage less in things such as physical therapy or socialization because they’re afraid. What happens if I go out to my class and now I can’t move? What if I go out to dinner and get stuck? I’m going to feel embarrassed. I’m going to feel shame. These things have tremendous impact on patients and are very limiting to the patient and the caregiver.

Transcript edited for clarity.

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