Challenges With Morning OFF Episodes in Parkinson Disease


Expert neurologist Peter A. LeWitt, MD, reflects on the challenges inherent in treating morning OFF episodes in patients with Parkinson disease.


Peter A. LeWitt, MD: Motor fluctuations are a common problem in Parkinson disease after patients have been treated with levodopa for a few years, sometimes as little as 1 or 2 years but generally 3 or more years. Motor fluctuations can be categorized in various ways, including delays in onset of medication benefit, a short duration of each dose of levodopa, perhaps only 2 or 3 hours. Sometimes the unpredictability of absorption or whether a particular dose will go to work for that patient is what characterizes motor fluctuations, and there are other phenomena as well. The freezing of gait that some patients experience after several years may not actually be related to levodopa. Likewise, the early morning OFF time refers to the lack of medication dosing for many hours from the day before. There are a number of different motor fluctuations. Any one patient can be experiencing a combination of 2 or more. Then on top of that, involuntary movements or dyskinesias can also be experienced by that same patient.

The reason that morning OFF episodes can be problematic is that upon arising is a very demanding time in our lives. We want to get going, we want to have breakfast, we want to wash and dress, we want this all to be rather safe. And the medication regimen that people are generally taking with oral levodopa has a minimum time of absorption of 15 or 20 minutes with the immediate-release forms. And other factors can slow the absorption of medication as well. At the critical time of waking up and wanting to get going, it can be delayed. Some patients have 30 or more minutes of delay, and it’s unpredictable. A patient who must get out the door within a certain time frame may be finding this very frustrating.

A patient who is experiencing morning OFF episodes is living with a burden of unpredictability in their life. The medication taken the day before has no effect the next day because levodopa has a relatively short clearance half-life. A patient is waiting for that medication to kick in. It may require holding off on breakfast because that meal can slow the absorption of oral medicines. And then altogether, Parkinson disease is an unpredictable disorder. Some days there isn’t as good a response to a particular dose of levodopa for factors that we don’t quite understand for everybody.

For a patient who responds to levodopa, there can be a significant impact on quality of life if there isn’t the regularity and the reliability of medication going to work. Levodopa is a drug that’s been quite miraculous in its effectiveness for treating Parkinson disease in general, but it becomes increasingly capricious in its onset of effect, its duration of effect, and whether a patient will achieve the full action that they desire. And sometimes a particular dose is absorbed too rapidly for good control, and patients might experience involuntary movements or dyskinesias. Altogether, levodopa is a drug with its imperfection of irregularity in its absorption process, and that’s especially evident in the morning hours upon arising.

Transcript edited for clarity.

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