ON Time vs OFF Episodes in PD

EP: 1.Role of Levodopa in Managing Parkinson Disease

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EP: 2.ON Time vs OFF Episodes in PD

EP: 3.Identifying OFF Episodes in PD

EP: 4.OFF Episodes During Progression of PD

EP: 5.Impact of OFF Episodes on QOL in PD

EP: 6.Raising Awareness of OFF Episodes in PD

EP: 7.Challenges With OFF Episodes in PD

EP: 8.Initiating Patient Conversations for ON/OFF Episodes in PD

EP: 9.Managing OFF Episodes in PD

EP: 10.Multidisciplinary Management of OFF Episodes in PD

EP: 11.Treatment Selection for Managing OFF Episodes in Parkinson Disease

EP: 12.Initiating Treatment for OFF Episodes in Parkinson Disease

EP: 13.Unmet Needs in Managing OFF Episodes in Parkinson Disease

EP: 14.Using On-demand Therapies for the Management of OFF Episodes in PD

EP: 15.Assessing Effectiveness of OFF Episode Treatment in PD

EP: 16.Novel Therapeutic Administration Routes for Managing PD OFF Episodes

EP: 17.Apomorphine Infusion Devices to Manage OFF Episodes in PD

EP: 18.Emerging Therapies for the Management of PD OFF Episodes

EP: 19.Key Takeaways for Treating OFF Episodes in PD

Stuart Isaacson, MD: That leads us into this idea of motor fluctuations and how this cornerstone therapy of levodopa becomes variable. It gives rise to these OFF episodes. Bob, can you tell us, how do you define OFF, and probably more importantly, how do you identify and define good ON time? That’s the goal I think of treating Parkinson disease.

Robert A. Hauser, MD, MBA: There are a couple of questions layered in there. First of all, how do we define ON? ON refers to when medication is working, and more specifically, when Parkinson disease medication is providing good motor benefit. Usually, we’re talking about levodopa, but it can be other medications as well that have good benefit in Parkinson disease. ON is when patients are experiencing a good motor benefit from the Parkinson medication, and then to make it even more specific than that, I say it’s for mobility, slowness, and stiffness. The reason I define it that way is because as Raj said, tremor is kind of tricky. Tremor may not respond in some patients, and tremor is often quite variable. It often increases with emotional activation. To keep people from getting confused, I like to say it’s when Parkinson medication is providing good motor benefit for mobility, slowness, and stiffness. Then conversely, OFF is when the Parkinson medication through the day is no longer providing good benefit for mobility, slowness, and stiffness. Maybe the medication hasn’t kicked in yet, or it had kicked in, and now it’s not working at a given point through the day. When I think about that, what I do in the clinic is I always ask patients, is your Parkinson medication, particularly levodopa, lasting from dose to dose? If they say yes, or I’m not sure what you’re asking Dr Hauser, that’s a pretty good sign that it is lasting from dose to dose.

A lot of times they’ll say no, it kind of starts to wear off, and something comes back, and that could be tremor, could be slowness, stiffness, mobility. Or they could say, well, in the morning I have slowness, stiffness, or tremor. I also not only ask, is your medication lasting from dose to dose, I also always try to remember what’s happening first thing in the morning. Does it take a while for medication to kick in? I talked about ON and OFF; the other thing you asked me though was what is good ON? This gets tricky because it isn’t just a good ON, it’s not just benefit from medication. It’s a good benefit. It specifically refers to ON without troublesome dyskinesia. You and Raj both mentioned motor fluctuation. ON is when medication is working, OFF is when medication is no longer providing good benefit, has worn OFF. Some people develop a sensitivity to levodopa over time, where they experience hyperkinetic or increased movements. Typically, I call them twist and turning, which is called dyskinesia. If that’s bad enough, it can become troublesome to patients. That’s levodopa-induced dyskinesia, if it’s bad with troublesome dyskinesia that occurs when patients are ON. So, ON with troublesome dyskinesia is too much medication. OFF is too little medication. Both of those things define the bad zone, and in between is the good zone. When patients are ON without troublesome dyskinesia, that’s what we call good ON.

Rajesh Pahwa, MD: One of the challenges that we as clinicians and patients face is ON and OFF is not like a light switch. It is not the patient is ON one minute and goes OFF the other minute. It’s kind of a dimmer switch, so to speak. When they take their medicine, they may gradually come ON, and same thing when their medicine is wearing off, they may gradually get OFF. Often the patients have a good idea, this is my best and I’m ON, and this is my worst, that I’m OFF. The time in between can be challenging for the patients to decide, am I really OFF at this stage, or am I fully ON? That’s where it gets challenging, and the timing on when it is happening does help us that, “OK, I take my pill. I’m not fully ON because my medicine is taking a while to get into my system and for me to be ON.” That’s a very important distinction because a lot of clinician and patients feel that this should be, I’m ON or OFF, but there’s always a zone through which they go.

Robert A. Hauser, MD, MBA: You hit it exactly right because initially patients just get a little wearing OFF, and it’s shallow, so it’s a bit of return of symptoms. As time goes on, that time when they lose their best response becomes greater and they go deeper and get greater return of symptoms. To just say to patients, “Well, are you OFF, or how much OFF,” gets a little tricky, and it’s much more important to ask the patient to describe what’s actually happening over both time and with severity of symptoms. That tells you what you need to do, and also of course ask about impact for them. That’ll help you decide what needs to be done.

Transcript Edited for Clarity