Updated: Apr 24, 2019
If you have been close to a Parkinson patient, I know you have heard them mention being 'On' or 'Off'.... and maybe you have wondered exactly what they mean by this... "On? Like a light-bulb? They aren't glowing, that's for sure!"
No, if we were 'glowing' when we were on... yes, that would be strange indeed - either we were abducted by aliens, or we've been too close to a nuclear plant! So in today's blog post I thought I would help clear up what we mean by this - not only for educational purposes but so that you can better understand your Parkie family and friends!
Rather than abducting aliens or radiating nuclear plants, the terms 'on' and 'off' in Parkinson's refers to the state of ones medications and whether they are working or not; 'ON' meaning the meds are working and you are feeling 'normal' (as normal as any Parkie can feel!), and 'OFF' meaning they are not working at the moment. Also, there can be intermediate states - when we are partially on or off. In addition, other things can contribute to these states and how long they last. Well, it looks like it might not be so easy to explain after all, so let's dive into more detail.
First, in order to understand on and off states, we need to take a quick 101 class on Levodopa (or Sinemet as some call it - that is Levodopa's initial brand name). As you know, Parkinson's Disease (PD) is caused mainly by the death of dopamine neurons in the brain. As these neurons die off, less dopamine is produced in our brains. Dopamine is a neurotransmitter that we all use for muscle movement, among other things. As our dopamine levels decrease, we experience the motor symptoms of PD - tremor, stiffness, rigidity, "freezing", and so forth.
Levodopa, discovered in the 1960's, is a drug which gets absorbed into the blood stream and then passes into the brain. The brain then converts Levodopa directly into dopamine. (Automatically, don't ask me how - it's one of those wonders of the human body!) Aha! More dopamine in the brain = better muscle control. In other words, once this happens we Parkies gain back some of those lost motor skills and, well, feel a little bit more 'normal'.
However, because Levodopa is a pill and has to pass through the digestive system, it takes time to get absorbed - and that absorption rate can affect the way the drug works and how effective it is. Did you know that there is only one little section in our entire digestive tract where Levodopa can be absorbed? If it doesn't make it there, or for whatever reason misses that little section - then yep, no Levodopa in the bloodstream, which means the brain has nothing to convert to dopamine in our dopamine starved brain! Not only that, but WHAT we eat can affect Levodopa - for instance, eating a big juicy turkey sandwich (from Thanksgiving) floods your stomach with protein, which competes with the Levodopa, making it harder to be absorbed. This, in turn, can change exactly how much of the drug gets in your bloodstream to make it to the brain.
And if that wasn't enough, for some Parkies like myself, our digestive system slows down due to the disease itself. This means that the pill could remain in the stomach a lot longer than a normal person; in some cases it might be HOURS after you take your med before it finally gets to that spot where it can be absorbed! That's one of my issues with Levodopa - when I take it on an empty stomach (for example, when I get up in the morning) I can usually get it to work (i.e. ON) within 30-40 minutes. Take it after I've eaten a big meal - ex. supper - I can usually expect it to NOT kick on for a mighty long time - hours in some cases. Even worse, sometimes it seems to simply not make it to that 'special' place to be absorbed, which of course means I don't get the ON from the med until I take the next scheduled dose!!
OK, enough on that... Now that we know a bit about Levodopa, what do we mean by being ON? Well, this is the state that we Parkies envy and want the most - to feel 'normal'. ON means that our Levodopa is fully working - it's been absorbed by our brain, and converted into dopamine, which then floods our brain with that neurotransmitter we've lost. For a lot of us, our tremors may go away (or are reduced dramatically); the stiffness melts away, and we begin to feel like we did before we got this crazy disease! For me, I can sometimes actually feel the moment the dopamine hits my brain - it's like this 'wave' goes over my body - a kind of ahhh feeling - my toes un-cramp; my muscles loosen up; the stiffness - especially in my lower limbs - melts away... Suddenly I feel like I could jump up and run a marathon!! (Seriously? Nah, but it does feel that good!)
For a lot of folks, it can also seem like they are coming out of a 'fog' mentally. Now, you may not know this, but dopamine loss can also affect us mentally in that we 'feel' down, slow, confused, tired and the like. That's because dopamine, being a neurotransmitter, not only helps us with movement but also helps us with our feeling and thinking! More dopamine, and our brain can suddenly think and process things better! I know in my case I may feel really tired before taking my dose of Levodopa - so much so that I often go and lay down and rest while waiting for that glorious ON feeling to hit me.
"This is great! It's like it fixes your brain, right?" Well... kinda... Unfortunately there is always a down side to the story (Darn, I don't like that side at all!) If it would just stay that way... well, we wouldn't have Parkinson's would we? But that wonderful extra dopamine gets used up by our brain - sometimes very quickly. And once it gets depleted or goes down below a certain level, the we enter what is known as the 'OFF' state.
Being OFF is exactly the opposite of being ON, and it is the bane of us Parkies. When we are OFF, the extra surge of dopamine that our previous dose of Levodopa provided is gone. And because we have lost a lot of those dopamine producing brain cells, we can't produce enough dopamine to satisfy our brain and body. So in this state, most - if not all - of our symptoms return -- tremor, rigidity, slowness, etc. Also, in a lot of cases, that mental 'fog' returns - we can't think as clearly as we did when ON, our response time is slower - basically our brain slows down along with our body! Ugh, definitely something I do NOT find appealing!!
Sometimes we can go into an off state gradually, or - in my case sometimes - it's like someone actually flipped a switch! One minute I'm feeling good, moving well; and the next - BOOM - I'm off. Other times it is a much more gradual process - I can slowly notice my muscles beginning to stiffen up; my movements slow down; even my thought process can begin to slow down (try writing a blog when you are OFF - you'll know exactly what I mean!) Also things can fluctuate wildly during the day - especially if you've been using Levodopa a long time. Sometimes it seems your ON state lasts right up till your next scheduled dose; other times you may hit your OFF state a lot sooner than expected. And that can make for a LONG day!
So you might think, "Well, just take more Levodopa , right?" Wait, not so fast bub! (Aren't you glad this isn't a test?) Simply increasing Levodopa may not, in most cases, make a huge impact on your ON/OFF times, at least that is my experience - remember, the Levodopa has to go through your digestive tract, get absorbed, and make it up to your brain before it can be used. As I mentioned previously, there are a LOT of things that can interfere with this process - which, in turn, can change exactly how much of the drug stays in your bloodstream to make it to the brain. And when these levels fluctuate in the bloodstream, then more side effects occur. So simply increasing the Levodopa can cause things like Dyskinesias - uncontrollable movements - which in some cases can be just as bad as having your symptoms return! In addition, the longer one has had PD and been taking Levodopa, the less effective it may become. It seems the brain loves having it's dopamine fix every few hours during the day... but give it too little or too much, then it throws a temper tantrum!
This is one of the reasons why we Parkies tend to schedule our physical - and even mental - activities each day to the times when we will be ON - It's no fun being out riding your bike, driving your car, at the gym or even the grocery store and suddenly an OFF time happens... Ugh, talk about inconvenient!! That is why I try to schedule all of my activities (including meals) around my med schedule. I know that can be a pain for those around us.. but hey, that the nature of this disease!
Finally, remember that being OFF may look different for different people. Just as each Parky is different, so their OFF state can be different. Some may experience dystonia (painful muscle cramping); others may find that their tremor starts coming back - mildly at first - as they enter their particular OFF state; or they begin to experience walking/balance issues. Some may have ALL these (and more) symptoms come back!! Unfortunately, these variabilities sometimes make it difficult for those around us to tell if we are in - or starting to go to - an OFF state.
So, now that you know what an ON vs. OFF state is.... how can one try to treat OFF states? Or at the least improve our ON times? Here are a few ideas...
As usual, I have to say here - again - I am not a physician; these are based upon my own personal experiences. ALWAYS seek first the advice of YOUR physician or neurologist!
First and foremost, discuss this with your neurologist. They know your history and can usually provide advice on ways to combat OFF times. For instance, they may be able to suggest a different med schedule, and/or even a change in dose amount (along with a scheduling change) that could mean a big difference!
Always try, if possible, to take your meds at the time they are scheduled - taking them earlier or later can contribute to being OFF. If need be, use your phone to set an alarm for each dose you take during the day.
Modify your schedule - make sure that you plan your day, if possible, around your ON times - especially if it involves movement; things like going to the store, doing your workout, etc.
If meals are a problem, try doing the same with your meal schedule. Plan your meals ahead of time, and try to avoid taking your meds right before or after a meal. In addition, watch for eating too much protein before your med dose - remember protein interferes with Levodopa absorption.
DBS (Deep Brain Stimulation) can help in a lot of instances by simply regulating the time and discomfort of OFF periods. I know that after I had DBS my OFF times were a lot less than before, and definitely not nearly as bad!
Looking forward, there are new therapies being developed and tested right now that may expand your options for treatment of those pesky OFF periods. There is a new under-the-tongue strip that using apomorphine (a dopamine agonist) that can help you get back to an ON state rather quickly. The one I am most excited about is an inhaled form of Levodopa (via an inhaler) that can reach your brain in 10 minutes or less!! Wow!!! Both of these are designed as 'rescue' therapies - to help one get from an unexpected OFF back to ON; and since neither use the digestive system to get into the body, it won't matter what you've eaten or how much protein is in a meal! These will both be a great advancement in the treatment of OFF times - and hopefully, if approved, may even come to market in 2019!
And Now You Know!
So now you know a little bit more about PD and the on/off states of the disease. I hope that by knowing what we Parkies refer to as ON and OFF will help those without PD to better understand us and where we are coming from. When your Parkie friend says they are starting to 'go OFF' you'll know that you may need to slow down a bit for them; and if they tell you they are now 'ON' then it's business as usual - GO MAN GO!
In closing, remember what I said at the beginning about 'abducting aliens'? Well, just a few weeks ago, a UFO was sighted here in West Michigan, near Grand Rapids... So watch out! If you see something glowing in the night, you might want to be careful.. I don't want any of my readers out there being taken by those "abducting aliens"!! How could you read my blog when your out in space? <smile>
Till next time... May the 'ON' be with you!