Once you commit to carbidopa/levodopa therapy, what is the typical starting dose, how long does it take for symptoms to ameliorate, and what should you expect in terms of long-term stability and/or deterioration (adverse fluctuations of “on-off” time) of motor symptoms over time?
you come to the point that the patient requires symptomatic treatment and you've agreed that the best treatment for this patient and frankly for probably most other patients you will see diagnosed with Parkinson's disease is to start with Carby dopa. Levodopa. It's a compound name carby dopa levodopa. But Leva dopa is the active ingredient because that is transformed into dopamine when it gets to when it crosses the blood brain barrier. Carby dopa really just stays in the periphery and it is there as an anti nausea medication. And so that is to make carbon Dopa or levodopa more tolerable. So you decide the usual, the smallest dose is 25 over 100 mg. That means it's 25 mg of carbon dopa and 100 of levodopa. Normally I start with one tablet three times a day. And now in super sensitive individuals may be in more frail patients. You might want to start with a half a tablet three times a day In a rather strong patient in his or her 50's or early 60s with no other comorbidities. A strong G. I system, you may want to start with one tablet three times a day. Now the pharmacist will always say don't take it with food because of the protein interaction but in the beginning that's not really a concern. My bigger concern is whether they will tolerate the drug or not. So I actually tell them to take it with breakfast, lunch and dinner one so that they don't forget it because no one forgets to eat and to so that they can tolerate the medication over time If they develop motor fluctuations or some sensitivity, we could I take it or give them instruction to take it without food. But for now I take it with food one tablet three times a day. Now, Parkinson's disease is a progressive illness. It is not a static disorder like stroke or some other illnesses and therefore you do have to follow them over time because that can change as their disease progresses. Their requirement for levodopa dosage will change. In fact, almost universally, the time will occur where they will need more levodopa doses. And so usually we would increase to four times a day, I think more than four times a day becomes A compliance issue. But if they're disabled enough, maybe you can push to five times a day. Now I have exceptional patients who are on it six times or seven times a day or around the clock, but usually 3-4 times a day would be convenient five times a day, a little bit of an exception. Um And then if as the disease progresses, they might be starting to experience motor fluctuation. The most common motor fluctuation type is that of wearing off when the symptoms recur when the medication effect do not last or no longer last until the next dose and it falls short. So that's what we call wearing off. And in that case you have the option of either um uh shortening the duration between doses to a certain extent or maybe increasing the dose of levodopa so that it lasts a little bit longer or adding what we call levodopa extender. So things that prolong the duration of effect or the half life of levodopa, such as inhibitors like mine, Ceo empty inhibitors, like an to Capone and other FDA approved products. So in the beginning though we start with levodopa, you start low and you go slow. That's always our general rule. Watch for the most common and warn your patients of the most common side effects, which would be nausea and vomiting a little bit of sleepiness in the beginning, some lightheadedness, those are the most common ones. And um, we warned them that these are transient of course, if it's too much they should call you and maybe you need to decrease the dose a little bit if it's just not that significant. If they can weather the storm, it'll usually go away on their own. It's nice to have a check on them in two months or three months at the very latest so that you can go to the next step higher if they need it or you can stay there if they're quite happy with where things are going. Um, I also tell my patients that not all symptoms of Parkinson's disease will respond to levodopa, the two biggest symptoms that will respond to levodopa would be the rigidity and the brady keynesian. Now its response to tremor is a little bit less consistent. Sometimes it works like magic and sometimes it could be medication resistant or sometimes it's somewhere in the middle. The unfortunate motor symptom that do not respond well does not respond well to levodopa would be gait instability. Unfortunately, so of the four motor symptoms of Parkinson's disease, two of them rigidity and brady keynesian respond very well. One tremor may or may not respond as well and one which is gate instability. Traditionally do not respond or does not respond very well and physical therapy would be your best treatment to address that problem.