Background
My mom started on madopar about 3 years ago, didn't work well, so started sinemet about 2 years ago, which stopped the bradykinesia and generally helped. She also takes a small dose of lexapro (SSRI) for depression and a generic multivitamin.

Sinemet dosage
The neuro started her on 2 x 25/100 sinemet three times a day. She developed tardive dyskinesia (pursed lips and movement in mouth area) some time after this, so neuro told her to only take 2 x sinemet (25/100) once in the morning and again once in the afternoon. My mom did that for a while, but then decided on her own to cut back to taking just 2 sinemet 25/100 in the morning, which is what she has been doing for the last year.

Typical Day
Her day goes like this (I'm going to use my own relative scale from 1-10 for PD symptoms, with 10 being the best she feels when she's "on"):

9:00am - [7.5 out of 10] - Wakes up, feels relatively OK and takes her 2 x sinemet (25/100); typically makes her feel sightly nauseated.

9:30 - 10:00am [10 out of 10] - Sinemet kicks in; eats breakfast. Good energy level, can go for a brisk 45 minute walk without problems.

2:00pm [4 out of 10] - Seems like this is when she starts going "off", left hand clenches up, muscle rigidity in her neck, feeling generally tight.

3:00pm+ [7.5 out of 10] - After resting in a chair or bed for about an hour, she feels better again, more or less like she does when she wakes up. She has not taken any more sinemet or other supplements. She gets through the rest of the day feeling generally well, but at a lower energy level than when she is "on" with her Sinemet.

New information after skipping 2 days of Sinemet dosages:

Day 1 without any Sinemet ... she felt about a 7.5 out of 10
Day 2 without any Sinemet ... bradykinesia kicked in, very low energy, obviously missing the Sinemet ... 4 out of 10

If she wasn't taking sinemet at all, I'm fairly sure her bradykinesia would re-emerge along with her blank stare and the other PD symptoms she originally showed a few years ago.

Questions/personal thoughts related to these observations (please keep in mind that I have no real experience with PD, just what I've read):

1. What hypothesis can you draw based on the fact that she can function fairly well (7.5 out of 10) in the afternoons with only a single dose of sinemet in the morning, and that she feels her worse (4 out of 10) when that dose is wearing off at around 2pm every day ... and also on the 2nd day after not taking any sinemet?

Here are some of my thoughts, which of course are just wild guesses based on the little I know:

a. there is still enough residual l-dopa from the morning sinemet or cumulatively in her system to allow her to function at a 7.5 until the next day or even 2 days (since Day 1 of not taking sinemet, she still felt about at 7.5 out of 10). The half-life of sinemet is about 2 hours, but don't know about the cumulative, long-term effect?

b. her brain is able to and expects to produce some l-dopa in the afternoons ... enough to feel about a 7.5, but has learned to expect an external source of l-dopa in the morning ... the combination of the 2 get her by?

2. The fact that she doesn't take any sinemet in the afternoon and is able to function at a slightly lower level of energy (7.5), but doesn't "need" the Sinemet, makes me want to talk to her neuro (or not?) about looking into an alternative, more natural, and complementary therapy for the afternoon. The idea being, that if it works, maybe it can become her primary treatment and reduce/eliminate the Sinemet over time. It seems like it's a good "test bed" (a.m. vs. p.m treatment) since in both cases she feels around a 7.5 before taking anything.

I am especially thinking about some combination or subset of the precursors to l-dopa ... l-tyrosine, folic acid (precursor to Tetrahydrofolic acid), Nicotinamide (precursor to NADH) or NADH, and iron [I haven't checked drug/supplement contraindications yet]. Theoretically, I think it would make sense to try boosting her internal l-dopa biosynthesis from l-tyrosine by supplementing with l-dopa precursors that may be lacking ... instead of only focusing on external delivery of l-dopa. I've read a number of studies where some people have had success with l-tyrosine and even iron to reduce PD symptoms or at least reduce the level of external l-dopa that they needed to take. Worth a try? Thoughts?

Any insight, thoughts, ideas would be greatly appreciated.

Hi Nick,
I recall you mentioning she has a recent history of falls which makes me think she may be a bit underdosed with levodopa at different times.

She takes 200mg at the same time right? Perhaps spread it out more.

You also mentioned she previously took Madopar, same thing as Sinemet only different brand and (I thought) not marketed in U.S. If she has any Madopar tabs (pink ones) left maybe try that as it has the advantage over Sinemet tabs in that it's easily quartered for smaller more frequent dosing which may reduce her PD symptoms and smooth out her on times.

Dyskinesia I think would be more likely to occur in someone still on a relatively low dose of levodopa with a larger amt taken in the one dose.
Although I think eventually she'll end up a bit more prone to dyskinesia with levodopa it sure beats the the rigidity and akinesia associated with no or too lower doses of it.

My advice is to get a neuro or MDS she likes and respects and listen to them.
PD is a bugger of a thing to have but more so if you stuff around listening to the wrong advice.

These Drs don't always get it right but I think they're more likely to be on the right path than the alternatives out there.

In a nutshell try less levodopa but more frequently.

i have the same pattern, morning dose works ok, noon less well. i think its a food problem. amino acids are actively absorbed in the small intestine and thru the BBB.
similar AA's will compete with l-dopa for active transport sites and slow down or even reduce absorption of l-dopa. remember, i think only 1% gets to the brain, the rest is broken down in the tissues.
stomach emptying may be a factor, i try to take my meds with 6oz of warm liquid and at least an hr after eating..
i take 100mg sin at 5:30am, 200mg cr at 7-8am, 100mg sin at noon, 200mg cr at 2.
your mother is older, you might want to take 1/2 cr at 2. i find i get best relief from a combination of regular and controlled release but cr is tricky for me, sometimes takes too long to kick in, sometimes i feel like i've taken too much. but i appreciate it's longer affect.

getting adequate carbidopa is important.
Studies show that the peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 to 100 mg a day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.
http://www.medsafe.govt.nz/profs/Dat...Sinemettab.pdf

an egg has over 1 gram of tyrosine, you think you need supplements or we have a tyrosine deficiency?what is the limiting factor in dopamine production?

http://www.lucilleleader.com/l/congress.html

You need to think about this as a wider picture and be aware of other things happening, especially in the dawn period. Cortisol is rising as is insulin. Half a dozen more may play a roll. Your afternoons, by contrast, may be "sedate" as the "tides" pause at the moment of reversal. The day as a whole will affect the response, especially the stress levels. Any infection flareups ditto.

It gets very complicated, but you can gather comparative data from those first hours. What has a better effect as the irst dose? How long does it take to come on and how long does it last? At what point will a second dose of something be needed to sustain a desirable state? It is still messy, but it is as close to a baseline as you're going to get.

I also think that spreading the dose is better, seems to me that she needs a big boost in the morning once any residual dopamine production of her own has declined, but perhaps its better spread out, the thing to do is avoid peaks and troughs, then the lip pursing etc is less likely to happen. The slight nausea she gets could be avoided by spreading the dose. Ginger is good for this and for lots of other problems in older people. A ginger tea, or small piece of ginger preserve may help. But agree that a good MDS/neuro/pd nurse will help sort this out. In treatments like duodopa which drips feeds l-dopa very slowly into the system dyskinesias disappear, it is fluctuations that give the nasties.

I have heard that the Leader book on nutrition is wonderful, am hoping to look at it myself, that would be a good place to start......

Best wishes with sorting it out
Lindy