Hello, I am posting this question for a friend, but I have a similar interest (I'm currently taking 2 or 3 25/100 sinemet a day and not always at the same time each day):

I am concerned, like everyone else prescribed medication for Parkinson's, to minimise my risk of developing levodopa-induced dyskinesia. There seems to be a fairly established position that the risk is a function of how old you were when you first developed symptoms, how long you've had the disease, and how much levodopa you're taking. No-one can do anything about the first two, so we focus on the third.

There seems to be a newer view emerging, that perhaps the key mechanism causing dyskinesia is not so much the total consumption of levodopa as such, but rather the process of "spiking" between "on" and "off" periods, when the level of dopamine in the brain rises and falls in between levodopa doses. I have seen some academic papers discussing the biological mechanisms (that I am definitely not qualified to understand!), but my consultant has mentioned this theory as well, and has prescribed a 24 hour agonist patch partly to smooth out the spiking.

It does raise a practical question that I'm struggling with. Most days I can get by with his recommended regimen of one Sinemet tablet three times a day (12/50) plus a Neupro patch once a day (4mg), and deal with the slowness of movement as the effects wear off until the next dose of levodopa. However, some days a fourth dose of levodopa would enable me to do so much more – go out in the evenings, day trips out by public transport or extended driving without problem. Should I stick to 3 and adapt my lifestyle accordingly, or can I tweak it to 4 some days to keep my life as active as I want … in which case is it safer just to change my regimen to 4 a day all the time?

I am really interested in whether other people have heard about this idea that spiking is a major factor in the development of dyskinesia, and what the practical implications might be for levodopa treatment.