Jim, if you're still reading, I'd like to report my experience with Sinemet, which is unusual but not unknown, as my neurologists and 2 other well-known PD experts have confirmed. I hope you may find some of it relevant.

After I was diagnosed over 6 years ago, I waited 3 years before starting meds because I was doing very well without them, except for a very bad tremor. Also, I noticed that most of the Parkies I met were on various combos of meds, placed great faith in them, couldn't function without them, took their doctors' prescriptions gratefully without question, added on more prescriptions to counter side effects, etc. Although some had a good response to the meds, most were also obviously having much worse symptoms than I, even if time from diagnosis was similar or even less. Of course, that can also be due to different types of PD and different rates of progression. We can never know for sure. But some of the problems seemed to be at least partially caused by some of their many meds, even long before dyskinesia appeared (daytime sleepiness, insomnia, cognitive problems, hallucinations, car accidents from sudden sleep attacks, sedation, compulsive/obsessive issues, dystonia, swollen discolored legs, etc.). So I didn't take meds right away, but I did try to be very objective and very observant, and explored sensible ways to improve my chances & general health (nutrition, exercise, community involvement, fun activities, etc.), and kept up with research in the field.

When I finally did start taking Sinemet at a low dose, after giving in to my MDS's very insistent recommendations, I couldn't even tell whether it was making a difference, but it did not relieve my main symptom, the tremor. After a year, my MDS doubled my dosage (still fairly low) to try to get more of an effect. Very soon my right foot started turning under, my feet dragged badly, my legs cramped & became so weak I could hardly walk or stand, and my right foot jumped so severely I had to stop driving. My fitness and mood took a nosedive.

One day I missed 2 doses (went on a family outing & had none with me), and realized by mid-afternoon that all those symptoms had disappeared. I felt great, normal (except for the usual tremor). MDS told me to go back to my former low dose immediately (she said there was no danger in doing so), and I had none of those problems for more than a year, resumed walking, driving, etc. Unfortunately, in recent months they have returned, perhaps due to the cumulative effect of the Sinemet.

I'm still on the same low dose of Sinemet (plus very low dose of Requip, which seems to help restless legs), and still trying to find the elusive right dose, meds, solution, balance. Tremor persists, but Sinemet seems to help some with a searing mid-back pain (chronic muscle spasm), sleep, slowness, and lack of energy. But if I forget a dose, it's no big deal. I don't have the obvious ON or OFF periods that others report. My current MDS highly recommends DBS for me, but I'm not ready to take that scary step. She says tremor-dominants are often hard to treat effectively with meds (I've tried many), so I'm certainly not alone.

I hope some of this may be helpful or of interest to you. Good luck. Hope to see more of your posts and find out where it leads. PD is unique to each and very unpredictable.