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Yes, Hans, but notice the paradox in your answer to the second question: > 2) Is levodopa causing side-effects (like dyskinesias) in advanced PD? > YES. Patients with advanced PD that reduce the use of levodopa have less > dyskinesias. Yes, levodopa causes dyskinesias in advanced PD WHEN YOU INSIST IN USING inappropriately HIGH DOSES OF LEVODOPA despite the dyskinesias. You yourself indicate that "patients with advanced Parkinsonism that reduce the use of levodopa have less dyskinesias." That last statement is NOT the same as what you wish to imply, that patients who delay the use of levodopa have less dyskinesias. The dyskinesias are dose related - and do occur late in the disease - BUT THERE IS ABSOLUTELY NO PROOF that early use of levodopa speeds the onset of the dyskinesias. Indeed, in the studies involving ropinorole and cabergoline, which have claimed that PWP treated early with the agonist have fewer dyskinesias are seriously flawed and biased. Those studies have only two comparison groups: #1 early treatment with agonist supplemented ad lib with levodopa, or #2 early treatment with levodopa supplemented ad lib with levodopa. Of course, the second group has more dyskinesias - they also have a higher FINAL dose of levodopa. The crucial group necessary for making the study well-rounded was omitted. The third group must be early treatment with levodopa, supplemented later with agonist. Why this third group has been left out of this research is totally incomprehensible since this is the way the drugs are most commonly and effectively used. The only explanation for the omission of this group from the investigations is that the studies were designed by the drug companies with a clear bias and intention to prove that the levodopa group had more dyskinesias. Jorge Romero, MD ----- Original Message ----- From: "Hans van der Genugten" <[log in to unmask]> To: <[log in to unmask]> Sent: Friday, March 24, 2000 9:18 PM Subject: Re: Pergolide without Levodopa > -----Oorspronkelijk bericht----- > Van: Jorge A Romero MD <[log in to unmask]> > Aan: [log in to unmask] <[log in to unmask]> > Datum: zaterdag 25 maart 2000 0:41 > Onderwerp: Re: Pergolide without Levodopa > > > >>>>> > The notion that delaying the use of Sinemet "can delay - or possibly even > prevent" the onset of > certain side effects from Sinemet is speculative at best, and certainly not > universally accepted by > all scientists or Parkinson disease experts. It is well accepted and > promulgated by the drug > companies who sell the dopamine agonists. Indeed, it is a cornerstone of > their propaganda, together > with the notion that levodopa is "toxic." > <<<<< > > The question whether or not to delay the use of levodopa in favour of > agonists, has to be devided into two separate issues: > 1) Is levodopa toxic in the sense that it is speeding up progression of > PD? > 2) Is levodopa causing dyskinesias in advanced PD? > > Historically these TWO questions once were ONE question: is the toxicity of > levodopa causing dyskinesias? > There is NO evidence that the TOXICITY of levodopa is causing the > dyskinesias. > > Having answered that, the two separate questions need to be answered: > > 1) Is levodopa toxic in the sense that it is speeding up progression of > PD? > NO, there is no evidence IN HUMANS that levodopa is toxic, therefor NOT > speeding up progression of PD. > > 2) Is levodopa causing side-effects (like dyskinesias) in advanced PD? > YES. Patients with advanced PD that reduce the use of levodopa have less > dyskinesias. > > Conclusion: > Though levodopa is NOT toxic, there still is another reason for > delaying/reducing the use of levodopa: the dyskinesias in advanced PD. The > delay of the use of levodopa by starting (mono-)therapy with agonists, or > reducing the use of levodopa by a combination of agonist and levodopa, both > result in a longer period without high doses of levodopa, and therefor > result in a longer period before dyskinesias appear. > > Hans. >