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-----Oorspronkelijk bericht----- Van: Jorge A. Romero, M.D. <[log in to unmask]> Aan: [log in to unmask] <[log in to unmask]> Datum: zaterdag 25 maart 2000 7:02 Onderwerp: Re: Pergolide without Levodopa >> Yes, levodopa causes dyskinesias in advanced PD WHEN YOU INSIST IN USING inappropriately HIGH DOSES OF LEVODOPA despite the dyskinesias. << The alternative is more OFF-periodes when you reduce the doses of levodopa. >> You yourself indicate that "patients with advanced Parkinsonism that reduce the use of levodopa have less dyskinesias." << I mean that if at a certain moment a PWP HAS dyskinesias, AT THAT MOMENT dyskinesias can be reduced by using less levodopa. >> That last statement is NOT the same as what you wish to imply, that patients who delay the use of levodopa have less dyskinesias. << PWP that delay the use of levodopa, do not have LESS dyskinesias, but will experience the dyskinesias a few years LATER. What I mean I perhaps better explain with an example: Theoretical situation 1: - Year 2000: a PWP starts using levodopa. - in the next 10 years his PD progresses and he needs higher and higher doses. - in 2010 the doses of levodopa are at the level of causing dyskinesias. Conclusion: after 10 years of treatment there are dyskinesias Theoretical situation 2: - Year 2000: a PWP starts with mono--therapy using an agonist. - Year 2003: PD progressed and the agonist alone is not enough any more and needs supplementing with levodopa. - in 2013 the doses of levodopa are at the level of causing dyskinesias. Conclusion: after 13 years of treatment there are dyskinesias. Theoretical situation 3: - Year 2000: a PWP starts using levodopa. - in the next 10 years his PD progresses and he needs higher and higher doses. - in 2010 the doses of levodopa are at the level of causing dyskinesias. - levodopa dose is therefor reduced and the remaining dose of levodopa is supplemented with an agonist. - in 2013 the agonist is at maximum dose and increasing levodopa as remaining opportunity will again cause dyskinesias Conclusion: after 13 years of treatment there are dyskinesias. As you wrote in studies only situation #1 and #2 are compared. I think we agree that treatment #2 and #3 are prefered, compared with #1. But you prefer #3 as treatment, while I prefer #2. As you mentioned #3 is not included in studies and I agree with you that it should have. Let us assume for a moment that the theoretical time periods in #2 and #3 are correct. Then IN THEORY in both situations dyskinesias would be unavoidable after the same period (13 yrs). But in PRACTICE the period before dyskinesias in #2 would be LONGER than in #3. Why is that? Kidneys of young people are filtering out medications better/faster than the kidneys of old people. Therefor you need relatively more meds when you are young than at an older age. Therefor in #3 you need relatively higher doses of levodopa (because you start at the relatively "younger" age), resulting in a SHORTER period before the dose of levodopa is reached at which the dyskinesias appear, compared with #2 (where you start with levodopa at a relatively "older"age and need relatively lower doses of levodopa). Therefor IMO #2 is preferable to #3. Hans.