-----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.