From: ct (tilley314@attbi.com)
Date: Sat Feb 08 2003 - 01:51:05 MST
At 12:56 PM 2/7/2003 -0500, you wrote:
>gts wrote:
> > If you were really on top of this subject, Rafal, then I believe you
> > and I would not be arguing whether selegiline is neuroprotective.
>
>### OK, I am just too incompetent to discuss PD with you.
I think it is just a temporary side-effect of off label camaro use!
====================================================
PD ~560,000 patients in US
~$11billion per annum for PD medication alone
====================================================
Research has shown that levodopa can increase the risk of heart disease in
Parkinson's patients.
January 30, 2003 3:58 PM GMT (Datamonitor) - A study published in the Archives
of Neurology suggests a link between levodopa and increased homocysteine
levels. This new evidence of adverse side effects will increase the demand for
treatments that can delay the need for levodopa.
===========================================================
http://archneur.ama-assn.org/issues/current/abs/noc20099.html
...patients with Parkinson disease (PD) may have elevated homocysteine
levels resulting from methylation of levodopa and dopamine by catechol
O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl
donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is
rapidly converted to homocysteine, levodopa therapy may put patients at
increased risk for vascular disease by raising homocysteine levels...
Patients whose homocysteine levels were in the higher quartile had
increased prevalence of CAD (relative risk, 1.75...
===========================================================
http://www.aan.com/professionals/practice/pdfs/int_par.pdf
... Specific questions include:
1) does selegiline offer neuroprotection;
2) what is the best agent with which to initiate symptomatic treatment in
de novo PD...
Using evidence-based principles, a literature review using MEDLINE, EMBASE,
and the Cochrane Library was performed to identify all human trials in de
novo PD between 1966and 1999. Only articles that fulfilled class I or class
II evidence were included.
Based on this review, the authors conclude:
1) Selegiline has very mild symptomatic benefit (level A, class II
evidence) with no evidence for neuroprotective benefit(level U, class II
evidence).
2) For PD patients requiring initiation of symptomatic therapy, either
levodopa or a DA can be used (level A, class I and class II evidence).
Levodopa provides superior motor benefit but is associated with a higher
risk of dyskinesia.
Ideally, if a drug were available, initial treatment of PD should slow
disease progression. Once symptomatic benefit is required, treatment should
reduce disability without inducing complications over the long term.
4. Dopamine agonists are effective for all features of the disease, but are
not generally as effective as levodopa and are more expensive than
levodopa(class I, II).
5. Selegiline. Class I evidence suggests a mild therapeutic and partial
protective effect from selegiline,but confirmation of the neuroprotective
effect is needed. Selegiline also has antidepressant activity that offers
modest direct symptomatic benefit for PD
The goal of treatment should be to obtain an optimal reduction of
parkinsonism with a minimal risk of long-term side effects.
Given the controversy generated by the report of Lees et al. that mortality
was increased in patients with PD taking selegiline, studies utilizing
selegiline in patients already receiving symptomatic therapy were included
to address the safety of selegiline in this patient population.
Selegiline.What is the role of selegiline in the treatment of early PD?A
neuroprotective benefit of selegiline through decreased free radical
production was proposed and resulted in the DATATOP (Deprenyl and
Tocopherol Antioxidative Therapy of Parkinsonism) clinical trial.
There is no convincing evidence for increased mortality with selegiline
whether it is given in combination with levodopa or as monotherapy (class II).
Recommendations for patients with PD who require symptomatic treatment
* Initial symptomatic treatment of patients with PD with selegiline in
order to confer mild,symptomatic benefit prior to the institution of
dopaminergic therapy may be considered (level A, class II evidence).
* There is insufficient evidence to recommend the use of selegiline to
confer neuroprotection in patients with PD (level U).
Conclusions. Cabergoline, ropinirole, and pramipexole treatment of PD
patients requiring dopaminergic therapy results in fewer motor
complications(wearing off, dyskinesias, on-off motor fluctuations)than
levodopa treatment after 2.5 years of follow-up.Cabergoline, ropinirole,
and pramipexole treatment of PD patients requiring dopaminergic therapy is
associated with more frequent adverse events including hallucinations,
somnolence, and edema than levodopa therapy.
Recommendations. In patients with PD who require the initiation of
dopaminergic treatment, either levodopa or a dopamine agonist may be used.
The choice depends on the relative impact of improving motor disability
(better with levodopa) compared with the lessening of motor complications
(better with dopamine agonists) for each individual patient with PD (level
A,class I and class II evidence).
=============================================================
Time for one of those Bayesian network thingees.
[The Maxwell and Dirac equations, for example, govern most of physics and
all of chemistry and biology. So, in principle we should be able to predict
human behavior, though I can't say I've had much success myself] --Hawking
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