RE: Performance enhancement with selegiline

From: ct (tilley314@attbi.com)
Date: Sat Feb 08 2003 - 01:51:05 MST

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    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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