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Initial treatment of Parkinson's disease. 1997
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The initial treatment of Parkinson's disease should be addressed to improve
symptoms, slow down the progression of the illness and avoid long and short
term complications.

Drugs currently available for symptomatic treatment are levodopa,
dopaminergic agonists, anticholinergics and amantadine.

Levodopa is still the gold standard. Both the standard preparations of
carbidopa/levodopa [Sinemet] or benserazide/levodopa [Madopar] and the slow
release preparations are suitable for initial treatment. However, when to
start levodopa remains controversial.

Dopaminergic agonists are useful symptomatic drugs. They can be used in
monotherapy, but usually require the addition of levodopa to obtain a
satisfactory long term therapeutic response. Used as adjuvant treatment to
levodopa, they help lowering the dosage of levodopa.

Anticholinergic drugs effectively improve symptoms such as tremor and
rigidity but their use is limited by their side effects, particularly in
older people.

Amantadine may be a useful drug for initial treatment of Parkinson's
disease when symptoms are not severe.

Symptomatic treatment should be considered individually in each patient.

If there is only slight disability, treatment may be started with
amantadine alone or with a dopaminergic agonist.

If there is greater disability, levodopa or the simultaneous use of
levodopa and a dopaminergic agonist should be considered.

Anticholinergic drugs should be reserved for young patients with tremor as
the main symptom.

The newer dopamine agonists and inhibitors of catachol-o-methyltransferase
(COMT) are coming therapeutic options.

Selegiline, a MAOB inhibitor with a possible neuroprotective effect, should
also be considered as initial option for Parkinson's disease.

Rev Neurol 1997 Aug;25 Suppl 2:S163-S169
Kulisevsky J, Lopez-Villegas D
Hospital de La Santa Creu i Sant Pau, Barcelona, Espana.
PMID: 9280684, MUID: 97383890

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Selegiline in de novo parkinsonian patients: the Finnish study. 1995
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In an earlier report of our placebo-controlled selegiline trial on de novo
parkinsonian patients, we have shown that the need to start additional
levodopa therapy is significantly postponed by using selegiline monotherapy.

Now we report the two-year interim results of the double-blind continuation
of the trial in 44 patients after the introduction of levodopa to the
earlier therapy with placebo or selegiline (21 and 23 patients,=
 respectively).

The clinical disability was assessed by three rating scales.

The daily dose of levodopa needed to maintain an optimal condition had to
be increased progressively up to a 52% higher level in the placebo group
than in the selegiline group (543 +/- 150 and 358 +/- 117 mg, respectively,
p < 0.001).

The number of daily doses of levodopa was also statistically significantly
higher in the placebo group during the 24 months' observation period (p <
0.01).

The ratio of levodopa doses that was expected to stay the same contrarily
significantly increased suggesting that selegiline would, besides having
the levodopa potentiating effect, also have a beneficial influence on the
progression of the basic cerebral dopamine deficiency.

The combination of selegiline and levodopa was well tolerated, and the
adverse event profiles did not differ from each other.

In conclusion, early selegiline therapy allows a significant saving in the
subsequent levodopa dosage.

This saving seems to become even stronger along with the treatment time.

Acta Neurol Scand 1995 Mar;91(3):177-182
Myllyla VV, Heinonen EH, Vuorinen JA, Kilkku OI, Sotaniemi KA
Department of Neurology, Oulu University Hospital, Finland.=7F
PMID: 7793231, MUID: 95313520

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Selegiline in de novo parkinsonian patients: the Finnish study. 1993
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Selegiline (L-deprenyl) has been recommended as an antiparkinsonian drug to
be used as an adjunct to therapy with L-dopa, if and when L-dopa starts to
lose its effect.

However, initial selegiline monotherapy followed by L-dopa may be both
effective and safe.

A double-blind, placebo-controlled trial was carried out in previously
untreated patients with Parkinson's disease randomized to receive
selegiline (10 mg/day; 27 patients) or placebo (25 patients) until L-dopa
treatment became imperative.

Three rating scales were used for assessment.

The study design continues to be double-blind even after L-dopa is=
 introduced.

L-Dopa was needed after 545 +/- 90 days in the selegiline group.

This was significantly later (p =3D 0.03) than after placebo (372 +/- 28=
 days).

Disability was less severe in the selegiline group, and there were no
serious adverse effects.

A nearly twofold dose of L-dopa was needed in the placebo group to achieve
a sufficient therapeutic effect during long-term treatment.

These results show that selegiline is safe and effective as monotherapy in
early parkinsonism.

It delays the need for L-dopa treatment and reduces the amount of daily
L-dopa required.

This could be explained by either a symptomatic effect or neuroprotective
efficacy or, more likely, a combination of both.

Mov Disord 1993;8 Suppl 1:S41-S44
Myllyla VV, Sotaniemi KA, Vuorinen JA, Heinonen EH
Department of Neurology, Oulu University Hospital, Finland.
PMID: 8302307, MUID: 94134091

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Selegiline in de novo parkinsonian patients: the Finnish study. 1991
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In order to investigate the efficacy of selegiline as a primary treatment
in Parkinson's disease (PD), we carried out a placebo controlled,
double-blind prospective trial.

Fifty-four de novo patients with PD were randomized to receive either
selegiline (10 mg/day) or matching placebo.

We continued the monotherapy until the initiation of levodopa therapy
became necessary.

The disability of the patients was evaluated with three different rating
scales at baseline, after 3 weeks, 2, 4, 8, and 12 months, and every 4
months thereafter.

Fifty-two patients were eligible for the final analysis: 27 in the
selegiline group and 25 in the placebo group.

The median duration of time without levodopa was 545 +/- 90 days in the
selegiline treated patients and 372 +/- 28 days in the placebo treated ones
(p =3D 0.03).

The disability of the patients was significantly milder in the selegiline
than in the placebo group up to 12 months.

More patients showed symptomatic improvement in the selegiline than in the
placebo group.

However, the symptomatic effect alone did not explain the prolongation of
the time without levodopa in the selegiline treated patients.

Selegiline was well tolerated and no severe side effects were encountered.

Acta Neurol Scand Suppl 1991;136:70-72
Myllyla VV, Sotaniemi KA, Vuorinen JA, Heinonen EH
Department of Neurology, University of Oulu, Finland.
PMID: 1801540, MUID: 92197291

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Symptomatic effect of selegiline in de novo Parkinsonian patients. 1993
The French Selegiline Multicenter Trial.
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The French Selegiline Multicenter Trial was carried out in 1990 to
investigate whether the disability of de novo patients with parkinsonism
could be improved during the first 3 months by monotherapy with selegiline
(10 mg/day).

A double-blind, randomized, placebo-controlled clinical trial was conducted
over 3 months with 93 patients from 13 centers.

Symptomatology was assessed on various disease rating scales, including
Hoehn and Yahr, Hamilton Depression Rating Scale, Unified Parkinson's
Disease rating scale, and Schwab and England scores, as well as
self-assessment.

Biological and clinical parameters were measured for tolerability, and
efficacy was investigated with special reference to the point at which
therapy with L- dopa had to be started.

Selegiline was significantly superior to placebo on the various motor
rating scores, and depressive scores were significantly improved at the end
of 3 months.

Adverse effects were rare and minor.

Therefore, selegiline could be the therapy of choice for the treatment of
de novo parkinsonian patients.

Mov Disord 1993;8 Suppl 1:S36-S40
Allain H, Pollak P, Neukirch HC
Centre Hospitalier Regional et Universitaire de Grenoble, France.
PMID: 8302306, MUID: 94134090

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"Widening horizons" in the clinical application of selegiline. 1992
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The first paper on the beneficial effect of selegiline in the treatment of
Parkinson's disease was published in 1975.

In the first ten years several clinical studies were conducted world-wide
to prove its efficacy as an adjuvant to the basic 1-dopa therapy.

Although the design, duration and number of treated patients were
different, the overall results were mainly uniform.

The patients treated with 1-dopa / selegiline combination showed marked
improvement in disability, increasing duration of 1-dopa effect and marked
lessening of dose-related fluctuations were seen, compared to those treated
with 1-dopa alone.

It became also generally evident that selegiline allows a 10-30% decrease
in 1- dopa dose.

The investigations in which selegiline has been used as monotherapy have
been triggered by some purely clinical experience and by the discovery of
pathobiochemical mechanisms of MPTP toxicity which causes fairly similar
clinical picture to Parkinson's disease and can be successfully prevented
by selegiline.

The newly diagnosed parkinsonian patients treated with selegiline alone
showed marked improvement in their clinical state.

Beside the actual clinical effect on disability, selegiline slowed down the
progression of Parkinson's disease.

The latter fact has been proven in the largest clinical trial ever done
with selegiline (DATATOP).

Selegiline monotherapy can delay the need for 1-dopa substitution by around
one year or longer.

Based on the continuously growing clinical experiences it became widely
accepted that selegiline is the drug of choice as initial treatment for
newly diagnosed parkinsonian patients.

Acta Pharm Hung 1992 Sep;62(5):259-264
Kovacs A
Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Rt., Budapest.
PMID: 1488911, MUID: 93142571

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