Good day, Brian Collins:
You asked about severe motor fluctuations associated
with long-term use of levodopa therapy.
Patients and researchers have observed for years that
continued medication of levodopa eventually required larger
and larger doses which, in many cases, decreased the
beneficial response to levodopa.
A recent article in the European Journal of Neurology,
37(1):23-7; 1997 dealt with the clinical results of a
comparison between the effect of SInemet and Sinemet CR
on motor response fluctuations and dyskinesias which result
from long-term levodopa therapy.
Dr. Roger Duvoisin, MD in Parkinson's Disease, 2nd ed.,
finds that the most common side effect of levodopa treatment
is the production of involuntary movements, which appear at
higher doses (when brain levels of dopamine are highest) and
usually disappear when the levodopa dosage is reduced.
Dr. Duvoisin believes that the brain has compensated for
a loss of dopamine cells by the receptors becoming more
sensitive to smaller amounts of dopamine. Then when
therapy starts, the levodopa makes the receptors exaggerate
their response. Also, brain cells which do not normally
produce dopamine begin to do so, but are not as selective
and release too much or at wrong times. Levodopa therapy
does not reverse these changes.
Also, check Neurology, 44:1617-22; 1994 for a study
outlining what a patient can do to help optimize the benefits
of levodopa. . . .and lessen motor fluctuations: 1. a.m. dose
of levodopa should be largest. . . try a combination of regular
and CR Sinemet . . . 2. Sinemet CR should be used to
maintain even blood plasma levels, which should be
monitored by patients using a diary to determine optimal
interval between doses . . . 3. Meds should be taken into the
early evening hours (7pm-8pm) based upon individual patient
needs (most PWP can be w/o levodopa for 6 - 8 hrs while
asleep).
I hope this helps.
Stephan 53/7
