Global,
Jun 2004: Three to four hours after taking his
drug treatment for Parkinson’s disease
(PD), Tom – who has had PD for the past
nine years – gets a tremor in his right
hand that gradually affects the rest of his
body.
Three to four hours after taking his drug treatment
for Parkinson's disease (PD), Tom - who has
had PD for the past nine years - gets a tremor
in his right hand that gradually affects the
rest of his body.
Doctors call Tom's problem 'wearing-off'. It
happens because the effects of his drugs literally
'wear off' and his symptoms of PD reappear.
What
causes wearing-off?
'Wearing-off' occurs as the duration of effect
of one of the most commonly used drugs to treat
PD - levodopa - diminishes over time as the
disease progresses.
People with
PD have reduced levels of dopamine - a chemical
messenger in the brain that is involved in coordinating
nerve and muscle cells to control movement and
activities such as walking and talking. When
dopamine drops beyond a certain level, symptoms
of PD emerge, including tremor, muscle rigidity
and problems with movement (especially slowness)
known as motor symptoms and also some non-motor
symptoms like anxiety.
The treatment
of PD is based on topping up dopamine levels
with levodopa - which is converted into dopamine
in the brain. Levodopa is a short-acting drug,
which means that each dose only provides additional
dopamine for a few hours. During the first few
years of treatment, because the brain still
provides relatively high levels of dopamine,
little additional dopamine is needed to keep
symptoms at bay and most people have sustained
improvement in symptoms with three doses of
levodopa each day.
Unfortunately,
as PD progresses the number of nerve cells producing
and storing dopamine in the brain falls. With
less brain dopamine available, a dose of levodopa
that initially removed symptoms for four hours
may not provide enough dopamine to maintain
full control of symptoms until the next dose.
The benefit of levodopa literally 'wears off'
before it is time for the next dose. The effect
of each dose of levodopa lasts for progressively
shorter periods of time, and symptoms of PD
reappear. These symptoms then typically improve
15-45 minutes after taking your next dose of
PD medication.
Many people
call the time when their drugs are controlling
their PD symptoms their 'on time' and the time
when they are suffering from wearing-off their
'off time.'
For people
who prefer to think in pictures, here is a diagram
explaining what happens to levodopa levels in
the body over a day:
