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The Use of STALEVO to Improve Motor Fluctuations in Parkinson’s Disease
Adding a dopamine agonist or increasing the dosage of a dopamine
Table 1: Levodopa–DDCI plus Entacapone Is Well Tolerated
agonist, if the patient is already being prescribed this option, is a
without Marked and Frequent Side Effects Compared with
possibility that has been shown to be effective in reducing motor
Treatment with Conventional Levodopa–DDCI Alone
fluctuations;
20–24
however, this strategy increases the risk of dopamine-
Patients (%)
agonist-related side effects. Such antiparkinsonian drugs could induce Adverse Events* Levodopa–DDCI plus Levodopa–DDCI plus
hallucination/delusion, especially in aged patients or in patients with
Entacapone (n=806) Placebo (n=497)
cognitive decline.
25
This renders such an option difficult to consider in
Dyskinesia/hyperkinesia 30.4 17.5
these patients. Dopamine agonists can also be responsible for increased
Nausea 13.6 7.4
Parkinsonism aggravated 13.5 15.3
daytime somnolence, accompanied in certain cases by narcolepsy.
26
Urine discolouration 10.8 0.0
Recently, dopamine agonists have been recognised as being associated
Diarrhoea 10.3 3.8
with rare cases of complex behaviour disorders, such as the impulse
Dizziness 7.9 5.6
control behaviour syndrome, with gambling, compulsive shopping and Abdominal pain 7.3 4.2
hypersexuality.
27
Such side effects, which can lead to major social Constipation 7.2 4.2
repercussions, may affect up to 14% of patients treated by dopamine
Hypokinesia 6.9 6.2
agonists. With the ergot-derived dopamine agonists, an increased risk
Fatigue 6.1 3.6
of cardiac valvular fibrosis has also been reported.
28
Adapted from Parkinson Study Group, 1997;
7
Rinne et al., 1998;
8
Poewe et al., 2002;
9
Brooks, 2003;
10
Haapaniemi et al., 2001;
12
Myllyla et al., 2001.
13
*Occurring in >6% of patients in the levodopa–DDCI plus entacapone arm.
The use of a monoamine oxidase-B (MAO-B) inhibitor is another
Table 2: Different Therapeutic Options for a Parkinsonian Patient
option that has been investigated as a treatment option for reducing
Suffering from Motor Fluctuations
motor fluctuations associated with conventional levodopa therapy.
MAO-B is an enzyme that catabolises brain dopamine, consequently
Option Advantages Disadvantages
increasing and prolonging its action. Several controlled studies have Increase levodopa No risk of introducing a Daily treatment
confirmed the efficacy of MAO-B inhibitors to decrease the severity of
dose frequency new drug; treatment with more constrained
motor fluctuations.
29–31
MAO-B inhibitors are usually well tolerated,
the natural agonist
Sustained-release Treatment with the Limited impact for
but the amphetamine metabolite of the MAO-B inhibitor selegiline can
form of levodopa natural agonist reducing motor fluctuations
lead to hallucination or delirium, especially in aged patients.
32
Potential for late-evening
administration
The demonstrated efficacy in correcting motor fluctuations and the
Dopamine agonists Effective for decreasing Introduction of a
good tolerability of levodopa–carbidopa–entacapone makes its choice motor fluctuations non-natural agonist
pertinent in the management of such complications. Levodopa–
Good efficacy to decrease Risk of side effects
carbidopa–entacapone provides an option that does not require the
the severity of dyskinesia
addition of a drug with neurological effects, since the action of
Monoamine Effective for decreasing Risk of side effects linked
oxidase-B inhibitors motor fluctuations to the amphetamine
entacapone is exclusively at a peripheral level. Levodopa–carbidopa–
(especially catabolite
entacapone optimises levodopa, the natural agonist, and reduces the
of selegiline)
number of drug administrations required (see Table 2).
Levodopa–carbidopa– Optimisation of the Caution needed when used in
entacapone combined natural agonist patients with dyskinesia
Practical Management of STALEVO to
form Effective for decreasing
Decrease Motor Fluctuations
motor fluctuations
Detecting Motor Fluctuations psychiatric, vegetative and sensory. Depressive mood or anxiety,
Motor fluctuations reduce quality of life and may also be responsible for palpitation, dyspnoea, sweating, numbness or miscellaneous pain can
a harmful plasticity within the basal ganglia; thus, early detection of be reported in the hypodopaminergic state. All of these symptoms
levodopa-related complications for early treatment is mandatory. The have the specificity of being non-permanent during the day, and when
detection of motor fluctuations is usually achieved by interviewing the carefully analysed appear to fluctuate in relation to the level of efficacy
patient and/or the patient’s care-giver. Specific questions may help of the antiparkinsonian treatment.
enhance early detection of motor fluctuations; these include enquiries on
changes in motor state (i.e. impairment of gait or of hand movement, Analysing Motor Fluctuations
occurrence of tremor) during the day; the patient’s condition in the early Once motor fluctuations have been detected in a patient, these
morning before the first antiparkinsonian drug intake and one hour after complications require careful analysis before initiating treatment. Again,
drug intake; whether the motor state worsens before drug intake; and the main analytical tool is to interview the patient or care-giver. The goal
what happens when there is a delay in the drug intake. for the practitioner is to attempt to establish the patient’s ‘typical day’. The
analysis needs to focus particularly on the patient’s condition the morning
Non-motor fluctuations can also occur in PD, and these complications before the first dose of the antiparkinsonian drug, the time taken for the
may be more difficult to demonstrate;
33
however, non-motor first dose to act and the duration of its effects, the time of the ‘bad periods’
fluctuations also lead to disability and reflect non-optimal functioning (i.e. tremor, movement disability, gait impairment) and the quality of sleep.
of the basal ganglia. Accordingly, the detection and correction of non- Furthermore, the analysis needs to take into consideration any co-existing
motor fluctuations is also an important clinical consideration. Three dyskinesia. The use of a home diary offers an interesting tool for analysing
main categories of non-motor fluctuation can be differentiated: motor fluctuations.
34
Patients are asked to indicate their condition hourly,
EUROPEAN NEUROLOGICAL REVIEW 39
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