Katzenschlager_subbed_Layout 1 27/10/2009 17:48 Page 28
Neurodegenerative Diseases Parkinson’s Disease
Apomorphine in the Treatment of Parkinson’s Disease
Consultant Neurologist, Department of Neurology, Danube Hospital, Social Medical Centre East, Vienna
The majority of patients with Parkinson’s disease (PD) develop motor fluctuations and dyskinesias as their condition progresses. In patients
where adjustments of oral (or transdermal) treatment options can no longer adequately control these motor complications, further options
include deep-brain stimulation for a minority of selected patients, intrajejunal levodopa (L-dopa) application via a pump or apomorphine infusion
therapy. The dopamine agonist apomorphine provides relief from off periods when administered as a subcutaneous injection. When applied
continuously via a portable pump system, oral medication can often be reduced considerably and dyskinesias improve in many patients.
Parkinson’s disease, apomorphine, motor complications, dyskinesias, motor fluctuations, continuous dopaminergic stimulation
Disclosure: Regina Katzenschlager has received fees for speaking and consulting from Britannia and Cephalon Germany.
Received: 28 March 2009 Accepted: 29 June 2009
Correspondence: Regina Katzenschlager, Consultant Neurologist, Department of Neurology, Danube Hospital, Social Medical Centre East, Vienna, Austria.
The initiation of antiparkinsonian treatment in early Parkinson’s usually dystonic, often affect the feet and toes and may be painful.
disease (PD) is followed by a phase of good to excellent symptomatic They typically occur in the early morning hours when dopaminergic
response in nearly all patients; this has been referred to as the plasma concentrations are lowest. Incidence figures for motor
‘honeymoon phase’. A stable response may be sustained in some complications vary in the literature. In a meta-analysis of prospective
patients throughout the course of their illness, but the majority will go studies, the risk after five years was found to be around 40%,
on to develop motor complications, which include fluctuations and recent study showed that response fluctuations may be a fairly early
dyskinesias or involuntary movements. phenomenon when subtle signs are considered.
In young-onset PD,
dyskinesias have been reported in up to 94% of patients.
In early PD, the clinical effect following an individual levodopa
(L-dopa) dose wanes slowly and may still be detectable after days to The exact mechanisms underlying motor fluctuations and
weeks. As the disease progresses, the duration of effect gradually dyskinesias are not yet completely understood. While the peripheral
becomes shorter and patients become aware of a missed or delayed pharmacokinetics of L-dopa remain unchanged throughout the
dose as their parkinsonian symptoms and signs re-emerge (‘wearing- course of the illness, pre-synaptic nigrostriatal nerve terminals
off’). Eventually, the clinical response closely reflects peripheral gradually lose their ability to store dopamine. However, evidence
L-dopa pharmacokinetics, characterised by a plasma half-life of 1–1.5 exists for a far more complex basis of the development of motor
hours. More complex forms of on/off fluctuations may emerge, such complications that are likely to be related to long-term
as unpredictable fluctuations, delayed on or dose failures. All of these unphysiological, pulsatile stimulation of the dopamine receptors and
changes in motor functioning may cause considerable distress. involve changes in striatal gene expression and subsequently in
However, off periods may be associated with non-motor symptoms, altered firing patterns of the basal ganglia.
such as acute depression, dysphoria or pain, which may be even
more disabling than the worsening of motor function. The management of motor fluctuations aims to prolong the effect of
individual L-dopa doses by adding catechol-O-methyl transferase
Dyskinesias may be present at peak doses or during the entire course (COMT) and monoamine oxidase (MAO-B) inhibitors, changing the
of the drug. At earlier stages, they may go unnoticed by the patients intervals between intakes and advising patients to avoid taking
while carers are aware of their presence and may be socially L-dopa with meals. Oral or transdermal dopamine agonists are added to
embarrassed. Patients themselves may prefer mild or moderate the drug regime or their dose is increased. While the data for
forms of dyskinesia to the immobility and non-motor symptoms of off amantadine in motor fluctuations are less robust, they may be a useful
periods, but severe chorea and more complicated patterns, such as addition in some patients. All of these measures are limited in patients
ballistic, stereotypic and dystonic dyskinesias, pose a considerable in whom dyskinesias have developed and the increase in the overall
burden on patients. Dyskinesias may be predominant at the onset and dopaminergic load used to counteract fluctuations may induce
end of a dose effect (diphasic dyskinesia). Off-period dyskinesias are dyskinesias. Therefore, an individual dosing and timing regime must be
28 © TOUCH BRIEFINGS 2009