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Neurodegenerative Diseases Parkinson’s Disease
Moreover, several open-label studies have shown considerable and treatment in collaboration with haematology specialists. As with
sustained antidyskinetic effects in patients on continuous other dopaminergic drugs, a small number of vulnerable patients
subcutaneous apomorphine therapy (44–83% reduction in dyskinesia develop impulse control disorders such as pathological gambling,
severity compared with baseline).
9–12
Dyskinesia reduction is more hypersexuality or other behavioural disturbances on higher doses.
marked in those patients who gradually manage to substantially Confusion or hallucinations may occur. While there is some evidence
reduce their oral dopaminergic therapy, or who achieve ‘apomorphine that neuropsychiatric problems may actually improve compared with
monotherapy’. This is defined as pump treatment only during the baseline, and a positive effect on mood has also been suggested,
13–15
waking day with complete discontinuation of oral drugs, using oral conclusions are limited because none of the available studies of
drugs only early in the morning and at night.
9,11,12
apomorphine pump treatment were randomised.
The observed improvement in dyskinesias is in keeping with Summary
the current concept of dyskinesia formation and is believed to be due Apomorphine induces reliable and quick relief from off periods when
to the replacement of pulsatile with continuous dopamine receptor administered as subcutaneous injections and offers patients with severe
stimulation. Maximum dyskinesia improvement has been observed motor fluctuations better control and more independence. When
several months following the initiation of pump treatment on mean administered via a pump system, excellent improvements in off duration
daily doses of around 100mg. The mean doses tend to remain stable can often be achieved and additionally, in those patients who replace
even when patients use this treatment for years. most or all of their oral drugs with continuous apomorphine, dyskinesias
often improve as well. It is clear that the indications for apomorphine
In practical terms, pump treatment is usually initiated on an inpatient pump treatment are very similar to those for intrajejunal L-dopa
basis. Domperidone is always used as a pre-medication for at least administration (Duodopa
®
) and for subthalamic deep-brain stimulation,
three days and then continued for as long as required. Oral dopamine namely motor complications refractory to oral treatment adaptations.
agonists and subsequently the other oral antiparkinsonian drugs are
gradually withdrawn over weeks to months while apomorphine is While apomorphine has potential adverse effects including skin changes
administered at increasing hourly flow rates. The small and and haemolytic anaemia, it is a less invasive treatment than the other
lightweight pump is usually worn on a belt around the patient’s waist two options and in principle is reversible. Older age, mild to moderate
and the needle is inserted into the abdominal skin into rotating cognitive impairment and many medical co-morbidities do not represent
injection sites (see Figures 2 and 3). The needle must be replaced strict contraindications for a treatment trial with apomorphine. However,
daily. While the usual daily duration of pump treatment is around no randomised controlled studies exist comparing these strategies for
14–16 hours, some patients with severe nocturnal off symptoms late-stage PD and, therefore, the choice of treatment depends on
benefit from 24-hour administration. whether any contraindications for surgery are present, on availability
and local expertise and on the patient’s preference. n
Adverse Effects
Potential side effects of continuous apomorphine treatment include
Regina Katzenschlager is a Consultant Neurologist and
dopaminergic effects including nausea, orthostatic hypotension, leg
runs the movement disorders service at the Danube
oedema or somnolence. Skin-nodule formation is very common but Hospital, Social Medical Centre East in Vienna. She is
usually mild. Rarely, medically relevant skin problems such as
involved in clinical research and teaching with an
emphasis on Parkinson’s disease. Dr Katzenschlager is
abscesses or ulcerations occur, which may require surgical
Chair of the Liaison and Public Relations Committee of
treatment. Occasionally, widespread nodules may impair reliable and the Movement Disorder Society (MDS) and on the
stable absorption of apomorphine. Haemolytic anaemia is rare but
Editorial Board of Movement Disorders as well as
the Executive Boards of the MDS-European Section, the
regular checks for full blood count and Coombs test are
Austrian Parkinson’s Disease Society and the Austrian Neurological Society. Dr
recommended. Coombs test has been described to turn positive in Katzenschlager trained in neurology and psychiatry in Vienna and worked at the National
6–12.5%, although this may be reversible. Development of
Hospital for Neurology and Neurosurgery in London with Professor Andrew Lees.
haemolytic anaemia requires discontinuation of apomorphine and
1. Ahlskog JE, Muenter MD, Frequency of levodopa-related crossover evaluation of a single dose, J Neurol Sci, 12. Manson AJ, Turner K, Lees AJ, Apomorphine Monotherapy
dyskinesias and motor fluctuations as estimated from the 2007;258:137–43. in the treatment of refractory motor complications of
cumulative literature, Mov Disord, 2001;16:448–58. 7. Odin P, Apomorphine Injection Therapy for Parkinson’s Parkinson’s Disease – A long-term follow-up study of 64
2. Stacy M, Bowron A, Guttman M, et al., Identification of Disease, Akt Neurol, 2005;32:50–55. patients, Mov Disord, 2002;17:1235–41.
motor and nonmotor wearing-off in Parkinson´s disease: 8. Deleu D, Hanssens Y, Northway MG, Subcutaneous 13. Alegret M, Valldeoriola F, Marti M, et al., Comparative
comparison of a patient questionnaire versus a clinician apomorphine. An evidence-based review of its use in cognitive effects of bilateral subthalamic stimulation and
assessment, Mov Disord, 2005;20:726–33. Parkinson´s disease, Drugs Aging, 2004;21:687–709. subcutaneous continuous infusion of apomorphine in
3. Schrag A, Ben-Shlomo Y, Brown R, et al., Young-onset 9. Colzi A, Turner K, Lees AJ, Continuous subcutaneous Parkinson’s disease, Mov Disord, 2004;19:1463–9.
Parkinson’s disease revisited: clinical features, natural waking day apomorphine in the long term treatment of 14. De Gaspari D, Siri C, Landi A, et al., Clinical and
history, and mortality, Mov Disord, 1998;13:885–94. levodopa induced interdose dyskinesias in Parkinson’s neuropsychological follow up at 12 months in patients
4. Olanow CW, Obeso JA, Stocchi F, Drug insight: Continuous disease, J Neurol Neurosurg Psychiatry, 1998;64:573–6. with complicated Parkinson’s disease treated with
dopaminergic stimulation in the treatment of Parkinson’s 10. García Ruiz PJ, Sesar Ignacio A, Ares Pensado B, et al., subcutaneous apomorphine infusion or deep brain
disease, Nat Clin Pract Neurol, 2006;2:382–92. Efficacy of long-term continuous subcutaneous stimulation of the subthalamic nucleus, J Neurol Neurosurg
5. Nilsson D, Nyholm D, Aquilonius SM, Duodenal levodopa apomorphine infusion in advanced Parkinson’s disease Psychiatry, 2006;77:450–53.
infusion in Parkinson’s disease – long-term experience, with motor fluctuations: a multicenter study, Mov Disord, 15. Morgante L, Basile G, Epifanio A, et al., Continuous
Acta Neurol Scand, 2001;104:343–8. 2008;23:1130–36. apomorphine infusion (CAI) and neuropsychiatric
6. Pahwa R, Koller WC, Trosch RM, Sherry JH, APO303 Study 11. Katzenschlager R, Hughes A, Evans A, et al., Continuous disorders in patients with advanced Parkinson’s disease: a
Investigators. Subcutaneous apomorphine in patients with subcutaneous apomorphine therapy improves dyskinesias follow-up of two years, Arch Gerontol Geriatr Suppl, 2004;
advanced Parkinson’s disease: a dose-escalation study in Parkinson’s disease: a prospective study using single- (9):291–6.
with randomized, double-blind, placebo-controlled dose challenges, Mov Disord, 2005;20:151 –7.
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