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Movement Disorders, Parkinson's Disease
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Subcutaneous Apomorphine Infusion – An Update

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Published Online: Jul 15th 2012 European Neurological Review, 2012;7(Suppl. 1):8–12 DOI: http://doi.org/10.17925/ENR.2012.07.S1.8
Authors: Regina Katzenschlager
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Abstract
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Article Information
Abstract:
Overview

Continuous delivery of dopaminergic drugs is an important treatment strategy to delay or reverse motor complications in Parkinson’s disease (PD). Subcutaneous apomorphine (APO) infusion has been shown (in uncontrolled studies) to significantly reduce ‘off’ time and dyskinesia duration and severity, and long-term data show the beneficial effects persist for several years. There is some evidence that the maximum antidyskinetic effect of APO infusion may be attained when oral medications are reduced or discontinued, making monotherapy an important clinical goal. Recent studies demonstrate possible positive effects of APO infusion on the non-motor symptoms of PD. However, more trials are needed to assess the neuropsychiatric effects of this treatment. Moreover, randomised controlled trials are needed to compare APO infusion with best medical treatment and with other invasive treatments such as levodopa/carbidopa intestinal gel infusion and deep brain stimulation.

Keywords

Parkinson’s disease, levodopa, continuous dopaminergic stimulation, subcutaneous apomorphine, non-motor symptoms

Article:

The management of the later stages of Parkinson’s disease (PD) is greatly impacted by non-dopaminergic problems, such as dementia, depression and falls, and by the emergence of motor complications including motor fluctuations and dyskinesias. Motor fluctuations, such as ‘wearing off’ and unpredictable ‘off’, affect 30–100 % of patients.1–4 Dyskinesias can be ‘on’ (mostly choreatic), biphasic (often dystonic) or ‘off’ (dystonic). In the later stages of the disease, there is a loss of nigrostriatal neurons and a concomitant loss of storage capacity. Positron emission tomography imaging of dyskinetic and non-dyskinetic patients showed no difference in dopamine receptor binding, which suggests that dyskinesias are unlikely to be the effect of alterations in striatal dopamine receptor binding.5 On the other hand, levodopa-induced changes in synaptic dopamine levels increase with the progression of PD.6 These changes in synaptic dopamine concentration may be a factor in the emergence of peak-dose dyskinesias.

The pharmacokinetics of levodopa in the periphery, such as plasma half-life clearance, volume of distribution and maximum plasma concentrations, remain unchanged.7 However, the absorption f oral levodopa, which takes place primarily in the duodenum, is affected as gastric emptying becomes more erratic.8,9 Pharmacodynamic postsynaptic striatal changes in gene expression,10 neuropeptide formation11 and discharge patterns of the basal ganglia12 result in complex feedback loops.13 Furthermore, non-dopaminergic factors such as glutamate, opioids and serotoninmay be involved in the development of dyskinesia.14 Sprouting of extrasynaptic dopaminergic terminals may also lead to dysregulateddopamine release.15

One of the most important factors associated with the risk of motor complications is the degree of neuronal loss. In rats whose nigrostriatal system had been lesioned unilaterally by 6-hydroxydopamine, the level of levodopa-induced motor complications was related to lesion size.16 In humans, if the first dose of levodopa is given at an advanced stage of the disease, motor complications may develop within a matter of weeks.17 Furthermore, patients with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced chronic and severe parkinsonism developed dyskinesias or ‘on-off’ fluctuations within months of starting levodopa treatment.14 Additional factors that contribute to a greater risk of motor complications include younger age at disease onset,3,18 lower bodyweight19,20 and genetic factors.21

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Disclosure

Regina Katzenschlager has received consulting and lecturing fees from Abbott, Cephalon, Lundbeck, Teva, Boehringer, GlaxoSmithKline, Novartis and Genus.

Correspondence

Regina Katzenschlager, Department of Neurology, Danube Hospital, Langobardenstr. 122, 1220 Vienna, Austria. E: regina.katzenschlager@chello.at

Support

The V International Forum on Parkinson’s Disease (Helsinki, Finland, 6–7 May 2011) was funded by an unrestricted educational grant from Abbott. Abbott funded the development of this supplement by ESP Bioscience (Crowthorne, UK). Emily Chu and Nicole Meinel of ESP Bioscience provided medical writing and editorial support to the author in the development of this publication. Abbott had the opportunity to review and comment on the publication’s content; however, all decisions regarding content were made by the author.

Received

2013-06-22T00:00:00

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