Subcutaneous apomorphine in parkinson's disease: Response to chronic administration for up to five years

Hughes, Andrew; Bishop, Susan; Kleedorfer, B.; Turjanski, N; Fernández, William; Lees, Andrew J.; Stern, Gerald

doi:10.1002/mds.870080208

Cited by 191 publications

(98 citation statements)

References 20 publications

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“…Double-blind clinical trials have shown the effectiveness of subcutaneously injected apomorphine in improving PD motor symptoms (Cotzias et al, 1970;Dewey et al, 2001). Despite these benefits, the longterm use of subcutaneous apomorphine infusions in the United Kingdom has been associated with significant technical difficulties and cutaneous adverse effects (Hughes et al, 1993). Because of these issues, infusions of apomorphine have not been very actively pursued in the United States.…”

Section: Dopamine Replacement Therapymentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

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The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

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Section: Dopamine Replacement Therapymentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

View full text Add to dashboard Cite

show abstract

“…Subcutaneous apomorphine infusions have been used successfully in the United Kingdom for the treatment of motor fluctuations, but there have been significant technical difficulties and associated cutaneous adverse effects. 140 New delivery devices are being developed. Duodenal infusion of LD in a viscous gel (Duodopa) as monotherapy has been demonstrated to be safe, and has provided significant improvement over various oral combinations.…”

Section: Discussionmentioning

confidence: 99%

Current Status of Symptomatic Medical Therapy in Parkinson’s Disease

Factor

2008

Neurotherapeutics

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Summary: Symptomatic medical therapies for Parkinson's disease (PD) have been disease modifying and have led to improvement in daily function, quality of life, and survival. For 40 years, these therapies have been primarily dopaminergic, and currently include the dopamine (DA) precursor levodopa (LD), DA agonists, catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors. The roles of all these classes of agents have evolved, with significant changes occurring since the early 2000s. This article reviews the current literature for each of these classes of drugs, with a focus on efficacy and place in the therapeutic scheme. Levodopa is no longer considered to be toxic and, thus, its early use is not only appropriate but recommended.Ergot agonists are no longer in use, and new agents administered in patch form or subcutaneous injections have been approved. The COMT inhibitor tolcapone, with its significant efficacy, has been reintroduced, and two new MAO inhibitors have been approved. Selected safety issues are discussed, including the incidence of melanoma in relation to LD; pathological gambling and DA agonists; hepatic toxicity of tolcapone; and the tyramine or so-called cheese reaction with MAO B inhibitors. The article closes with a discussion of future directions and new drugs under development.

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“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The general finding is that APO provides more time in motor states near normal performance and less time in 'off' and dyskinetic states as compared to conventional optimised therapy. Improvement in quality of life (QoL) may accompany the increased 'on' time, but so far publications on this aspect of APO infusion are sparse.…”

Section: Long-term Efficacy With Apomorphine Infusionmentioning

confidence: 99%

Long-term Efficacy and Safety with Continuous Dopaminergic Stimulation Pump Treatments in Parkinson’s Disease

Busk¹,

Johansson²,

Nyholm³

2011

European Neurological Review

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Continuous dopaminergic stimulation (CDS) is important for symptom control in advanced stages of Parkinson's disease (PD). The most efficacious approaches are pump treatments with dopaminergic drugs: subcutaneous infusion of the dopamine receptor agonist apomorphine and intestinal infusion of levodopa/carbidopa gel. Both methods decrease motor fluctuations in long-term follow-ups, including parkinsonian and dyskinetic states, when compared to conventional optimised oral therapy. Also non-motor symptoms may be improved. Adverse drug reactions are usually less pronounced although high levodopa doses, which are common with levodopa/carbidopa infusion, may cause hyperhomocysteinaemia and cobalamin deficiency. Technical complications are specific for each infusion strategy. Formation of subcutaneous nodules is the most common problem with apomorphine infusion. Dislocation of the intestinal tube is the most common problem with levodopa/carbidopa infusion. Both pump treatments may be used for 24-hour infusion in selected patients. The long-term experience is reviewed. To conclude, CDS pump treatments may be successfully used for several years in advanced PD. KeywordsApomorphine, continuous dopaminergic stimulation, infusion, levodopa/carbidopa, Parkinson's disease, pump The background is a combination of a number of findings, mainly that:• striatal dopaminergic stimulation is fairly constant in a healthy brain;• striatal dopaminergic stimulation in PD is pulsatile when oral levodopa is used; • pulsatile dopaminergic stimulation causes motor fluctuations and dyskinesias; and • continuous administration of dopaminergic agents may decrease motor fluctuations and reverse dyskinesias.PD is associated with a more widespread pathology than nigro-striatal degeneration and CDS is not the remedy for all problems. But there is firm evidence that continuous dopaminergic drug delivery, probably providing CDS, produces a significant benefit compared to conventional therapy in patients with advanced PD. The evidence mainly stems from studies of levodopa and apomorphine infusions.

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Subcutaneous apomorphine in parkinson's disease: Response to chronic administration for up to five years

Cited by 191 publications

References 20 publications

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Current Status of Symptomatic Medical Therapy in Parkinson’s Disease

Long-term Efficacy and Safety with Continuous Dopaminergic Stimulation Pump Treatments in Parkinson’s Disease

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