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One of the major decisions that needs to be made by the patient and the doctor is whether using dopamine agonists to delay dyskinesia and possibly delay disease progression is worth the poorer control of motor symptoms which are so effectively reduced by levodopa. In addition, dopamine agonists are associated with more side effects when used as a monotherapy than when combined with levodopa.

An additional issue that doctors should consider before prescribing dopamine agonists is the burden of cost on the patient since dopamine agonists are significantly more expensive than levodopa.

Side-Effects of Dopamine Agonists

Dopamine agonists do have some significant side effects which are mostly cognitive in nature and can significantly interfere with daily living. These include:

• Paranoia
• Hallucinations
• Confusion
• Nightmares
• Nausea
• Vomiting

Some patients develop dyskinesia as well but these are usually not as severe as those seen following levodopa.

Because of the nature of these complications, dopamine agonists are not given to patients who already suffer from any type of cognitive impairment. Recent data has shown a possible link between ergot-based dopamine agonists, such as bromocriptine and pergolide, and dysfunction of cardiac valves. As a result, non-ergot based dopamine agonists such as ropinirole and pramipexole should be tried before the others.

In general, the data so far suggests that dopamine agonists are a significant addition to the arsenal of drugs that are effective in reducing symptoms of Parkinson's disease as well as moderating the side effects associated with levodopa. However, because response to the drugs is so variable, each doctor must evaluate carefully with the patient the choice of drugs as well as the timetable for adding or combining new drugs.

Neupro Transdermal Delivery System

A novel transdermal delivery system (Neupro patch) has recently emerged for the treatment of patients with early Parkinson's disease with a dopamine receptor agonist drug called rotigotine . The patch is applied once a day to the skin and continuously releases the drug through the skin for a period of 24-hours.

In March 2008, the manufacturer of Neupro (Schwarz Pharma) informed healthcare professionals and patients of the recall of Neupro because of the formation of rotigotine crystals in the patches. When the rotigotine crystalizes, less drug is available to be absorbed through the skin and, therefore, the efficacy of the product may vary. Neupro will not be available in the U.S. by the end of April 2008. Healthcare professionals should not initiate any new patients on Neupro and should begin to gradually down-titrate all patients currently using the product per the guidelines in the product labeling. Patients should not abruptly discontinue therapy because abrupt withdrawal of dopamine agonists has been associated with a syndrome resembling neuroleptic malignant syndrome or akinetic crises.

Monoamine Oxidase Type-B (MAO-B) Inhibitors

There are two MAO-B inhibitors that are used in the treatment of Parkinson's disease, selegiline and rasagiline. Dopamine is one of the brain chemicals known as monoamines which are broken down by a protein known as oxidase. MAO-B drugs inhibit or limit the action of oxidase and prevent the breakdown of dopamine in the brain resulting in an enhanced and prolonged effect of levodopa. There has also been considerable debate as to whether the MAO-B drugs used for Parkinson's disease are neuroprotective and possibly delay the progression of Parkinson's disease.