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• "Wearing-off" effect - this is the end-of-dose deterioration of symptoms that occurs when levodopa wears off. It may be an indication that the patient must take the drug more frequently. Often, the patient experiences symptoms of dystonia (involuntary muscle spasms which can cause abnormal movements).

• "On-off" effect - also called the "yo-yo" phenomenon, is due to the fluctuation of dopamine levels in the blood. The patient experiences sudden, unpredictable changes in the ability to move. They may go from carrying out a motor activity normally ("on") to suddenly freezing or becoming totally rigid with parkinsonian symptoms ("off"). This can happen several times a day. The "on-off" effect usually indicates either that the patient's response to levodopa is changing or that the disease is progressing.

• Parkinsonian symptoms are more pronounced before the patient takes the first dose of levodopa in the morning.

• Hallucinations

• Restlessness

• Orthostatic hypotension (drop in blood pressure while standing)

When levodopa is introduced to patients with Young Onset Parkinson's Disease, the response to the first dose is dramatic but they are likely to develop associated side effects, primarily dyskinesia, after a few months. Those with adult onset Parkinson's disease usually manifest the same side effects after approximately 3-5 years.

Dopamine Agonists

• Ropinirole (Requip)
• Pramipexole (Mirapex)
• Bromocriptine (Parlodel)
• Pergolide (Permax) - In March 2007, the FDA notified healthcare professionals and patients that pergolide has been withdrawn from the market because it has been linked to serious damage to heart valves.
• Lisuride (Dopergin)
• Cabergoline (Cabaser)

Dopamine agonists mimic the effects of dopamine in the brain and cause neurons to react as if there were enough dopamine present to carry out their function. This class of medications is used either as a monotherapy (single drug) or in combination with levodopa. If used initially as a single therapy, after a certain amount of time, levodopa is added because the relief that the dopamine agonists provide is not sufficient to reduce the symptoms and improve the quality of life as the disease progresses. If levodopa is used as the initial therapy, the dopamine agonists are added in order to prolong the duration that dopamine is active in the brain and thus reduce the "wearing off" effect and dyskinesia.

Dopamine agonists are not as effective as levodopa particularly in alleviating rigidity and bradykinesia. However some doctors feel that since dopamine agonists do have some beneficial effect on parkinsonian symptoms, and the side effects are not as severe as those of levodopa, it is worthwhile to initially prescribe a dopamine agonist and then add levodopa later as needed. Some studies indicate that dopamine agonists as monotherapy can reduce symptoms for up to three years and reduce the risk of developing side effects (dyskinesia and motor fluctuations) for up to 4-5 years. Another advantage of dopamine agonists is that they have a longer half-life than levodopa. Their use does not induce the "wearing off" effect or dyskinesia and may actually moderate these effects when combined with levodopa.

In studies comparing quality of life in Parkinson's disease patients following 4 years of taking either levodopa or dopamine agonists, the resulting quality of life scores were comparable, though there were fewer dyskinesias reported for those patients taking the dopamine agonists (pramipexole or ropinirole). More long-term data is necessary before decisions can be made to reduce reliance on levodopa.