When should levodopa therapy started in Parkinsons Disease

When should levodopa therapy started in Parkinsons Disease

When should levodopa therapy be started in the treatment of Parkinsons Disease? 

The mainstay in the treatment of Parkinsons Disease is the replacement of dopamine.

This therapy was introduced in the 1960s. Instead of using dopamine, which does not cross the blood–brain barrier, the current approach consists of combining levodopa and carbidopa.

Levodopa is transformed into dopamine, and carbidopa is a peripheral inhibitor of the enzyme dopa-decarboxylase.

The inhibition of this enzyme in the periphery, but not in the brain, decreases substantially the required levodopa dosage and the occurrence of gastrointestinal side effects (nausea and vomiting).

In Europe and other countries, benserazide is available as an inhibitor of dopa-decarboxylase. 

The effectiveness of levodopa may be limited by early motor fluctuations and dyskinesia attributed to nonphysiological stimulation of dopamine receptors by multiple and higher cumulative levodopa doses.

This effect is believed to occur more in younger Parkinsons Disease patients. A rational strategy is to start levodopa when the parkinsonian symptoms begin to impair activities of daily living or to interfere with social and occupational functioning.

A typical starting dose for carbidopa/levodopa is 25/100 mg tab, 1-2 tabs or 3 times/day.

Maintenance doses of 200 to 600 mg/day of levodopa may be needed in patients with moderately advanced PD.

Although some Parkinsons Disease experts believe that delaying levodopa therapy is a prudent approach, longitudinal studies show no difference between patients who started on levodopa versus those who started on a dopamine agonist.

Several recent studies have suggested that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy but rather with longer disease duration and higher levodopa daily dose.

These studies show that patients who were started on levodopa relatively early in the course of the disease have very similar long-term outcomes as those with levodopa-sparing therapies.

The approach to early therapy must be individualized, and generally those patients who require symptomatic therapy in order to maintain a satisfactory level of functioning at home and at work are started on levodopa early, whereas those whose symptoms are not troublesome may be started on dopamine agonists.

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