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Dr. Fernandez

Post of the Week: Levodopa/Sinemet

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What about levodopa? Is it really the best thing that ever happened to Parkinson’s patients or should we avoid it like the plaque?


It is with no exaggeration when we say that levodopa revolutionized the treatment of Parkinson’s disease and remains the most efficacious symptomatic treatment for the motor features. It effectively alleviates bradykinesia, rigidity, and, in some patients, tremor. Its benefits lead to prolonged functional independence and reduced functional impairments and disability for most patients in the moderate to advanced stages of the disease, and it definitely increases longevity!


However, the downside of early initiation of levodopa therapy is that in approximately 40-50% of patients whose disease is progressing and who were initially treated with levodopa, motor complications such as dyskinesia, wearing off, and on-off fluctuations begin to emerge after about 4-6 years. The complications of prolonged use and other side effects of levodopa, including nausea, vomiting, and orthostatic hypotension, limit the use of levodopa in early Parkinson’s disease and have contributed to the traditional clinical practice, for younger patients (younger than 65-70 years), of delaying the initiation of levodopa therapy (Schapira and Olanow 2003). Results of a recent study known as ELLDOPA (Earlier vs Later L-DOPA), however, challenge this traditional approach (Parkinson Study Group 2004)


The ELLDOPA study was a double-blind, placebo-controlled trial designed to assess the effect of levodopa on disease progression in 361 patients with early Parkinson’s disease (Parkinson Study Group 2004). Patients were randomized to receive low dose, or high dose levodopa, or placebo for 9 months followed by a 2-week “washout” period (where all patients were taken off their medications). The results showed a greater increase in the severity of parkinsonism in the placebo group compared to the low-dose and high-dose levodopa. However, as high as 25% of the high-dose levodopa group developed fluctuations and/or dyskinesias after only 9 months. These clinical results indicated that treatment of patients with levodopa early in the course of disease showed a dose-dependent relief of their symptoms, and suggested that delaying initiation of treatment deserved reappraisal. Owing to the short duration (2 weeks) of the levodopa washout, it remained unclear whether the early use of levodopa slowed disease progression.

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