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Support for the Long-Term Safety of Levodopa Use

Despite the proven effectiveness and wide use of levodopa, usually prescribed as Sinemet® (carbidopa-levodopa), to manage movement symptoms in Parkinson’s disease (PD), doubts have lingered over the drug’s long-term safety. A new study attempts to put those doubts to rest. In research published October 11 in the journal Neurology, scientists conclude that larger cumulative doses of levodopa, taken for years or decades, do not harm critical brain cells in people with Parkinson’s.

The long-term use of levodopa is associated with dyskinesias (jerky, involuntary movements) and “wearing-off” periods in between doses during which symptoms recur. Scientists debate whether these long term side effects are a result of Parkinson’s progression, or whether they are related to longer use of the medication.

Scientists at the University College of London led by Andrew J. Lees, M.D., reasoned that if levodopa is toxic to dopamine neurons, the more levodopa a person took during the course of Parkinson’s, the fewer dopamine neurons would remain in the brain at death. In new research, they studied brain tissue, retrieved from a brain bank, from 96 people who had died with Parkinson’s. Most of these people had late-stage Parkinson’s at the time of death, and had died, on average, at age 73 after living with Parkinson’s for about 15 years.

The researchers focused on two characteristics of the brain tissue: they counted the dopamine neurons remaining in an area of the brain called the substantia nigra, which is critical in coordinating body movements; and they measured the build-up of the protein alpha-synuclein (in the form of clumps called Lewy bodies) in cells in the cortex and substantia nigra. Lewy bodies are a hallmark of Parkinson’s, thought to contribute to the death of dopamine neurons.

Results:

  • No significant relationship was found between the total amount of levodopa taken and the loss of neurons.  No significant relationship was found between the dose of levodopa and the accumulation of Lewy bodies.
  • A subgroup of study participants, who had early onset Parkinson’s and longer exposure to levodopa, had not lost more dopamine neurons than others in the study.
  • Three of the study participants had very high cumulative doses of levodopa, having taken the drug for up to 31 years. These participants had not lost more dopamine neurons than participants exposed to less levodopa.

What Does it Mean?

The new research supports other evidence that levodopa does not hasten the progression of Parkinson’s. Some physicians have delayed prescribing levodopa, and some people with Parkinson’s have hesitated to take it for fear of its toxicity.

Editorials accompanying the new research affirm that the benefits of levodopa for managing Parkinson’s symptoms far outweigh the risk of harm. There is no doubt that levodopa is the best available medication to provide symptomatic relief of Parkinson’s. Levodopa treatment has shown to substantially prolong the life expectancy of people affected by PD.

The question that this study aimed to address was whether levodopa – in addition to symptomatic relief – has some toxic effects in the region of the brain affected by Parkinson’s. The study did not find substantial supporting evidence that levodopa is toxic, therefore, supporting the practice of treating with levodopa clinically to fight the motor symptoms of PD. While some scientists conclude that levodopa is not toxic, others request additional studies.

In the mean time, it is recommended that people with Parkinson’s see their doctor to develop a medication plan to best alleviate their Parkinson’s symptoms.

Source Date: Nov 18 2011