Levodopa is converted to dopamine in the brain. It is effective in managing the initial symptoms of Parkinson disease, however over time the effectiveness is reduced and this results in motor fluctuations. Motor fluctuations are periods of the day with poor or no response to medication (off time). This alternates with periods of improved function (on time).
Over time people on levodopa or dopamine agonist therapy develop involuntary movements. These are called dyskinesia. Dyskinesia in Parkinson disease is caused by medications. This can affect quality of life and may cause disability.
Neurologists from the American Academy of Neurology (AAN) are doctors who treat diseases of the brain and nervous system. They believe people with Parkinson disease should know which drugs and surgical treatments reduce their off time and dyskinesia.
Experts in Parkinson disease reviewed all of the available studies about medical treatments and deep brain stimulation (DBS) for dyskinesia and motor fluctuations. They made suggestions that will help doctors and people with Parkinson disease make choices in their care. In some cases, there were not enough published data for or against specific therapies.
Medical Treatments to Reduce Off Time
Neurologists looked at all of the studies for medications that reduce off time. While there is stronger evidence* for some drugs, there is not enough evidence* to recommend the value of one drug over another. There is strong evidence* that the following two drugs can decrease off time:
Entacapone is in a group of drugs called catechol-Omethyltransferase (COMT) inhibitors. COMT inhibitors increase the length of time that each separate dose of levodopa therapy is effective and reduces per day off time. Entacapone acts in the bowels to increase the amount of levodopa absorbed. Side effects may include dizziness, drowsiness, hallucinations, or change in urine color.
Rasagiline is in a group of drugs called monoamine oxidase (MAO) inhibitors. They slow the breakdown of naturally occurring dopamine and dopamine produced from levodopa. Side effects may include headache, depression, or flu-like symptoms.
There is good evidence* that these medications may reduce off time:
Ropinirole, pramipexole, and pergolide are dopamine agonists. They act directly on dopamine receptors. They act like dopamine; they stimulate the dopamine system. Side effects may include confusion, mild nausea, or decreased appetite. Due to potential side effects such as heart and breathing difficulties, pergolide should be used with caution.
Tolcapone is a COMT inhibitor. In rare cases, tolcapone has caused severe liver damage resulting in death. Notify your doctor immediately if you develop nausea, vomiting, abdominal pain, unusual fatigue, loss of appetite, yellow skin or eyes, itching, dark urine, or clay colored stools. These symptoms may be early signs of liver damage. Liver tests should be done often on people taking tolcapone.
There is weak evidence* that the following drugs may reduce off time:
Apomorphine and cabergoline are dopamine agonists. They act directly on dopamine receptors. Apomorphine is injected like insulin and works rapidly. Apomorphine may cause depression, dizziness, or hallucinations. Cabergoline may cause dizziness, headache, and weakness. As of December 2005, cabergoline was not available in the United States.
Selegiline and orally-disintegrating selegiline are MAO-B inhibitors. Side effects may include dizziness or drowsiness, abdominal pain, and anxiety.
Medical Treatments to Reduce Dyskinesia
The Parkinson disease experts also reviewed all of the available data for drugs that reduce dyskinesia.