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Dopaminergic drugs include dopamine precursors and dopamine receptor agonists.
Dopamine Precursors. The dopamine precursor levodopa (L-dopa) was once a popular drug for severe RLS. Although it can still be useful, most doctors now prefer the newer dopamine agonists (see below). The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. (Levodopa combinations are well tolerated and safe.)
Patients typically start with a very low dose taken 1 hour before bedtime. The dosage is increased until the patient finds relief. Patients sometimes need to take an extended-release form or to take it again during the night.
Levodopa acts fast, and the treatment is usually effective within the first few days of therapy.
Serious common side effects of L-dopa treatment (and, to lesser extent, of dopamine receptor agonists) are augmentation and rebound. Many studies report that augmentation (worsening of symptoms that occur earlier in the day) occurs in up to 70% of patients who take L-dopa. The risk is highest for patients who take daily doses, especially doses at high levels (greater than 200 mg/day). For this reason, patients should use L-dopa only intermittently (fewer than 3 times per week). The drug should be immediately discontinued if augmentation does occur. Following withdrawal from L-dopa, patients can switch to a dopamine receptor agonist.
The rebound effect causes increased leg movements at night or in the morning as the dose wears off, or as tolerance to the drug builds up.
Dopamine Receptor Agonists. Dopamine receptor agonists (also called dopamine agonists) mimic the effects of dopamine by acting on dopamine receptors in the brain. They are now generally preferred to L-dopa. Because they have fewer side effects than L-dopa, including rebound effect and augmentation, these drugs may be used on a daily basis. About 30% of patients who take dopamine receptor agonists have reported augmentations symptoms. As the newer drugs are taken for longer periods and at higher doses, however, their augmentation rates may become closer to those of L-dopa.
Dopamine agonists have been shown to relieve symptoms in 70 - 90% of patients. Dopamine agonists can be ergot-derived (such as cabergoline) or non-ergot derived (such as pramipexole and ropinirole). The newer non-ergotamine derivatives may induce fewer side effects than ergot-derived drugs:
- Ropinirole (Requip) was the first drug approved specifically for treatment of moderate-to-severe RLS (more than 15 RLS episodes a month). Side effects are generally mild but may include nausea, vomiting, drowsiness, and dizziness.
- Pramipexole (Mirapex) is also approved for RLS. However, patients may fall asleep, without warning, while taking this drug, even while performing activities such as driving.
Rotigotine is a patch preparation. Common side effects include back or joint pain, dizziness, decreased appetite, dry mouth, fatigue, sweating, trouble sleeping or upset stomach.
Other Dopamine Agonists. Other dopamine agonists that have shown some promise in small studies include alpha-dihydroergocryptine, or DHEC (Almirid), and piribedil (Trivastal).
Regimens. The effects of L-dopa are apparent in 15 - 30 minutes. Dopamine receptor agonists, meanwhile, take at least 2 hours to start working. Some doctors recommend regular use of dopamine receptor agonists for patients who experience nightly symptoms, and L-dopa for those whose symptoms occur only occasionally.
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Review Date: 10/15/2010
Reviewed By: Reviewed by: Harvey Simon, MD, Editor-in-Chief, Associate Professor
of Medicine, Harvard Medical School; Physician, Massachusetts
General Hospital. Also reviewed by David Zieve, MD, MHA, Medical
Director, A.D.A.M., Inc.
A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org)
