Restless Legs Syndrome and Related Disorders - Medications

Dopamine Precursors. The dopamine precursor levodopa (L-dopa) is often used for severe RLS. 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 shown to be well tolerated and safe.)

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Patients typically start with a very low dose taken one hour before bedtime. The dosage is increased until the patient finds relief. Patients sometimes need to take an extended form or to take it again during the night.

Levodopa has a rapid onset of action, and effectiveness is usually achieved within the first few days of therapy. One study reported that a combination therapy of regular-release L-dopa plus sustained release L-dopa was effective in improving sleep.

Serious common side effects of L-dopa treatment are augmentation and rebound. (See side effects section for more information.) Many studies report that augmentation (worsening of symptoms 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). For this reason, experts recommend that L-dopa should only be used intermittently (fewer than three times per week) and that the drug should be immediately discontinued if augmentation does occur. Following withdrawal from L-dopa, patients can switch to a dopamine receptor agonist.

Regimens. L-dopa is fast acting and takes only 15 to 30 minutes before it is effective. The dopamine receptor agonists take at least two hours to become effective. Some experts then recommend regular use of dopamine receptor agonists for patients who experience nightly symptoms and L-dopa for those whose symptoms occur only occasionally.

Side Effects. Common side effects of all these drugs vary but may include feeling faint or dizzy (especially when standing up), headaches, abnormal muscle movements, rapid heartbeat, insomnia, bloating, chest pain, and dry mouth. Nausea may be especially common; adding the drug domperidone may help to relieve this side effect. Because these drugs may also cause daytime drowsiness, special care should be taken when driving.In rare cases, they can cause hallucinations or lung disease.

Dopaminergic agents may also have the following side effects, which can be limiting factors in the value of these medications for RLS. (They tend to be more severe with L-dopa than the newer dopamine receptor agonists.):

Rebound Effect. The rebound effect causes increased leg movements at night or in the morning as the dose wears off.
Augmentation. Long-term use of these agents may eventually intensify (augments) symptoms of restless legs syndrome in the late afternoon or evening. Symptoms of restlessness, in severe cases, extend to the upper part or the whole body and may occur when walking. About 30% of patients who take the dopamine receptor agonists have reported augmentations symptoms compared to 70% who take L-dopa. As the newer agents are taken for longer periods and at higher doses, however, their augmentation rates may become closer to those of L-dopa. In general, however, occasional use of any agent poses a very a low risk for augmentation.
Tolerance (Loss of effectiveness). Long-term use can lead to loss of effectiveness. Adding a drug called entacapone (Comtan) may prolong the duration of action of carbidopa-levodopa therapy (Sinemet), but it can cause nausea.