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Medication is initiated at low doses which are then increased gradually to the minimum level of effectiveness. The timing of medication administration is very important in order to ensure relief at the time of greatest need when the symptoms are strongest, such as the early evening hours. Medications may be given only on an as needed basis or on a more regular schedule. If one drug is not sufficiently effective in reducing symptoms, the dose may be adjusted or another medication may be initiated as treatment either from the same or from a different class of drugs. A drug may also be suspended temporarily if the patient develops a tolerance for it and needs to keep increasing the dose in order to get relief. Some patients experience remission and then medications may be withdrawn or their dose may be reduced.

The response to dopaminergic agents in patients with restless legs syndrome is almost universal. Two types of drugs included in this class of medications:

• Dopamine precursors
• Dopamine agonists

Dopamine Precursors

Levodopa has been used for over 20 years and its effectiveness has been confirmed in many studies. It is usually given in combination with carbidopa (a dopa-decarboxylase inhibitor) in a formulation called Sinemet. While levodopa increases the level of dopamine in the brain, carbidopa prevents other enzymes from breaking down the available dopamine, thus increasing the amount of time that dopamine can remain active in the central nervous system. As a result, the dose of levodopa can be reduced and as well as the subsequent side effects. Sinemet is formulated with varying ratios of the two medications and a controlled-release formulation (Sinemet CR) is also available.

Sinemet is taken orally either on an as-needed basis or on a regular schedule. It is usually taken on an empty stomach in order to increase absorption and it is recommended that Sinemet not be taken with a high protein meal since protein interferes with the absorption into the blood. Restless leg syndrome is typically so responsive to levodopa that when the patient improves after commencing this drug, that is a confirmation that the diagnosis of restless legs syndrome is correct. The medication is typically taken shortly before going to sleep (about one hour) and results in:

• Reduction of periodic limb movements
• Reduction of severity of restless legs syndrome symptoms
• Improved sleep quality
• Reduced daytime sleepiness

When taken on an empty stomach, levodopa is fast acting, usually within 15-20 minutes. Because of its short half-life (amount of time it takes for the body to eliminate half of the medication), levodopa is effective in preventing symptoms from developing when taken shortly before an event in which the patient wants to be symptoms free, such as a movie or a meeting. When taken shortly before bedtime, its effect may wear off quickly and patients may wake up during the night with symptoms of paresthesia and the need to move their legs. In order to combat this problem, an additional dose of levodopa may be prescribed before bedtime. Alternatively, a controlled release form of levodopa/carbidopa (Sinemet CR) has been developed in order to extend the effectiveness of the medication since it delivers a steady supply of levodopa over an extended period of time and this also prevents the levels from falling too low in the blood which would bring on additional symptoms. However, the duration between taking the extended release form and the initiation of symptom relief is longer than for the standard form of Sinemet so the patient may need to also take a standard form of the medication in order to get relief for the immediate short term duration.