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Levodopa is generally well tolerated in patients with restless legs syndrome and does not cause side effects such as dyskinesia which is felt when it is taken for other conditions (e.g., Parkinson's disease). Prolonged use does not appear to cause toxicity. Some patients can take levodopa for 5-10 years with minimal side effects - whereas patients with Parkinson's disease often experience side effects from Sinemet such as involuntary movements and psychiatric problems.

Daytime augmentation is very common side effect and is reported in up to 80% of patients taking levodopa. Up to 50% of patients who experience augmentation must change medications. It has been noted that augmentation is more likely to occur with higher doses of levodopa. As mentioned before, the only other major side effect early morning rebound which occurs in approximately 20-35% of patients on levodopa treatment. For this reason, many physicians prefer to prescribe dopamine agonists as they have a longer half-life and fewer problems with augmentation and rebound.

Dopamine Agonists

Dopamine agonists act like dopamine and produce dopamine-like effects. Dopamine agonists are usually selected as the first-line treatment for idiopathic restless legs syndrome and have been found to produce significant improvements in restless legs syndrome symptoms in randomized, controlled clinical trials. They are particularly effective when used for advanced restless legs syndrome. Dopamine agonists are much slower acting than levodopa and are taken up to 2 hours before symptoms would typically develop, however, they also are effective for a longer period of time.

When taken at night, 1-2 hours before bedtime, dopamine agonists relieve motor and sensory symptoms until the morning so that sleep quality is significantly improved. If symptoms of restless legs syndrome intensify in the first two years of treatment with dopamine agonists, then it may be due to the progression of restless legs syndrome or to augmentation. This must be evaluated carefully. Augmentation is thought to occur in approximately 20-30% of patients being treated with dopamine agonists and is often milder than for levodopa.

In general, side effects of dopamine agonists include:

• Insomnia
• Nasal congestion
• Bloating
• Edema (swelling) of hands and feet
• Nausea/vomiting
• Chest pain
• Mild augmentation

When dopamine agonists are discontinued, the patient typically shows signs of withdrawal where symptoms intensify for up to 48 hours and then return to baseline levels after 4-7 days. The intensity of withdrawal symptoms is related to the duration of drug use and the dose.

Examples of dopamine agonists that may be used for the treatment of restless legs syndrome include:

• Pergolide mesylate (Permax) - This medication was considered to be a first line treatment for moderate or severe restless legs syndrome. In March 2007, however, the FDA notified healthcare professionals and patients that pergolide has been withdrawn from the market because it has been linked to serious damage to heart valves.

• Pramipexole (Mirapex) - Pramipexole is effective in individuals who do not respond to other dopamine agonists. It is initiated at low doses which are increased up to the point of maximum effectiveness. Pramipexole is taken with food. Benefits of pramipexole include: