Drug Treatment Available for Patients With Severe Restless Legs Syndrome

Levodopa Drug of First Choice

Dopaminergic drugs, in particular levodopa, are currently the treatment of first choice for idiopathic or uraemic RLS.^[1] Levodopa itself is always given with a dopa decarboxylase inhibitor (DDCI) such as carbidopa or benserazide, and its efficacy has been verified in a number of nonblind and controlled trials.^[1]

In most of the studies investigating the efficacy of levodopa in RLS, patients received levodopa 50 to 250mg as a single dose 1 hour before bedtime.^[1] Subjective improvement of sleep quality was reported consistently, and polysomnographic studies showed suppression of periodic limb movements in sleep (PLMS).^[10,11] Therapeutic efficacy has been shown to be sustained for at least 2 years.^[12]

The benefit of regular release formulations of levodopa appears to last for about 4 hours, and a combination of one of these with a sustained-release formulation may help patients with symptoms beyond this period. Sustained-release preparations given alone tend not to be helpful, because effective peak plasma concentrations of levodopa are not attained before the patient falls asleep. Some patients who develop daytime paraesthesias and restlessness require additional doses during the day.^[1,2] Levodopa treatment is tolerated well by most patients: dyskinesias such as those seen in patients with Parkinson's disease have never been reported in patients with RLS. Altered patterns of severity ('time shift' or 'augmentation') or 'rebound' of symptoms may be managed by manipulation of dose timing and/or formulation prescribed. Occasionally, dosage reductions or changes in medication are required.

Bromocriptine (primarily a dopamine D₂ receptor agonist) and pergolide (a combined D₁ and D₂ agonist) improve both subjective sleep quality and PLMS in patients with RLS.^[1] To avoid adverse effects, treatment should be started with low dosages that are increased with caution over 1 to 2 weeks. The new non-ergot dopamine agonist pramipexole^† has also been associated with improvements in symptoms of RLS, and preliminary data suggest that cabergoline and ropinirole may also be useful.^[1] Unlike levodopa, however, these agents are not suitable for use on an as-needed basis, although levodopa can be added to therapy with another dopamine agonist if necessary.^[1]

© 2000 Adis Data Information BV

Cite this: Drug Treatment Available for Patients With Severe Restless Legs Syndrome - Medscape - Jun 19, 2000.