Pramipexole: new use for an old drug – the potential use of pramipexole in the treatment of restless legs syndrome

Restless legs syndrome (RLS) is characterized by paraesthesias–dysesthesias and motor restlessness worsening at rest–in the evening, with at least temporary relief by activity. Its etiology is unknown, though it could be secondary to various conditions. It is well known, however, that dopamine plays a crucial role in the pathophysiology of RLS, as dopaminergic agonists achieve marked improvement. Pramipexole is a nonergoline compound with selectivity for D3 dopamine receptors. This drug is very effective in the treatment of idiopathic and secondary RLS and in treatment-resistant patients, as shown by double-blind, placebo-controlled studies in adults. In children, studies are much more limited, and RLS is often misdiagnosed as “growing pain” or attention deficit hyperactivity disorder. Pramipexole has been successful in open studies, eliminating clinical symptoms. This medication has the advantage of being free of the frequently encountered problems seen with ergot derivatives. The side-effects are limited, particularly at the dosages usually prescribed for RLS treatment: They are much lower than in Parkinson’s disease, and inappropriate sleepiness and sleep attacks, particularly while driving, or compulsive behavior have not been seen. Compared with the adverse reactions of levodopa, including tolerance, rebound, and augmentation phenomena in RLS, which led to usage of dopamine agonists as first line of treatment for RLS, pramipexole has had one of the best profiles. Augmentation can still be noted with the drug, but after longer usage time compared with many other dopamine agonists. Although excessive daytime sleepiness has been noted, sleep attacks have not been encountered in RLS patients treated with pramipexole.