Management of augmentation in restless legs syndrome with pramipexole extended-release

Abstract

Introduction Dopamine agonists represent the first- line treatment in restless legs syndrome (RLS), however in the long term, a substantial portion of patients will develop augmentation, which is a severe drug-related exacerbation of symptoms and the main reason of late therapy withdrawal. The mechanism underlining augmentation is unknown and no guidelines are available to treat it. Objective of the study was to evaluate the role of extended release dopaminoagonist in the management of augmentation. Materials and methods Twenty-four consecutive RLS outpatients (10M,14F, mean age 68.4 ± 10yrs) treated with immediate- release dopamine agonists (pramipexole 11 pts, ropinirole 7 pts, cabergoline 1 pts, levodopa 1 pts, combined DA treatment 4 pts) for a mean period of 6.7yrs ± 5 were diagnosed as affected by severe, clinically relevant augmentation Since an inverse relationship between DA half-life and augmentation has been postulated we decided to switch the treatment to the long-acting extended release (ER) formula of pramipexole, given at 5pm and progressively increased until a satisfactory control of the symptoms was achieved (at a mean dose of 0.75mg, range 0.375–1.125mg), accompanied by a complete withdrawal of the otherdopaminergic agents. Results Resolution of augmentation was observed in all patients in 2–3weeks and persisted so far for a mean follow- up interval of 7months. Mean dose of dopamine agonist was not significanty different before and after the shift of therapy (pramipexole equivalent dosage during augmentation 0.84mg ± 0.51 vs. extended release pramipexole 0.67mg ± 0.28). RLS severity scale decreased from 32 ± 4 to 16 ± 9 ( p Conclusion Pramipexole extended release might represent an easy, safe and fast pharmacological option that needs to be evaluated with prospective and controlled investigations. The findings support the hypothesis that the duration of action of the drug plays a key role in the mechanism of augmentation.