First night efficacy of pramipexole in restless legs syndrome and periodic leg movements

Objective: Restless legs syndrome (RLS) seems to improve immediately after a single dose of dopamine-agonists (DA). The aim of the present study was to investigate the acute effects of a low standard dose of pramipexole in RLS drug-naive patients. Methods: A single-blind placebo-controlled study in 32 consecutive idiopathic RLS de-novo patients was carried out. Patients who met the standard criteria for RLS, with a PLMS index greater than 10 as well as an RLS rating scale score greater than 20 underwent clinical and neurophysiological evaluation, hematological screening and two consecutive full-night polysomnographies. On the second night, all patients received 0.25 mg of pramipexole or placebo at 9:00 p.m. Acute symptom response was assessed by a visual analogical scale (VAS). Results: Eighteen patients received pramipexole and 14 patients received placebo. Compared to placebo, the single low dose (0.25 mg) of pramipexole significantly improved RLS symptoms (VAS: from 7.4 +/- 1.68 to 1.3 +/- 1.62, p < 0.00001) and strongly reduced PLMS index (from 45.8 +/- 33.56 to 9.4 +/- 11.40, p < 0.0002). A significant increase in the percentage of stage 2 non-rapid eye movement (NREM) sleep was also observed in the pramipexole group (from 38.7 +/- 10.50 to 50.6 +/- 12.13 p < 0.02). Conclusions: A low dose of pramipexole was effective in treatment-naive patients with RLS from the first night of administration. These results support a direct involvement of the dopaminergic system in RLS pathogenesis and might have important implications for a possible future pramipexole administration on-demand, as well as for a pharmacological test to confirm diagnosis in clinically complex cases. (C) 2006 Elsevier B.V. All rights reserved.