Treatment of restless legs syndrome with pregabalin: a double-blind,
Author(s): Garcia-Borreguero D, Larrosa O, Williams AM, Albares J, Pascual M, Palacios JC,
Affiliation(s): Sleep Research Institute, Madrid, Spain. firstname.lastname@example.org
Publication date & source: 2010, Neurology. , 74(23):1897-904
OBJECTIVES: To assess the therapeutic efficacy, required dose, and tolerability
of pregabalin in patients with idiopathic restless legs syndrome (RLS).
METHODS: This was a double-blind, placebo-controlled trial with polysomnographic
control, providing Class II evidence. Ninety-eight patients underwent a 2-week
single-blind period with placebo; 58 were randomized to receive pregabalin or
placebo for 12 weeks under a flexible-dose schedule. Endpoints were mean change
from baseline in the International Restless Legs Scale (IRLS) total score,
Clinical Global Impression (CGI), and RLS-6 scales, as well as changes in
periodic limb movements (PLMs) and sleep architecture.
RESULTS: Patients under treatment with pregabalin had a greater improvement in
IRLS score than under placebo (63% vs 38.2%; p < 0.05). The mean effective dose
of pregabalin at the end of treatment was 322.50 mg/day (+/-98.77), although
therapeutic effects were already seen at a mean dose of 139 mg/day. Similarly,
improvements were observed on the CGI, RLS-6 scale, and the Medical Outcomes
Study sleep scale (all p < 0.01) when compared to placebo. Treatment with
pregabalin also resulted in a reduction of the mean (+/-SD) PLM index (p <
0.001). Furthermore, there was a marked improvement in sleep architecture with an
increase in slow wave sleep (p < 0.01), and decreases in wake after sleep onset
and stages 1 and 2 (p < 0.05). Pregabalin was generally well-tolerated. Adverse
events were mild but common, and included unsteadiness, daytime sleepiness, and
CONCLUSIONS: This study shows significant therapeutic effects of pregabalin on
both sensorial and motor symptoms in restless legs syndrome. Treatment with
pregabalin was associated with an improvement of sleep architecture and periodic
limb movements. Adverse events included unsteadiness and sleepiness and should be
screened carefully in the working population, particularly when pregabalin is
administered in the afternoon.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that pregabalin
is effective for the treatment of restless legs syndrome and improves sleep
architecture and periodic limb movements in placebo-unresponsive patients.