Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study.
OBJECTIVE
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 headache.


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.


METHODS
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.
Garcia-Borreguero
D
D
Sleep Research Institute, Madrid, Spain. dgb@iis.es
Larrosa
O
O
Williams
A-M
AM
Albares
J
J
Pascual
M
M
Palacios
J C
JC
Fernandez
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use*; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005121:Extremities / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects; D017286:Polysomnography / Q000379:methods; D000069583:Pregabalin; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid