Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.

This randomized, double-blinded, placebo-controlled trial (NCT00135993) assessed efficacy and safety of the dopamine agonist rotigotine in the treatment of idiopathic restless legs syndrome (RLS) over a 6-month maintenance period. A total of 505 eligible participants with moderate to severe RLS (IRLS sum score >or= 15) were randomly assigned to five groups to receive either placebo or rotigotine (0.5, 1, 2, or 3 mg/24 hr) delivered by once-daily transdermal patch (fixed-dose regimen). The two co-primary efficacy parameters decreased from baseline to end of maintenance in IRLS sum score and in clinical global impressions (CGI-1) score. On both primary measures, 2 and 3 mg/24 hr rotigotine was superior to placebo (P < 0.001). Adjusted treatment differences to placebo for the IRLS sum score were -4.5 (95% CI: -6.9, -2.2) for 2 mg/24 hr rotigotine, -5.2 (95% CI: -7.5, -2.9) for 3 mg/24 hr rotigotine, and for CGI item 1 -0.65 (95% CI: -1.0, -0.3) and -0.9 (95% CI: -1.3, -0.5) for the 2 and 3 mg/24 hr doses, respectively. Skin reactions (27%) and known dopaminergic side effects such as nausea (18.1%) and headache (11.6%) were mostly mild or moderate in rotigotine subjects. Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms. Treatment efficacy was maintained throughout the 6-month double-blind period.

Restless legs syndrome (RLS)/Willis-Ekbom disease (WED) is a common disorder, occurring at least twice a week and causing at least moderate distress in 1.5% to 2.7% of the population. It is important for primary care physicians to be familiar with this disorder and its management. Much has changed in its management since our previous algorithm was published in 2004, including the availability of several new drugs. This revised algorithm was written by members of the Medical Advisory Board of the Willis-Ekbom Disease Syndrome Foundation based on scientific evidence and expert opinion. It considers the management of RLS/WED under intermittent RLS/WED, chronic persistent RLS/WED, and refractory RLS/WED. Nonpharmacological approaches, including mental alerting activities, avoiding substances or medications that may exacerbate RLS, and the role of iron supplementation, are outlined. Chronic persistent RLS/WED should be treated with either a nonergot dopamine agonist or a calcium channel α-2-δ ligand. We discuss the available drugs, the factors determining which to use, and their adverse effects. We define refractory RLS/WED and describe management approaches, including combination therapy and the use of high-potency opioids.

As rated by patients and by clinicians, pramipexole was efficacious and safe in reducing the symptoms of restless legs syndrome.

Objective: To assess the efficacy and tolerability of the nondopaminergic agent XP13512/ GSK1838262 in adults with moderate to severe primary restless legs syndrome (RLS).Methods: Patient Improvements in Vital Outcomes following Treatment in Restless Legs Syndrome I was a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of XP13512 1,200 mg or placebo taken once daily at 5:00 PM with food. Coprimary endpoints were mean change from baseline International Restless Legs Scale (IRLS) total score and proportion of investigator-rated responders (very much improved or much improved on the Clinical Global Impression-Improvement scale) at week 12 (last observation carried forward). Tolerability was assessed using adverse events, vital signs, and clinical laboratory parameters. Results:A total of 222 patients were randomized (XP13512 ϭ 114, placebo ϭ 108) and 192 patients (XP13512 ϭ 100, placebo ϭ 92) completed the study. At week 12, the mean change from baseline IRLS total score was greater with XP13512 (Ϫ13.2) compared with placebo (Ϫ8.8). Analysis of covariance, adjusted for baseline score and pooled site, demonstrated a mean treatment difference of Ϫ4.0 (95% confidence interval [CI], Ϫ6.2 to Ϫ1.9; p ϭ 0.0003). More patients treated with XP13512 (76.1%) were responders compared with placebo (38.9%; adjusted OR 5.1; 95% CI, 2.8 to 9.2; p Ͻ 0.0001). Significant treatment effects for both coprimary measures were identified at week 1, the earliest time point measured. The most commonly reported adverse events were somnolence (XP13512 27%, placebo 7%) and dizziness (XP13512 20%, placebo 5%), which were mild to moderate in intensity and generally remitted.Conclusions: XP13512 1,200 mg, taken once daily, significantly improved restless legs syndrome (RLS) symptoms compared with placebo and was generally well tolerated in adults with moderate to severe primary RLS. Neurology ® 2009;72:439-446 GLOSSARY AE ϭ adverse event; ANCOVA ϭ analysis of covariance; CGI-I ϭ Clinical Global Impression-Improvement; CI ϭ confidence interval; ESS ϭ Epworth Sleepiness Scale; IRLS ϭ International Restless Legs Scale; LOCF ϭ last observation carried forward; LS ϭ least squares; MITT ϭ modified intent-to-treat population; MOS ϭ Medical Outcomes Study; NNT ϭ numbers needed to treat; OR ϭ odds ratio; PghSD ϭ Pittsburgh Sleep Diary; PSQ ϭ post-sleep questionnaire; RLS ϭ restless legs syndrome; RLSQoL ϭ RLS Quality of Life; SAE ϭ serious adverse events; SOS ϭ Sudden Onset of Sleep questionnaire; TST ϭ total sleep time; WASO ϭ wake time after sleep onset.Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an urge to move the legs, usually caused by uncomfortable sensations that begin or worsen at rest and in the evening or at bedtime, and are temporarily relieved by movement. 1 Sleep complaints are common among patients with moderate to severe RLS; approximately 75% of these patients report difficulties with sleep initiation, maintenance, or awakenings. 2 Approximately 2% to 3% of the US population reports RLS...