Rotigotine in the treatment of primary restless legs syndrome: A meta-analysis of randomized placebo-controlled trials

Abstract

The aim of this study was to summarize the efficacy and tolerability of rotigotine in the treatment of primary restless legs syndrome (RLS). PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for English-language randomized controlled trials (RCTs) that assessed the effectiveness of rotigotine for RLS. The pooled mean change from baseline in International RLS (IRLS) Study Group Rating Scalescore and relative risk (RR) of response based on the Clinical Global Impression-Improvement (CGI-I) scale score were applied to evaluate the outcomes. The pooled proportions of adverse events (AEs) were also estimated. Six RCTs were included. The meta-analysis showed a favorable effectiveness of rotigotine versus placebo on RLS [mean change on IRLS score: mean difference (MD)=−4.80; 95% confidence interval (CI): −5.90 to −3.70; P<0.00001 and RR of response on CGI-I was 2.19; 95% CI: 1.86 to 2.58, P<0.00001]. The most common AEs were application site reactions, nausea, headache and fatigue. In general, rotigotine was well-tolerated in patients with primary RLS. Based on the findings from the meta-analysis, rotigotine was more significantly efficacious in the treatment of RLS than placebo. Nevertheless, long-term studies and more evidence of comparisons of rotigotine with other dopamine agonists are needed.

Keywords

restless legs syndrome / rotigotine / dopamine agonist

References

[1] TrenkwalderC, PaulusW, WaltersAS. The restless legs syndrome. Lancet Neurol, 2005, 4(8): 465-475 PMID: 16033689

[2] AllenRP, PicchiettiD, HeningWA, et al. . Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med, 2003, 4(2): 101-119 PMID: 14592341

[3] ZucconiM, Ferini-StrambiL. Epidemiology and clinical findings of restless legs syndrome. Sleep Med, 2004, 5(3): 293-299 PMID: 15165538

[4] OhayonMM, O’HaraR, VitielloMV. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev, 2012, 16(4): 283-295 PMCID: 3204316 PMID: 21795081

[5] NomuraT, InoueY, KusumiM, et al. . Prevalence of restless legs syndrome in a rural community in Japan. Mov Disord, 2008, 23(16): 2363-2369 PMID: 18973260

[6] García-BorregueroD, KohnenR, HöglB, et al. . Validation of the Augmentation Severity Rating Scale (ASRS): A multicentric, prospective study with levodopa on restless legs syndrome. Sleep Med, 2007, 8(5): 455-463 PMID: 17543579

[7] TrenkwalderC, HeningWA, MontagnaP, et al. . Treatment of restless legs syndrome: An evidence-based review and implications for clinical practice. Mov Disord, 2008, 23(16): 2267-2302 PMID: 18925578

[8] Stiasny-KolsterK1, KohnenR, SchollmayerE, et al. . Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord, 2004, 19(12): 1432-1438 PMID: 15390055

[9] OertelWH, BenesH, Garcia-BorregueroD, et al. . Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dosefinding trial in Europe. Sleep Med, 2007, 9(3): 228-239 PMID: 17553743

[10] SwartzMK. The PRISMA statement: a guideline for systematic reviews and meta-analyses. J Pediatr Health Care, 2011, 25(1): 1-2 PMID: 21147401

[11] MulrowCD, OxmanAD. Cochrane Collaboration Handbook, 1996, Oxford, UK, Cochrane Collaboration

[12] WhiteheadA. Meta-Analysis of Controlled Clinical Trials, 2002, Chichester, UK, New York, NY, John Wiley & Sons

[13] TrenkwalderC, BenesH, PoeweW, et al. . Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: A randomised, doubleblind, placebo-controlled trial. Lancet Neurol, 2008, 7(7): 595-604 PMID: 18515185

[14] OertelWH, BenesH, Garcia-BorregueroD, et al. . Efficacy of rotigotine transdermal system in severe restless legs syndrome: A randomized, double-blind, placebocontrolled, six-week dose-finding trial in Europe. Sleep Med, 2008, 9(3): 228-239 PMID: 17553743

[15] OertelWH, BenesH, Garcia-BorregueroD, et al. . Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: A randomized, placebo-controlled polysomnographic study. Sleep Med, 2010, 11(9): 848-856 PMID: 20813583

[16] HeningWA, AllenRP, OndoWG, et al. . Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States. Mov Disord, 2010, 25(11): 1675-1683 PMID: 20629075

[17] InoueY, ShimizuT, HirataK, et al. . Efficacy and safety of rotigotine in Japanese patients with restless legs syndrome: a phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group study. Sleep Med, 2013, 14(11): 1085-1091 PMID: 24055212

[18] ReynoldsNA, WellingtonK, EasthopeSE. Rotigotine in Parkinson’s disease. CNS Drugs, 2005, 19(11): 973-981 PMID: 16268667

[19] Garcia-BorregueroD, AllenRP, KohnenR, et al. . Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute. Sleep Med, 2007, 8(5): 520-530 PMID: 17544323

[20] Collado-SeidelV, KazenwadelJ, WetterTC, et al. . A controlled study of additional SR-Ldopa in L-dopa responsive RLS with late night symptoms. Neurology, 1999, 52(2): 285-290 PMID: 9932945

[21] LeWittPA, NausiedaPA, ChangFL, et al. . Rotigotine transdermal system in a multicenter trial of patients with advanced Parkinson’s disease as adjunctive therapy to levodopa. Neurology, 2006, 66(Suppl2): A184

[22] RascolO, PoeweW, GiladiN, et al. . Rotigotine transdermal patch as adjunctive therapy in comparison to pramipexole. Eur J Neurol, 2006, 13(Suppl2): S321

[23] WinkelmanJW, SethiKD, KushidaCA, et al. . Efficacy and safety of pramipexole in restless legs syndrome. Neurology, 2006, 67(6): 1034-1039 PMID: 16931507

[24] TrenkwalderC, Garcia-BorregueroD, MontagnaP, et al. . Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry, 2004, 75(1): 92-97 PMCID: 1757460 PMID: 14707315

[25] ZucconiM, FerriR, AllenR, et al. . International Restless Legs Syndrome Study Group (IRLSSG). The official World Association of Sleep Medicine (WASM) standards for recording and scoring periodic leg movements in sleep (PLMS) and wakefulness (PLMW) developed in collaboration with a task force from the International Restless Legs Syndrome Study Group (IRLSSG). Sleep Med, 2006, 7(2): 175-183 PMID: 16459136

[26] HornyakM, TrenkwalderC, KohnenR, et al. . Efficacy and safety of dopamine agonists in restless legs syndrome. Sleep Med, 2012, 13(3): 228-236 PMID: 22281001