Efficacy and tolerability of ropinirole in patients with restless legs syndrome and a baseline IRLS total score >= 24 points - data from the ropinirole clinical trial programme
ABSTRACT Results from one of the largest clinical trial programmes to date of a dopamine agonist in patients with primary restless legs syndrome (RLS) have demonstrated that ropinirole, 0.25-4.0 mg once daily 1-3 hours before bedtime, is associated with significant improvements in RLS symptoms, sleep parameters and quality-of-life measures, compared with placebo. Analyses were conducted in a subpopulation of patients with a baseline score on the International Restless Legs Scale (IRLS) of at least 24 points.
Data was pooled from four, 12-week, pivotal studies: RESET PLM and TREAT RLS 1, 2 and US.
Covariate analysis demonstrated that the magnitude of treatment difference between ropinirole and placebo for change in IRLS total score (a measure of RLS symptom severity) increased with increasing baseline IRLS total score. Mean treatment difference was > 3 points in patients with a baseline total score > or = 24. Among this population, ropinirole treatment was associated with significant reduction in RLS symptom severity compared with placebo, along with significant improvements in global symptoms and sleep measures. A treatment benefit was also observed for measures of quality of life. Ropinirole is well tolerated in this patient population.
Patients with primary RLS and baseline IRLS total score > or = 24 gain clinically meaningful benefits from ropinirole treatment. As with the overall population in the ropinirole clinical trial programme, ropinirole was associated with improvements in RLS symptoms, global symptoms, sleep and quality of life and was well tolerated in patients with a baseline IRLS total score > or = 24.
SourceAvailable from: Sharon Tracy[Show abstract] [Hide abstract]
ABSTRACT: A systematic literature review and meta-analyses (where appropriate) were performed to update the previous AASM practice parameters on the treatments, both dopaminergic and other, of RLS and PLMD. A considerable amount of literature has been published since these previous reviews were performed, necessitating an update of the corresponding practice parameters. Therapies with a STANDARD level of recommendation include pramipexole and ropinirole. Therapies with a GUIDELINE level of recommendation include levodopa with dopa decarboxylase inhibitor, opioids, gabapentin enacarbil, and cabergoline (which has additional caveats for use). Therapies with an OPTION level of recommendation include carbamazepine, gabapentin, pregabalin, clonidine, and for patients with low ferritin levels, iron supplementation. The committee recommends a STANDARD AGAINST the use of pergolide because of the risks of heart valve damage. Therapies for RLS secondary to ESRD, neuropathy, and superficial venous insufficiency are discussed. Lastly, therapies for PLMD are reviewed. However, it should be mentioned that because PLMD therapy typically mimics RLS therapy, the primary focus of this review is therapy for idiopathic RLS. CITATION: Aurora RN; Kristo DA; Bista SR; Rowley JA: Zak RS; Casey KR; Lamm CI; Tracy SL; Rosenberg RS. The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses. SLEEP 2012;35(8):1039-1062.Sleep 01/2012; 35(8):1039-62. DOI:10.5665/sleep.1988 · 5.06 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: As with studies of other dopamine agonists, previously reported studies of ropinirole in restless legs syndrome (RLS) recruited patients with baseline International Restless Legs Scale (IRLS) total scores ≥15. The reported pooled analyses of clinical trials data suggest benefits of ropinirole in patients with IRLS total scores ≥24, but the effects of ropinirole have not been prospectively evaluated in this patient population. The goal of this study was to evaluate the efficacy and tolerability of ropinirole in patients with RLS and baseline IRLS total scores ≥24. This study was conducted in part to fulfill a postlicensing commitment between the maker of ropinirole and the European Union's Committee for Medicinal Products for Human Use. The protocol for this study comprised a randomized, double-blind, placebo-controlled, parallel-group, 26-week phase during which adults with baseline IRLS total scores ≥24 received a ropinirole dose from 0.25 to 4 mg (n = 197) or placebo (n = 207) followed by a 40-week, open-label phase during which all patients (n = 269) received ropinirole. The primary efficacy end point was the change from baseline in the IRLS total score at week 12. Tolerability measures included the incidence of adverse events, augmentation, and early morning rebound. Due to the possibility of a treatment-by-center group interaction (P = 0.04) in the IRLS analysis, further efficacy exploratory analyses were performed to assess the impact of the interaction on the overall assessment of efficacy. Demographic characteristics were comparable between groups (mean [SD] age: placebo, 56.1 [11.38] years; ropinirole, 56.5 [11.92] years; 63% female in both groups). All of the patients in the ropinirole group were white; 99% of the placebo group was white. Ropinirole was significantly better than placebo for change from baseline in the IRLS total score during both short- and long-term treatment, with mean treatment differences of -2.1 (P = 0.039) and -2.5 (P = 0.023) for weeks 12 and 26, respectively. A statistically significant treatment by center group interaction was observed (P = 0.040) for the change from baseline in IRLS total score, indicating variation of treatment effects among center groups; however, all center groups showed an improvement from baseline at both week 12 and week 26 for the ropinirole immediate-release group and the placebo group. The incidences of augmentation and early morning rebound were ≤4% for ropinirole. The adverse event profile of ropinirole was consistent with that reported in previous clinical trials. In this subset of patients with RLS and a baseline IRLS total score ≥24, ropinirole was effective and well tolerated compared with placebo. The incidence of augmentation and early morning rebound in this study was low. Clinicaltrials.gov identifier: NCT00329602.Clinical Therapeutics 08/2013; DOI:10.1016/j.clinthera.2013.06.016 · 2.59 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Restless legs syndrome/Willis Ekbom disease (RLS/WED) has been recognized as a significant medical disorder since the 17th century. It was studied mostly in the last 50 years in relation to increasing interest in sleep medicine and health-related quality of life. This led to recognition that the disease is not well characterized as restless feelings in the legs. These symptoms are reported in many situations, but the subjective experience of RLS/WED patients differs from that experienced by others. Thus a new name has been introduced that avoids problems of symptom definition of a disease by naming it after those who first characterized it, i.e. ‘Willis Ekbom disease’. This article emphasizes the importance of RLS/WED for psychiatry. The disease carries significant increased risk for depression and anxiety disorders. Treatment requires consideration of these co-morbid disorders. RLS/WED can exacerbate or even engender psychiatric disease, so treatment of psychiatric disease should also include consideration of RLS/WED. The need for attention to RLS/WED is particularly significant for depression. Most anti-depressants exacerbate or can even engender RLS/WED. Thus this article seeks to introduce RLS/WED in relation to psychiatric practice. It presents the RLS/WED disease, its overlap with psychiatry and the current treatment options.International Review of Psychiatry 06/2014; 26(2). DOI:10.3109/09540261.2014.904279 · 1.80 Impact Factor