Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: Results from a multi‐center, randomized, active controlled trial

Abstract

We report the first large-scale double-blind, randomly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome (RLS), the dopamine agonist cabergoline (CAB) and levodopa/benserazide (levodopa). Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks. Efficacy was assessed by changes in the IRLS (International RLS Severity Scale) and by time to discontinuation of treatment due to loss of efficacy or augmentation. 361 of 418 screened patients (age 58 +/- 12 years, 71% females) were randomly assigned and treated (CAB: n = 178; levodopa: n = 183) in 51 centers of four European countries. Baseline IRLS total score was 25.7 +/- 6.8. The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group (d = -6.6, P < 0.0001). More patients in the levodopa group (24.0%) than in the CAB group (11.9%, P = 0.0029, log-rank test) discontinued because of loss of efficacy (14.2% vs. 7.9%, P = 0.0290) or augmentation (9.8% vs. 4.0%, P = 0.0412). Adverse events (AEs) occurred in 83.1% of the CAB group and in 77.6% of the levodopa group. In both groups, most frequent AEs were gastrointestinal symptoms (CAB: 55.6%, levodopa: 30.6%, P < 0.0001). This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy. Tolerability was found more favorable with levodopa than with cabergoline.

Assessment of restless legs syndrome—Methodological approaches for use in practice and clinical trials

“…No total score is defined but the scales are analyzed separately to establish a profile of changes over time and are useful both on weekly and daily (diaries) basis. The RLS-6 scales have been validated in a large trial (n ϭ 361, 15 ) and the evaluation shows moderate correlation between the RLS-6 scales and the IRLS. Sensitivity for placebo effects seems to be lower than for the IRLS or the CGI.…”

“…Psychometric indicators were good to excellent in this study as well in a reanalysis with the data of a large scale clinical trial population. 15 The authors recommend analysis of the profile of the individual items in addition to the total score. The QoL-RLS was applied in several clinical trials; in all these trials, the total score was more improved by active dopamine agonist therapy than by placebo (e.g., Refs.…”

Clinical trials in restless legs syndrome—Recommendations of the European RLS Study Group (EURLSSG)

“…Therefore, placebo-controlled studies should be restricted to 12 weeks, including at least 4 weeks of maintenance treatment. More active comparator trials using dopaminergic 55 or nondopaminergic comparators like opioids should be conducted in the future.…”

Rotigotine Transdermal Patch for the Treatment of Restless Legs Syndrome

“…Several randomized controlled studies showed significant changes if patients were treated with 0.25-6 mg/day of ropinirole for 4-12 weeks (table 4) [38,39,40]. The efficacy of ergot agonists such as cabergoline (2 mg) was demonstrated in studies employing levodopa as the active comparator [41]. Treatment with 0.125-0.75 mg/day of pramipexole was also explored, with positive results [42,43].…”