Restless Leg Syndrome Equally Responsive to Multiple Drug Classes

woman rubbing painful leg
woman rubbing painful leg
Few head-to-head trials have been conducted that have compared different classes of drugs for treatment of RLS.

The dopaminergic medication rotigotine and the α-2-δ ligands gabapentin enacarbil and pregabalin provide similar treatment effects for patients with restless leg syndrome, according to a meta-analysis published in the European Journal of Neurology.

A network meta-analysis of published randomized controlled trials was performed to determine differences in treatment-related effects among pramipexole, ropinirole, rotigotine, gabapentin enacarbil, and pregabalin for the treatment of restless leg syndrome. The investigators assessed mean score changes using the International Restless Leg Syndrome Study Group Rating Scale (IRLS) as well as the Clinical Global Impressions-Improvement (CGI-I) scale.

A total of 35 studies of patients with restless leg syndrome (n=7333) were included. Among these studies, gabapentin enacarbil as well as pregabalin and rotigotine demonstrated greater benefit than placebo (mean reduction in IRLS scores: -5.31 [-6.74 to -3.87], -5.20 [-6.91 to -3.49], and 5.17 [3.73 to 6.61], respectively).

Nausea and headache were among the most common adverse effects associated with rotigotine, but no statistically significant intertreatment differences between the drug classes with regard to incidence of nausea or headache were found.

The investigators performed another network meta-analysis consisting of 24 studies and 5137 patients. In this analysis, researchers found that gabapentin enacarbil and rotigotine correlated with higher CGI-I response rates (odds ratio: 5.68; 95% CI, 4.14-7.21 and 4.68; 95% CI, 2.87-6.49) than placebo; however, there were no intertreatment differences observed among gabapentin enacarbil, pramipexole, pregabalin, or rotigotine.

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The investigators noted that the lack of an analysis of other restless leg syndrome treatments, such as iron replacement, gabapentin, and nonpharmacologic therapies, represented a limitation of this study. Additionally, the IRLS and CGI scales are subjective in nature and may not be truly representative of this patient population at large.

“Our network meta-analysis adds to the current body of evidence by allowing direct comparisons of efficacy for dopamine agonists and alpha-2-ligands,” said the study’s lead investigator Imran H. Iftikhar, MD, “revealing important differences for gabapentin enacarbil and rotigotine and also showing important differences in the side effect profiles of different drug classes.”


Iftikhar IH, Alghothani L, Trotti LM. Gabapentin enacarbil, pregabalin and rotigotine are equally effective in restless legs syndrome: a comparative meta-analysis [published online September 9, 2017]. Eur J Neurol. doi: 10.1111/ene.13449