Rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome: A randomized, placebo-controlled polysomnographic study

Oertel, Wolfgang H.; Beneŝ, Heike; Garcı́a-Borreguero, Diego; Högl, Birgit; Poewe, Werner; Montagna, Pasquale; Ferini‐Strambi, Luigi; Sixel‐Döring, Friederike; Trenkwalder, Claudia; Partinen, Markku; Saletu, B.; Polo, Olli; Fichtner, Andreas; Schollmayer, Erwin; Kohnen, Ralf; Cassel, Werner; Penzel, Thomas; Stiasny‐Kolster, Karin

doi:10.1016/j.sleep.2010.02.014

Cited by 86 publications

(93 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As mentioned earlier, standardized differences in mean sleep change scores from baseline between treated and control patients were not significantly influenced by trial duration (Table 2). This observation is consistent with the temporal response dynamics of RLS severity scores observed in the drug trials included in the meta-analysis data [43][44][45][46][47][48][49][50][51][52][53][54][55] and is exemplified by data from a 26-week pramipexole trial reported by Hogl et al ( Figure 5), 65 which show consistent superiority of drug treatment over placebo beginning at the first week of treatment and extending to week 26. Thus, inclusion of trials of different duration in the current meta-analysis is justified because there is no meaningful change in the difference between treated and control subjects from week 1 to week 26.…”

Section: Limitationssupporting

confidence: 85%

“…Summary data from 12 of these drug trials were obtained from the peer-reviewed articles, with some supplementary data from manufacturers' websites. [43][44][45][46][47][48][49][50][51][52][53][54] Data for the remaining trial was available only on the manufacturer's website. 55 Description of selected trials receiving investigational treatment and 1645 controls.…”

Section: Trial Selection and Flow Diagrammentioning

confidence: 99%

“…All trials were randomized, concurrent, parallel, prospective, and double-blind, and included patients with at least moderately severe primary RLS. [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] Patients were between 18-79 years old, with symptoms limited to the legs.…”

Section: Trial Selection and Flow Diagrammentioning

confidence: 99%

See 2 more Smart Citations

Improving sleep for patients with restless legs syndrome. Part II: meta-analysis of vibration therapy and drugs approved by the FDA for treatment of restless legs syndrome

Burbank¹,

Buchfuhrer²,

Kopjar³

et al. 2013

JPRLS

View full text Add to dashboard Cite

Background: Vibratory stimulation pads have been shown to improve sleep in patients with restless legs syndrome (RLS) to a greater extent than sham therapy. The current gold standard of treatment is drugs approved by the US Food and Drug Administration (FDA) for use in RLS. The aim of this meta-analysis was to compare the efficacy and safety of vibratory stimulation pads, sham pads, and drugs approved by the FDA for use in RLS. Methods: We searched the PubMed, Embase, and clinical trial websites to identify the relevant randomized, double-blind, and placebo-controlled or sham-controlled studies. Fifteen studies including a combined total of 3455 patients with at least moderately severe primary RLS met our search criteria. Efficacy was defined as the standardized mean difference in sleep improvement between treatment and controls. Safety was assessed by comparing the odds ratios of any adverse events and adverse events leading to study withdrawal between treatment and control subjects. Results: Improvement in Medical Outcomes Study (MOS) sleep inventory scores from baseline was significantly greater in patients treated with vibratory stimulation pads than in those receiving sham pads (Hedges's g, standardized mean difference −0.39, P # 0.02). There was no difference in improvement in sleep scores between patients treated with vibratory stimulation pads (−0.39) and those receiving an approved RLS drug (−0.44, P . 0.70). The risk of any adverse event or withdrawal because of an adverse event was not significantly different between patients treated with vibratory stimulation pads and those assigned to sham pads (Mantel-Haenszel odds ratio 2.16 [P . 0.14] and 1.39 [P . 0.80], respectively). The odds ratios for patients reporting any adverse events and adverse events leading to withdrawal were not significantly different between patients treated with vibratory stimulation pads (2.16 and 1.39, respectively) and those who received approved RLS drugs (2.11 [P . 0.89] and 2.07 [P . 0.82], respectively, mixed-effects model). Conclusion: For patients with moderately severe RLS, vibratory stimulation pads were more effective than sham pads for improving sleep, as effective as FDA-approved RLS drugs, and as safe as both sham pads and FDA-approved RLS drugs.

show abstract

Section: Limitationssupporting

confidence: 85%

Section: Trial Selection and Flow Diagrammentioning

confidence: 99%

See 1 more Smart Citation

Improving sleep for patients with restless legs syndrome. Part II: meta-analysis of vibration therapy and drugs approved by the FDA for treatment of restless legs syndrome

Burbank¹,

Buchfuhrer²,

Kopjar³

et al. 2013

JPRLS

View full text Add to dashboard Cite

show abstract

“…3 Untreated subjects with RLS who have no other sleep disorders (e.g., sleep apnea) have not been found in any clinical study to have a problem falling asleep while driving nor do they show the degree of frontal lobe cognitive deficits expected from their sleep loss. 4 Dopaminergic treatments provide effective treatment for RLS symptoms and dramatically reduce PLMS but in most studies fail to significantly reduce the sleep loss, arousals during sleep, [5][6][7] and abnormal cycling alternating pattern of sleep occurring with RLS. 8 Dopaminergic systems do not appear to be primary for producing the RLS sleep/wake arousal.…”

Section: Discussionmentioning

confidence: 99%

Thalamic glutamate/glutamine in restless legs syndrome

et al. 2013

View full text Add to dashboard Cite

Objective: To evaluate possible abnormal increase in thalamic glutamate/glutamine levels for restless legs syndrome (RLS) indicating increased glutamatergic activity producing arousal that at night disrupts and shortens sleep. Methods:1 H MRS of the right thalamus was performed using a 1.5 T GE MRI scanner and the PROBE-P (PRESS) on 28 patients with RLS and 20 matched controls. The Glx signal (combination of mostly glutamate [Glu] and glutamine [Gln]) was assessed as a ratio to the total creatine (Cr). This study tested 2 primary hypotheses: 1) higher thalamic Glx/Cr for patients with RLS than controls; 2) thalamic Glx/Cr correlates with increased wake during the sleep period.Results: The Glx/Cr was higher for patients with RLS than controls (mean 6 SD 1.20 6 0.73 vs 0.80 6 0.39, t 5 2.2, p 5 0.016) and correlated significantly with the wake time during the sleep period (r 5 0.61, p 5 0.007) and all other RLS-related polysomnographic sleep variables (p , 0.05) except for periodic leg movements during sleep (PLMS)/hour. Conclusions:The primary findings introduce 2 new related dimensions to RLS: abnormalities in a major nondopaminergic neurologic system and the arousal disturbance of sleep. The strong relation of the arousal sleep disturbance to glutamate and the lack of relation to the PLMS motor features of RLS contrasts with the reverse for dopamine of a limited relation to arousal sleep disturbance but strong relation to PLMS. Understanding this dichotomy and the interaction of these 2 differing systems may be important for understanding RLS neurobiology and developing better treatments for RLS. Neurology 1 H MRS 5 proton magnetic resonance spectroscopy; mI 5 myo-inositol; NAA 5 N-acetylaspartate; PLMS 5 periodic leg movements during sleep; PSG 5 polysomnography; RLS 5 restless legs syndrome; SWS 5 slow-wave sleep; VMB 5 ventral midbrain; WDSP 5 wake during the sleep period.Restless legs syndrome (RLS) is a rest-induced, movement-responsive, mostly nocturnal, urge to move the legs commonly associated with periodic leg movements during sleep (PLMS).1 Sleep disruption is the primary factor producing most of the morbidity of moderate to severe RLS. 2Patients with RLS, however, rarely report problems with excessive daytime sleep despite total sleep times averaging less than 5.5 hours.3 Untreated subjects with RLS who have no other sleep disorders (e.g., sleep apnea) have not been found in any clinical study to have a problem falling asleep while driving nor do they show the degree of frontal lobe cognitive deficits expected from their sleep loss. 4 Dopaminergic treatments provide effective treatment for RLS symptoms and dramatically reduce PLMS but in most studies fail to significantly reduce the sleep loss, arousals during sleep, 5-7 and abnormal cycling alternating pattern of sleep occurring with RLS. 8 Dopaminergic systems do not appear to be primary for producing the RLS sleep/wake arousal.If not dopamine, then what produces this RLS arousal pattern? A review of potential nondopaminergic systems led t...

show abstract

“…It is highly likely that the rotigotine patch improves RLS symptoms as measured by the IRLS (2 Class I 26,27 and 3 Class II studies, [28][29][30] up to 6 months in duration). It is likely that rotigotine improves PLMS (1 Class I study 27 ), but there is insufficient evidence to support or refute an effect on other objective sleep measures (1 Class I study 27 that is not statistically significant but whose CIs include clinically important effects). It is likely that rotigotine improves sleep disturbance and subjective sleep quantity (meta-analysis of 1 Class I 27 and 2 Class II studies, 28,30 with 1 of the Class II studies achieving statistical significance on its own 30 and the other Class I and Class II studies achieving statistical significance together).…”

mentioning

confidence: 99%