Increased Blood Pressure Dipping in Restless Legs Syndrome With Rotigotine: A Randomized Trial

Abstract

The objective of this study was to assess the rotigotine effect on the nocturnal blood pressure (BP) dip by 24-hour ambulatory BP monitoring and on endothelial function in patients with restless legs syndrome (RLS) compared with placebo. Methods: In this double-blind, placebo-controlled trial, 76 adult patients with moderate to severe RLS and periodic legs movements in sleep index ≥10/hour were randomized to rotigotine at optimal dose of 3 mg per day or placebo for 6 weeks. A total of 6 patients had a major protocol deviation. Polysomnography, ambulatory BP monitoring, and endothelial function were assessed at baseline and end point. The primary outcome was the between-group difference in the percentage of BP nondipper profiles at end point. The main secondary outcomes were the mean BP dip, periodic legs movements in sleep index, and endothelial function. Results: Of the 70 patients (age, 59.4 ± 11.40; 43 women) randomized to rotigotine (n = 34) and placebo (n = 36), 66 (33 rotigotine, 33 placebo) completed the study. The percentage of BP nondippers at end point was higher in the placebo than in the rotigotine group (systolic BP, 72.22% vs 47.06%; diastolic BP, 47.22% vs 20.59%; P < 0.05). Mean BP dip at end point was higher in the rotigotine than in the placebo group (systolic BP, 11.24 ± 6.15 vs 6.12 ± 7.98; diastolic BP, 15.12 ± 7.09 vs 9.36 ± 10.23; P < 0.05). Endothelial function was comparable between the groups. No significant safety concerns were reported with similar incidences of adverse events between groups. Conclusion: Rotigotine increased the percentage of BP dipper profiles and the BP dip in patients with RLS. Future studies should assess whether this change is associated with a reduction in the long-term cardiovascular risk in RLS.

Sleep related movement disorders in the elderly: a review of recent literature

“…Several studies have demonstrated an association between RLS and frontal-executive dysfunction, reduced cognitive flexibility, and reduced attention, while others have shown no association between RLS and cognition (Gao et al, 2021). However, a metanalysis demonstrated a negative association between RLS severity and global cognitive function, as measured by the Minimental status exam or MoCA (Chenini et al, 2020), and in another study of patients with an average age of 56, attention was agitated, as measured by the Stroop test or Trails making B test (Jung, 2015). Furthermore, a recent retrospective cohort study of over 2,500 people over 60 years old with up to 12 years of follow-up showed a 1.74 times increased risk of all-cause dementia in people with RLS and a higher risk of developing vascular dementia over Alzheimer's dementia (Xu et al, 2022).…”

Exploration of restless legs syndrome under the new concept: A review

“…Rotigotine (Neupro) patches can provide patients with round-the-clock symptom control because of their continuous, progressive, all-day release. [ 65 ] This extended duration of action and sustained release of dopamine into the blood may minimize dopamine fluctuations at the receptor and may be associated with a low propensity to evolve into potentiation syndrome. [ 65 ] The dose of rotigotine can be started at a patch strength of 1.0 mg and increased weekly to a maximum daily dose of 2.0 or 3.0 mg. [ 66 ] Clinical trials of rotigotine have shown that a further dose increase to 4.0 mg per day could be considered, but this high dose may carry a greater risk of enhancement.…”

“…[ 65 ] This extended duration of action and sustained release of dopamine into the blood may minimize dopamine fluctuations at the receptor and may be associated with a low propensity to evolve into potentiation syndrome. [ 65 ] The dose of rotigotine can be started at a patch strength of 1.0 mg and increased weekly to a maximum daily dose of 2.0 or 3.0 mg. [ 66 ] Clinical trials of rotigotine have shown that a further dose increase to 4.0 mg per day could be considered, but this high dose may carry a greater risk of enhancement. [ 67 ] Rotigotine, as a transdermal patch, may cause skin reactions, such as excessive itching or redness of the skin at the application site.…”