Brief CommunicationClinical efficacy of ropinirole for restless legs syndrome is not affected by age at symptom onset
Introduction
Restless legs syndrome (RLS) has been found to have two different phenotypes defined best by age-at-onset [1]. Early-onset RLS, defined as onset before the age of 45 years, has been shown to present with slowly progressing symptoms and high familiality, with an approximately 5-fold increase in risk of disease for first-degree relatives [1]. In contrast, late-onset RLS shows rapid symptom progression, little or no familial link, and appears to be influenced more by environmental than genetic factors [1].
Early-onset RLS shows clearer indications of iron deficiency in the brain, with cerebrospinal fluid (CSF) ferritin showing the most marked decrease for those with the earliest age-at-onset [2], [3]. Another study found that CSF levels of the iron-regulatory hormone, pro-hepcidin, were significantly lower in patients with early-onset RLS, but not in those with late-onset RLS, compared with controls [4]. These studies suggest an abnormality of iron regulation, leading to iron insufficiency in regions of the brain in patients with early-onset RLS, that has been confirmed in autopsy studies of early-onset RLS [5]. Patients with late-onset RLS may represent a more diverse pattern of abnormalities.
Given the differences in underlying pathology for early- versus late-onset RLS, an important question is whether or not these phenotypes also differ in treatment responses to dopamine agonists. If the treatment effects do not differ, then it could be argued that despite putative differences in etiology, RLS phenotypes share a common sensitivity to the status of the dopamine system, altering and presumably causing RLS symptoms. The analyses presented here aim to determine whether the clinical response to the dopamine agonist ropinirole – the first United States Food and Drug Administration-approved treatment for moderate-to-severe RLS – depends upon the age-at-onset of RLS symptoms.
Section snippets
Methods
Four 12-week, randomized, double-blind, placebo-controlled studies (RESET PLM, TREAT RLS 1, 2 and TREAT RLS US: protocols 101468/191, 190, 194 and 249) [6], [7], [8], [9] assessed the efficacy and safety of ropinirole in patients with primary RLS.
Patients had a baseline score of at least 15 points on the International Restless Legs Syndrome Study Group (IRLSSG) rating scale (the International Restless Legs Scale [IRLS]) [10]; and at least 15 nights of RLS symptoms during the previous month.
In
Results
Patient demographics (age, age-at-onset, sex and IRLS total score at baseline) within the pooled data set were similar for the ropinirole (n = 496) and placebo (n = 500) groups (Table 1). No relationship was observed between the age-at-onset of RLS symptoms and the baseline IRLS total score, correlation r = −0.06. Mean (standard deviation [SD]) IRLS total score was similar between the two subgroups: <35 years, 23.6 (5.4) points; ⩾35 years, 23.3 (5.7) points. In addition, there was no evidence that
Discussion
The exploration of pooled data from four 12-week pivotal efficacy studies illustrates that the clinical response to ropinirole was not related to the patient-recalled age-at-onset of RLS symptoms. Similarly, the dose of ropinirole after 12 weeks of treatment did not appear to be related to the age-at-onset.
In the literature, the critical onset age for defining RLS phenotypes varies across studies from 26–45 years, probably reflecting different methods for identifying patients and for
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Restless Legs Syndrome/Willis-Ekbom Disease and Growing Pains in Children and Adolescents
2015, Sleep Medicine ClinicsCitation Excerpt :In addition, resolution of parasomnia was reported in children with RLS and parasomnia following treatment with dopaminergic medications.78 One study has shown that clinical efficacy of ropinirole in patients with RLS is not affected by the age of onset, suggesting that the early- and late-onset phenotypes of RLS share a common responsiveness to dopamine agonists.87 Side effects of dopaminergic medications include nasal congestion, nausea, vomiting, insomnia, daytime sleepiness, fluid retention, hallucination, obsessive compulsive behavior, and augmentation.
Pediatric Sleep Pharmacology: A Primer
2015, Seminars in Pediatric NeurologyCitation Excerpt :There are 3 selective dopamine agonists used for RLS: pramipexole, ropinirole, and rotigotine.30 Although all 3 are approved for RLS treatment in adults, there are no pediatric indications at this time.31-35 These medications have similar side effects to those of levodopa and carbidopa, but they occur less frequently.
Pediatric Sleep Pharmacology
2012, Child and Adolescent Psychiatric Clinics of North AmericaCitation Excerpt :Pramipexole and ropinirole are the most commonly used medications in this category.94 Pramipexole and ropinirole are both FDA approved for the treatment of RLS in adults.97–99 Selective dopaminergic agonists have similar side effects to carbidopa/levodopa but at a lower frequency.
Restless Legs Syndrome
2010, Blue Books of NeurologyCitation Excerpt :The best strategy is to start pharmacological therapy cautiously and at the lowest recommended dosage. RLS and its chronic sleep disturbance may have a significant impact on sleep, social life, and working life,7,223,224 and adequate treatment should not be withheld from patients in need. Pharmacological intervention in RLS is symptomatic and can relieve subjective symptoms or improve the sleep disturbance or both.
Restless legs syndrome among the elderly
2009, International Journal of GerontologyEffects of rotigotine on clinical symptoms, quality of life and sleep hygiene adequacy in hemodialysis-associated restless legs syndrome
2018, NefrologiaCitation Excerpt :Its main advantage, compared to the classic use of levodopa and gabapentin, lies mainly in the occurrence of fewer gastrointestinal adverse events. The most commonly used are pramipexole, ropinirole and, more recently, rotigotine.16–18 Rotigotine shows a better control of symptoms, less incidence of both adverse effects and paradoxical potentiation of symptoms (augmentation effect) as well as an ease administration and dosing to the HD patient.18