Improvement Of Restless Legs Syndrome Symptoms Research Articles

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Treatment of restless legs syndrome/Willis-Ekbom disease with the non-selective ENT1/ENT2 inhibitor dipyridamole: testing the adenosine hypothesis

ObjectivesRecent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum and cortex. We hypothesized that an increase in extracellular adenosine induced by inhibitors of adenosine transporters, such as the non-selective ENT1/ENT2 inhibitor dipyridamole, would result in an improvement in RLS symptoms. MethodsIn a prospective two-month open-label, non-placebo controlled clinical trial, 15 untreated idiopathic RLS patients began treatment with 100 mg dipyridamole (with uptitration to 400 mg if necessary). Multiple Suggested Immobilization Tests and polysomnography were performed at baseline and at eight weeks. Severity was assessed at four and eight weeks using the IRLS, and the CGI scales. The primary endpoint was therapeutic response (50% improvement in IRLS total score). ResultsThirteen patients completed the study. IRLS score improved from a mean (±S.D.) of 23.4 ± 4.6 at baseline to 10.7 ± 4.5 at eight weeks. Six out of 13 patients were full responders and four were partial responders. The mean (±S.D.) effective dose of dipyridamole at eight weeks was 281.8 ± 57.5 mg/day. Sleep variables also improved, and the mean (±S.D.) periodic leg movement index decreased from 26.7 ± 7.2 to 4.3 ± 1.9. Dipyridamole was generally well tolerated. Main side effects were abdominal cramps, diarrhea, dizziness, and flushing. ConclusionsThese preliminary results suggest that dipyridamole has significant therapeutic effects on both sensory and motor symptoms, as well as sleep. In addition, it provides evidence that hypoadenosinergic mechanisms play a central role in RLS. Classification of evidenceThe study provides class III evidence supporting the therapeutic effects of dipyridamole in RLS.

Nerve Decompression and Restless Legs Syndrome: A Retrospective Analysis.

Restless legs syndrome (RLS) is a prevalent sleep disorder affecting quality of life and is often comorbid with other neurological diseases, including peripheral neuropathy. The mechanisms related to RLS symptoms remain unclear, and treatment options are often aimed at symptom relief rather than etiology. RLS may present in distinct phenotypes often described as "primary" vs. "secondary" RLS. Secondary RLS is often associated with peripheral neuropathy. Nerve decompression surgery of the common and superficial fibular nerves is used to treat peripheral neuropathy. Anecdotally, surgeons sometimes report improved RLS symptoms following nerve decompression for peripheral neuropathy. The purpose of this retrospective analysis was to quantify the change in symptoms commonly associated with RLS using visual analog scales (VAS). Forty-two patients completed VAS scales (0-10) for pain, burning, numbness, tingling, weakness, balance, tightness, aching, pulling, cramping, twitchy/jumpy, uneasy, creepy/crawly, and throbbing, both before and 15 weeks after surgical decompression. Subjects reported significant improvement among all VAS categories, except for "pulling" (P = 0.14). The change in VAS following surgery was negatively correlated with the pre-surgery VAS for both the summed VAS (r = -0.58, P < 0.001) and the individual VAS scores (all P < 0.01), such that patients who reported the worst symptoms before surgery exhibited relatively greater reductions in symptoms after surgery. This is the first study to suggest improvement in RLS symptoms following surgical decompression of the common and superficial fibular nerves. Further investigation is needed to quantify improvement using RLS-specific metrics and sleep quality assessments.

Intravenous iron administration in restless legs syndrome : An observational study in geriatric patients.

This observational study was carried out to investigate the effect of intravenous (i.v.) iron administration on the clinical symptoms of restless legs syndrome (RLS) in geriatric outpatients over 65 years old. In this study geriatric outpatients (mean 4.5 ± 3.4 comorbidities and 5.7 ± 4.4 drugs taken) were recruited according to the following inclusion criteria: ≥ 65 years, diagnosis of RLS due to iron deficiency, i.e. ferritin < 50µg/l or transferrin saturation (TFS) < 16 %) as well as no other iron therapy within 2 weeks prior to the study. Of the patients 7 (41 %) received 500mg ferric carboxymaltose (FCM) and 10 patients (59 %) received iron gluconate (62.5mg) based on the degree of iron deficiency. As assessed by the international RLS severity scale (IRLS) symptoms were recorded 3 times: at the beginning of iron therapy (t0), after 2 weeks (t1) and after 12 weeks (t2). A total of 17 patients (13 female, 4 male, mean age 73.2 ± 5.9 years) were included. The IRLS score significantly improved in all patients as shown by an average decrease from 30.2 (± 4.3) to 20.2 (± 4.7) (p < 0.001) after 2 weeks of i.v. iron treatment and to 23.2 ± 6.6 (p < 0.001) after 12 weeks. There was a high correlation between ferritin values and the IRLS score (C 0.729, p < 0.001). The part of the IRLS referring to activities of daily living (ADL) improved from a median of 3 (scores 3-4) to 2 (scores 2-3, p = 0.001) after 2 weeks (effect size - 0.6). In this study group of geriatric outpatients i.v. administration of iron was associated with a significant improvement of symptoms in RLS as assessed by the IRLS score 2 weeks after treatment. In geriatric patients with RLS associated with iron deficiency, i.v. iron administration should be considered regarding improvement of RLS symptoms and ADL.

Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome.

An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted.

Microsubthalamotomy improves sleep in patients affected by advanced Parkinson’s disease

BackgroundDeep brain stimulation of the subthalamic nucleus (STN-DBS) improves sleep in patients affected by Parkinson’s disease (PD). Since microsubthalamotomy (mSTN) shows positive effects on motor symptoms, it could improve sleep in PD patients. Our goals were: to assess the effects of mSTN on sleep in patients affected by advanced PD; and to look for a correlation between sleep and motor features after the neurosurgical procedure. MethodsFifteen patients who underwent bilateral STN-DBS were enrolled. Subjective sleep evaluation was assessed using the Parkinson’s Disease Sleep Scale (PDSS). Data on sleep schedule and presence of restless legs syndrome (RLS) were obtained. Objective sleep features were investigated by polysomnography (PSG). To evaluate the mSTN effect, we compared motor state and sleep features before and after the neurosurgical procedure, before the programmable pulse generator was switched on. ResultsmSTN had beneficial effects on motor state and sleep features. After the surgery, the mean total PDSS score increased from 84.0±25.2 to 115.2±16.6 (P<0.001). PD patients reported longer total sleep time duration, decreased daytime sleepiness, and improvement in RLS symptoms. PSG data showed an increase in total sleep time and sleep efficiency with a decrease in wakefulness after sleep onset and arousal index. No correlation between motor improvements and sleep features modifications was observed after mSTN. ConclusionsmSTN improves sleep quality and ameliorates several sleep complaints, as well as motor symptoms, in advanced PD patients who have undergone STN-DBS.

Ascertainment of iron deficiency and depletion in blood donors through screening questions for pica and restless legs syndrome

Pica and restless legs syndrome (RLS) are associated with iron depletion and deficiency. The presence of pica and RLS was prospectively assessed in blood donors. During a 39-month period, 1236 donors deferred for fingerstick hemoglobin (Hb) level of less than 12.5 g/dL and 400 nondeferred "control" donors underwent health screening and laboratory testing (complete blood count, ferritin, iron, transferrin). Pica and RLS were assessed by direct questioning. Deferred donors and iron-deficient control donors were given 325 mg of ferrous sulfate daily for 60 days. Reassessments were performed and additional iron tablets dispensed at subsequent visits. Pica was reported in 11% of donors with iron depletion or deficiency, compared with 4% of iron-replete donors (p < 0.0001). Pagophagia (ice pica) was most common and often of extraordinary intensity. Female sex, younger age, and lower mean cell volume and transferrin saturation values were strongly associated with pica. Donors with pica given iron reported a marked reduction in the desire to consume the nonnutritive substance by Days 5 to 8 of therapy, with disappearance of symptoms by Days 10 to 14. RLS was reported in 16% of subjects with iron depletion or deficiency compared with 11% of iron-replete donors (p = 0.012). Iron replacement generally resulted in improvement of RLS symptoms; however, at least 4 to 6 weeks of iron therapy was necessary. The presence of pica is associated with a high probability of iron depletion or deficiency in blood donors; however, RLS lacks a strong correlation in this population. Screening questions for pagophagia may be useful in the ascertainment of iron deficiency in donors and may identify those who would benefit from oral iron.

The Effect of Ropinirole on the Quality of Life in Patients with Restless Legs Syndrome in Korea: An 8-Week, Multicenter, Prospective Study

Background and PurposeDopamine agonists are first-line drugs for treating the symptoms of restless legs syndrome (RLS). However, few studies have investigated the effect of dopamine agonists on the quality of life (QoL) in RLS patients. We conducted a study to determine whether ropinirole exerts positive effects on the QoL in RLS patients and to analyze the underlying factors.MethodsPrimary RLS patients from eight medical centers were recruited in the study. They were evaluated in the baseline phase using various questionnaires including the Korean versions of the International Restless Legs Scale (K-IRLS), RLS QoL questionnaire (K-RLSQoL), and the Short Form 36 Health Survey (SF-36). After taking ropinirole for 8 weeks the same questionnaires were again completed as a re-evaluation. We analyzed the statistical difference using a paired t-test, a Pearson's correlation, and a stepwise multiple regression in order to identify the factors associated with the QoL change.ResultsA total of 107 subjects, including 65 (60.7%) females, completed this study. They were aged 51.68±14.80 years (mean±SD) and had a symptom duration of 8.8±9.0 months. After treatment with ropinirole, there were significant improvements on the K-RLSQoL, SF-36, and K-IRLS. The Pearson's correlation analysis showed that the improvement of QoL in RLS patients was significantly correlated with the severity of RLS (r=0.236, p<0.014) at baseline.ConclusionsThe results from this study suggest that treatment with ropinirole can improve the QoL in RLS patients. The improvement in the QoL is more related with the improvement of RLS symptoms.

Clozapine-Induced Restless Legs Syndrome Treated With Aripiprazole

Clozapine-Induced Restless Legs Syndrome Treated With Aripiprazole

Gabapentin Enacarbil

Oral gabapentin enacarbil is approved in adult patients for the treatment of moderate to severe primary restless legs syndrome (RLS) [featured indication] and the management of postherpetic neuralgia. In the 12-week Patient Improvements in Vital Outcomes following Treatment (PIVOT) RLS I and II trials in adult patients with moderate to severe primary RLS (n > 500 total evaluable), once-daily gabapentin enacarbil 600 or 1,200 mg significantly improved mean International Restless Legs Scale (IRLS) total scores compared with placebo, with significantly higher investigator-rated Clinical Global Impression-Improvement (CGI-I) responder rates in gabapentin enacarbil groups than in placebo groups. Improvements in other sleep outcomes (assessed using various scales) also generally favoured gabapentin enacarbil treatment. These data are supported by results from a polysomnography, crossover (two 4-week treatment periods) trial (n > 100 evaluable). Improvements in RLS symptoms with gabapentin enacarbil were maintained in a 52-week extension study of clinical trials, including PIVOT RLS I and II. The longer-term efficacy of gabapentin enacarbil in patients with moderate to severe RLS was also demonstrated in the 36-week PIVOT RLS Maintenance study and a 52-week noncomparative study conducted in Japan. Gabapentin enacarbil was generally well tolerated in adult patients with RLS participating in short- and longer-term clinical trials. The most common treatment-emergent adverse events were somnolence/sedation and dizziness. Most adverse events were of mild to moderate severity, with relatively few patients discontinuing treatment because of an adverse event.

Ascertainment of Iron Depletion and Deficiency in Blood Donors Through Screening Questions for Pica and Restless Legs Syndrome.

Abstract 2283 Background:Pica and restless legs syndrome (RLS) are associated with iron depletion and deficiency. Pica refers to the compulsive craving for and persistent consumption of non-nutritive substances. Pagophagia, the pathological consumption of ice, is a specific pica strongly associated with iron deficiency. RLS is a neurological movement disorder characterized by uncomfortable sensations in the lower extremities, with a compelling urge to move the extremities to relieve the discomfort. Primary RLS is a central nervous system disorder; however, secondary RLS may be caused or exacerbated by iron deficiency. The purpose of this study was to prospectively assess the prevalence of pica and RLS in blood donors presenting to a hospital-based donor center, to correlate the findings with donor hemoglobin and iron levels, and to study the effects of oral iron replacement on the resolution of symptoms. Methods:During a 39-month period, 1236 blood donors deferred for fingerstick hemoglobin <12.5 g/dL and 400 non-deferred “control” donors underwent health screening and laboratory testing (CBC, ferritin, iron, transferrin). Iron deficiency was defined as a ferritin level below the institutional reference range of 9 mcg/L in females and 18 mcg/L in males. Iron depletion was defined as a ferritin of 9 – 19 mcg/L in females and 18 – 29 mcg/L in males. Pica and RLS were assessed by direct questioning. Deferred donors and iron-deficient control donors were given ferrous sulfate 325 mg daily for 60 days. Reassessments were performed and additional iron tablets dispensed at subsequent visits. Results:Pica was reported in 11% of donors with iron depletion/deficiency, compared with 4% of iron-replete donors (p<0.0001). The prevalence of pica rose to 21% in females with ferritin <9 mcg/L. Pagophagia (ice pica) was most common and was often of extraordinary intensity, with characteristics of an addiction. Donors with pagophagia given iron reported a marked reduction in the desire to eat ice by day 5–8 of therapy, with disappearance of symptoms by day 10–14. RLS was reported in 16% of subjects with iron depletion/deficiency compared with 11% of iron-replete donors (p=0.012). Iron replacement generally resulted in improvement of RLS symptoms, however, at least 4–6 weeks of iron therapy was necessary. The positive predictive values of pica and RLS in iron deficient/depleted blood donors were 73% and 58%, respectively. Conclusion:The presence of pica is highly predictive of iron depletion/deficiency in blood donors; however, RLS lacks a strong correlation in this population. Screening questions for pica, in particular pagophagia, may be useful in the ascertainment of iron depletion and deficiency in blood donors and may identify those who would benefit from oral iron therapy. Disclosures:No relevant conflicts of interest to declare.

Linking restless legs syndrome with Parkinson's disease: clinical, imaging and genetic evidence

Restless legs syndrome (RLS) and Parkinson's disease (PD) are both common neurological disorders. There has been much debate over whether an etiological link between these two diseases exists and whether they share a common pathophysiology. Evidence pointing towards a link includes response to dopaminergic agents in PD and RLS, suggestive of underlying dopamine dysfunction in both conditions. The extrastriatal dopaminergic system, in particular altered spinal dopaminergic modulation, may be variably involved in PD patients with RLS symptoms. In addition, there is now evidence that the nigrostriatal system, primarily involved in PD, is also affected in RLS. Furthermore, an association of RLS with the parkin mutation has been suggested. The prevalence of RLS has also been reported to be increased in other disorders of dopamine regulation. However, clinical association studies and functional imaging have produced mixed findings. Conflicting accounts of emergence of RLS and improvement in RLS symptoms after deep brain stimulation (DBS) also contribute to the uncertainty surrounding the issue. Among the strongest arguments against a common pathophysiology is the role of iron in RLS and PD. While elevated iron levels in the substantia nigra contribute to oxidative stress in PD, RLS is a disorder of relative iron deficiency, with symptoms responding to replacement therapy. Recent ultrasonography studies have suggested that, despite overlapping clinical features, the mechanisms underlying idiopathic RLS and RLS associated with PD may differ. In this review, we provide a concise summary of the clinical, imaging and genetic evidence exploring the link between RLS and PD.

Review of the Treatment of Restless Legs Syndrome: Focus on Gabapentin Enacarbil

The FDA approved gabapentin enacarbil in 2011 as the first non-dopaminergic agent for the treatment of restless legs syndrome (RLS) symptoms. Although gabapentin enacarbil is a pro-drug of gabapentin, its pharmacokinetics differ. Absorption of gabapentin enacarbil is more predictable, and inter-patient variability in bioavailability is lower than that of gabapentin. Studies have demonstrated superiority of gabapentin enacarbil compared to placebo. Comparisons to currently available RLS treatments are lacking, but clinical trials demonstrate comparable improvement in RLS symptoms to the dopamine agonists ropinirole and pramipexole, which are usually considered first-line therapy for daily RLS symptoms. Gabapentin enacarbil was well tolerated in clinical trials. The role of the drug in RLS treatment remains undefined, although it will likely be used as an alternative for refractory RLS when other treatments have failed. Additionally, gabapentin enacarbil may be recommended for patients with daily RLS symptoms that are less intense or are associated with pain as an alternative to dopamine agonists.

Poor effect of guideline based treatment of restless legs syndrome in clinical practice

BackgroundNumerous randomised controlled trials have proved the efficacy of dopaminergic and non-dopaminergic drugs in the treatment of restless legs syndrome (RLS). In contrast, epidemiological data demonstrate generally insufficient RLS treatment...

Long-term Maintenance Treatment of Restless Legs Syndrome With Gabapentin Enacarbil: A Randomized Controlled Study

To assess maintenance of efficacy and tolerability of gabapentin enacarbil in patients with moderate to severe primary restless legs syndrome (RLS). This study (conducted April 18, 2006, to November 14, 2007) comprised a 24-week, single-blind (SB) treatment phase (gabapentin enacarbil, 1200 mg) followed by a 12-week randomized, double-blind (DB) phase. Responders from the SB phase (patients with improvements on the International Restless Legs Scale [IRLS] and investigator-rated Clinical Global Impression-Improvement scale at week 24 and stable while taking a gabapentin enacarbil dose of 1200 mg for at least 1 month before randomization) were randomized to gabapentin enacarbil, 1200 mg, or placebo once daily at 5 pm with food. The primary end point was the proportion of patients experiencing relapse (worse scores on the IRLS and investigator-rated Clinical Global Impression of Change scale on 2 consecutive visits at least 1 week apart or withdrawal because of lack of efficacy) during the DB phase. A total of 221 of 327 patients completed the SB phase, 194 (96 in the gabapentin enacarbil group and 98 in the placebo group) were randomized to DB treatment, and 168 (84 in the gabapentin enacarbil group and 84 in the placebo group) completed the DB phase. A significantly smaller proportion of patients treated with gabapentin enacarbil (9/96 [9%]) experienced relapse compared with the placebo-treated patients (22/97 [23%]) (odds ratio, 0.353; 95% confidence interval, 0.2-0.8; P=.02). Somnolence and dizziness were the most common adverse events. One death occurred (unintentional choking during the SB phase) and was judged as being unrelated to the study drug. No clinically relevant changes were observed in laboratory values, in vital signs, or on electrocardiograms. Gabapentin enacarbil, 1200 mg, maintained improvements in RLS symptoms compared with placebo and showed long-term tolerability in adults with moderate to severe primary RLS for up to 9 months of treatment.

Depressive Disorders in Restless Legs Syndrome

Epidemiological studies report a 2- to 4-fold risk of a depressive disorder in patients with restless legs syndrome (RLS) compared with healthy controls. The high prevalence rates of depression in RLS indicate an association between the two disorders. Severe sleep disturbance due to the nightly occurrence of RLS symptoms is a common complaint of patients with moderate or severe RLS and may substantially contribute to the emergence of depressive symptoms. Difficulty in the diagnosis of a depressive disorder in patients with RLS may arise from the overlap of symptoms in the two disorders, as sleep-related complaints are frequent both in RLS and depression. The treatment of depression in RLS has some unique aspects, as several antidepressants have been reported to trigger or worsen RLS. To date, no studies have been published regarding the course of depression in untreated and treated patients with RLS. On the other hand, the presence of co-morbid depression can have a substantial impact on the global treatment outcome. In patients with co-morbid moderate/severe depression, antidepressant therapy in parallel with or shortly after commencing RLS treatment is usually necessary. Data from recent trials with dopamine receptor agonists indicate that mild to moderate depressive symptoms are often relieved with improvement of RLS symptoms.

Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: A randomized, double-blind, placebo-controlled study

Background and Purpose Restless Legs Syndrome (RLS) is a primary disorder of sensation that affects sleep and has been associated with iron deficiency. The purpose of this study was to determine if symptomatic RLS patients with low-normal serum ferritin levels benefit from oral iron replacement. Patients and Methods This was a randomized, placebo-controlled, double-blinded study. Eligible patients were randomized to oral iron therapy vs. appearance-matched placebo and followed over a 12 week period. Results Baseline International Restless Leg Scale (IRLS) scores for the treatment (24.8 ± 5.72) and placebo (23.0 ± 5.03) groups were similar. Baseline ferritin levels for the treatment (40.6 ± 15.3 ng/ml) and placebo (36.7 ± 20.8 ng/ml) groups were also similar. After 12 weeks, IRLS scores decreased more in the treatment arm (10.3 ± 7.40) than in the placebo arm (1.14 ± 5.64), ( p = 0.01). Ferritin levels increased more in the treatment arm (25.1 ± 20.3 ng/ml) than in the placebo arm (7.5 ± 13.7 ng/ml), ( p = 0.04). We observed a nonsignificant trend toward improved quality of life in the treated patients, ( p = 0.07). Conclusions This is the first double-blinded, placebo-controlled study to demonstrate statistically significant improvement in RLS symptoms using oral iron therapy in patients with low-normal ferritin. The findings from this study suggest that additional larger randomized placebo-controlled trials of iron as treatment for patients with low-normal ferritin are warranted.

Ropinirole treatment for restless legs syndrome

Restless legs syndrome (RLS) is a chronic neurological disorder associated with sleep disturbance. Ropinirole, a non-ergot dopamine agonist, has been widely studied for the treatment of moderate-to-severe primary RLS in a comprehensive clinical development program. In these studies, ropinirole was effective in significantly improving the symptoms of RLS, compared with placebo, in patients with moderate-to-severe primary RLS. These improvements are supported by data from individual studies, as well as by pooled analyses. Significant improvements in RLS symptoms were observed within 2 nights of treatment. Ropinirole also produced significant benefits on objective measures of RLS motor symptoms, such as periodic leg movements; and on subjective measures of sleep, ropinirole was generally well tolerated. A newly developed extended-release formulation of ropinirole may benefit patients who warrant an extended duration of therapy.

Ropinirole treatment for restless legs syndrome

Background: Restless legs syndrome (RLS) is a chronic neurological disorder associated with sleep disturbance. Objective: Prepare a drug evaluation of the non-ergot dopamine agonist ropinirole in RLS. Methods: Review of scientific literature on RLS, particularly focusing on treatment with ropinirole. Conclusion: Ropinirole has been studied for treatment of moderate to severe primary RLS in a comprehensive clinical development program. Ropinirole significantly improved symptoms of RLS, versus placebo, in patients with primary RLS. These improvements are supported by data from individual studies and pooled analyses. Significant improvements in RLS symptoms were observed within two nights of treatment. Ropinirole also produced significant benefits on objective measures of RLS motor symptoms, such as periodic leg movements, and subjective measures of sleep. Ropinirole was generally well tolerated.

Rotigotine Transdermal Patch

Rotigotine is a non-ergolinic dopamine receptor agonist, formulated as a silicone-based transdermal patch, which has been evaluated for use in the treatment of adults with moderate to severe restless legs syndrome (RLS). Transdermal rotigotine improved the symptoms of RLS in two well designed 6-month trials in adults with idiopathic, moderate to severe RLS. Rotigotine (1-3 mg/24 h in one study and 2 or 3 mg/24 h in the other) decreased the International RLS Study Group Severity Rating Scale (IRLS) sum score and the Clinical Global Impression (CGI) item-1 assessment (severity of symptoms) from baseline (co-primary endpoints) to a significantly greater extent than placebo. Over half of rotigotine recipients were classified as treatment responders according to the IRLS sum score and CGI item-1 and item-2 ratings. Improvements in RLS symptoms have been maintained in the long term with rotigotine, according to the 3-year results of an open-label extension trial. Transdermal rotigotine was generally well tolerated in clinical trials and long-term extension studies in patients with moderate to severe RLS. There was a low risk of augmentation (i.e. intensification of RLS symptoms) with rotigotine, although further evaluations are required to ascertain if continuous dopaminergic stimulation has the effect of limiting or preventing augmentation.