Treatment Of Restless Legs Syndrome Research Articles

Algorithms for the diagnosis and treatment of restless legs syndrome in primary care.

BackgroundRestless legs syndrome (RLS) is a neurological disorder with a lifetime prevalence of 3-10%. in European studies. However, the diagnosis of RLS in primary care remains low and mistreatment is common.MethodsThe current article reports on the considerations of RLS diagnosis and management that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored task force consisting of experts and primary care practioners. The task force sought to develop a better understanding of barriers to diagnosis in primary care practice and overcome these barriers with diagnostic and treatment algorithms.ResultsThe barriers to diagnosis identified by the task force include the presentation of symptoms, the language used to describe them, the actual term "restless legs syndrome" and difficulties in the differential diagnosis of RLS.ConclusionThe EURLSSG task force reached a consensus and agreed on the diagnostic and treatment algorithms published here.

Efficacy and augmentation during 6 months of double-blind pramipexole for restless legs syndrome

Background Pramipexole is an effective treatment for restless legs syndrome (RLS), but no controlled studies have lasted >12 weeks. Methods RLS patients ( N = 331) with pretreatment serum ferritin >30 ng/mL were randomly assigned to take double-blind optimized pramipexole (0.125–0.75 mg/d) or placebo for 26 weeks. The primary efficacy endpoint was change in International RLS Study Group Rating Scale (IRLS) score. Other endpoints assessed global change, symptoms, and QoL. Patients maintained symptom diaries. Cases meeting predefined criteria for suspected augmentation were reviewed by a blinded expert panel, which used a predefined algorithm. Results Among 321 patients providing post-baseline data, of whom 234 completed 26 weeks, pramipexole was more effective than placebo by multiple endpoints, including an adjusted mean IRLS score change of −13.7 vs. −11.1 ( p = 0.0077) and an IRLS responder rate (⩾50% score reduction) of 58.6% vs. 42.8% ( p = 0.0044). Efficacy showed considerable country-to-country variability. Six-month incidence of confirmed augmentation was 9.2% for pramipexole and 6.0% for placebo. The rate increased with treatment duration for pramipexole but not placebo. Treatment-related adverse events (AEs) were more likely for pramipexole than for placebo, but discontinuation due to AEs was less likely. Conclusions During a 6-month period, pramipexole was effective, safe, and generally well tolerated. Because risk of augmentation may have increased over 6 months, it should be studied in longer trials. Beginning or mild augmentation is difficult to distinguish from natural RLS fluctuation, at least in a non-iron-deficient population.

Diagnosis and treatment of restless legs syndrome should be concerned

Diagnosis and treatment of restless legs syndrome should be concerned

Levodopa for the treatment of restless legs syndrome

Background Levodopa plus dopamine decarboxylase inhibitor is a common treatment for restless legs syndrome (RLS). Objectives To evaluate efficacy and safety of levodopa for RLS compared to placebo and other active agents. Search methods We searched CENTRAL (The Cochrane Library 2008, Issue 4), MEDLINE, EMBASE, PsycINFO and CINAHL, from January 1985 to December 2008, reference lists of articles, and contacted pharmaceutical companies. Selection criteria We included double‐blind randomised controlled trials (RCT) investigating levodopa treatment versus placebo or other treatment for at least seven days in patients with RLS (age ≥ 18 years). Outcomes included symptom severity, CGI‐I, objective as well as self rated sleep parameters, quality of life, and safety parameters. Data collection and analysis Two authors extracted data, assessed risk of bias, and contacted pharmaceutical companies and authors for additional information. We collected dropouts due to adverse events and patients experiencing adverse events. Main results Six placebo controlled and three active controlled RCTs were included (521 participants). Symptom severity (11 point rating scale, 0 points indicating no symptoms, 10 points indicating maximally severe symptoms) was more reduced with levodopa than placebo in two studies (mean difference (MD) ‐1.34, 95% confidence interval (CI) ‐2.18 to ‐0.5, P = 0.002). Periodic limb movements in sleep per hour of sleep (PLMS‐Index; PLMSI) improved by ‐26.28/h compared to placebo (95% CI ‐30.53 to ‐22.02, P < 0.00001).The CGI‐I changed more with levodopa than placebo in two studies (MD ‐1.25, 95% CI ‐1.89 to ‐0.62, P = 0.0001). In two studies, sleep quality (sleep questionnaire, visual analogue scale) showed a large effect (standardised mean difference (SMD) 0.92, 95% CI 0.52 to 1.33, P < 0.00001) whereas quality of life (50 mm Visual Analogue Scales) improved by 3.23 compared to placebo (95% CI 1.64 to 4.82, P < 0.0001). Few patients dropped out of treatment (3 of 218 patients) but more levodopa treated patients experienced adverse events than with placebo (odds ratio 2.61, 95% CI 1.35 to 5.04, P = 0.004). Two dopamine agonist controlled studies showed smaller effects with levodopa than cabergoline and pramipexole on the IRLS (MD 5.25, 95% CI 2.10 to 8.40, P =0.001), CGI‐I (MD 0.62, 95% CI 0.37 to 0.87, P < 0.00001), and quality of life (MD 5.54, 95% CI 2.65 to 8.43, P = 0.0002). Authors' conclusions Levodopa is efficacious for the short‐term treatment of RLS. Augmentation, the clinically most relevant adverse event, was not investigated sufficiently.

Treatment of restless legs syndrome with pregabalin: A double-blind, placebo-controlled study

Treatment of restless legs syndrome with pregabalin: A double-blind, placebo-controlled study

Oxidative stress and autonomic nervous system functions in restless legs syndrome

Oxidative stress has been implicated in over 100 disorders in recent years; however, the situation in restless legs syndrome (RLS) has not been studied yet. Fifty patients with RLS not medicated for RLS and 50 sex- and age-matched, healthy controls and controls with no pathology except mild iron deficiency or iron deficiency anaemia were enrolled. Patients with secondary RLS other than iron deficiency were excluded. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), arylesterase (ARE), paraoxonase (PON), stimulated paraoxonase (stim-PON), lipid hydroperoxides (LOOHs), acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE) were measured. Heart rate variability (HRV) analysis was performed. TOS, ARE and AChE were increased (P = 0·018, P < 0·001 and P < 0·001, respectively), whereas LOOHs were decreased (P < 0·001) in RLS group. TAS, OSI, PON and stim-PON were comparable. Erythrocyte sedimentation rate (ESR) and mean platelet volume (MPV) were increased (P = 0·021 and P = 0·037, respectively) in RLS group. HRV triangular index (HRVi) was lower (P = 0·012) in RLS group. Other HRV parameters were similar. Increased AChE and decreased LOOHs, which were influenced by increased PON1, were considered as indicators of efforts towards the protection of dopaminergic activity in central nervous system in RLS group. Increased ESR, MPV and low HRVi indicate elevated sympathetic activity in RLS group. Elevated sympathetic activity might be beneficial in relieving RLS symptoms, also causing increases in TOS. The evidence we found regarding oxidative stress and autonomic nervous system might be seminal in RLS treatment.

A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome

Background Restless legs syndrome (RLS) is a chronic disease, which is managed with palliative medications that are likely to be required for a patient’s lifetime. It is, therefore, important to know the long-term consequences of these treatments. Currently, the most commonly prescribed treatment for RLS is one of the dopamine (DA) agonists. Most of what we understand about efficacy and side effects of the DA agonists are, however, derived from relatively short-term studies. This is particularly a problem since these medications produce in some patients a significant increase or augmentation of RLS symptoms known to occur during the first 2 years of treatment and perhaps even later in treatment. The primary aim of this study was to determine the long-term efficacy (10-year) for commonly used RLS medication types: dopaminergic agonists and opioids. Methods Records of all RLS patients treated in one tertiary care center with pramipexole, pergolide or methadone during the years 1997–2007 were reviewed. The duration and reason for any discontinuation of treatment and medication doses were recorded. Results Annual rates for discontinuing treatment persisted for up to 10 years of treatment and were fairly constant after the first year at 9% for pramipexole, 8% for pergolide, and 0% for methadone. Similarly, annual augmentation rates were fairly constant after the first year and persisted for up to 10 years at 7% for pramipexole, 5% for pergolide, and 0% for methadone. The percentage continuing on the treatment medication for over 5 years was 58% for pramipexole and 35% for pergolide. Conclusions The DA agonists appear to have a limited period of clinical utility for many patients. Severe augmentation, while not common in any 1 year, can develop even after years on the medication. Methadone, in contrast, shows neither augmentation nor major problems with continued efficacy after the first year of treatment.

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

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

Psychological distress of patients suffering from restless legs syndrome: a cross-sectional study

BackgroundRestless legs syndrome (RLS) is a chronic disorder with substantial impact on quality of life similar to that seen in diabetes mellitus or osteoarthritis. Little is known about the psychological characteristics of RLS patients although psychological factors may contribute to unfavourable treatment outcome.MethodsIn an observational cross-sectional design, we evaluated the psychological features of 166 consecutive RLS patients from three outpatient clinics, by means of the Symptom Checklist 90-R (SCL-90-R) questionnaire. Additionally, the Beck Depression Inventory-II (BDI-II) and the International RLS Severity Scale (IRLS) were measured. Both treated and untreated patients were included, all patients sought treatment.ResultsUntreated patients (n = 69) had elevated but normal scores on the SCL-90-R Global Severity Index (GSI; p = 0.002) and on the sub-scales somatisation (p < 0.001), compulsivity (p = 0.003), depression (p = 0.02), and anxiety (p = 0.004) compared with a German representative sample. In the treated group, particularly in those patients who were dissatisfied with their actual treatment (n = 62), psychological distress was higher than in the untreated group with elevated scores for the GSI (p = 0.03) and the sub-scales compulsivity (p = 0.006), depression (p = 0.012), anxiety (p = 0.031), hostility (p = 0.013), phobic anxiety (p = 0.024), and paranoid ideation (p = 0.012). Augmentation, the most serious side effect of dopaminergic, i.e. first-line treatment of RLS, and loss of efficacy were accompanied with the highest psychological distress, as seen particularly in the normative values of the sub-scales compulsivity and anxiety. Generally, higher RLS severity was correlated with higher psychological impairment (p < 0.001).ConclusionSeverely affected RLS patients show psychological impairment in multiple psychological domains which has to be taken into account in the treatment regimen.

Liver toxicity possibly related with ropinirole use in the treatment of restless legs syndrome

Liver toxicity possibly related with ropinirole use in the treatment of restless legs syndrome

The Relationship With Iron and Health Outcomes in Persons With Restless Legs Syndrome

Restless Legs Syndrome (RLS) is a sleep disorder cause by inadequate iron metabolism. However, no studies have identified the impact of iron in RLS patients on sleep, depression, fatigue, or quality of life (QoL). The aims of this secondary data analysis was to determine relationships (a) between serum iron with RLS symptom severity, sleep quality, daytime sleepiness, depression, fatigue, and quality of life (QoL); and (b) based on demographics, specifically age and ethnicity. Data were collected on iron and ferritin concentrations in 48 persons with RLS. Low serum iron levels were measured in 32% of the participants with only 1 person (4%) treated with iron supplementation. General linear models identified age and race as covariants: (a) being White (p = .047) and higher iron levels (p = .019) were independent predictors of higher social functioning; (b) being White (p = .047) and higher iron levels (p = .004) were independent predictors of less sleepiness; (c) younger age (p = .001) and lower iron levels (p = .025) were independent predictors of depression; and (d) younger age (p = .006) and lower iron levels (p = .005) were independent predictors of fatigue. Findings from this study show that iron supplementation for persons with RLS not only improves motor and sensory symptoms but might also improve sleep, sleepiness, depression, fatigue, and QoL and should be considered by health care providers for treatment of RLS.

Randomized trial of pramipexole for patients with restless legs syndrome (RLS) and RLS-related impairment of mood

ObjectivesPatients with restless legs syndrome (RLS) have an elevated prevalence of mood disorders compared with the general population. We investigated the change of RLS-related mood impairment during treatment of RLS with pramipexole, a dopamine D3/D2 agonist. MethodsAdults with moderate to very severe RLS were enrolled in a 12-week, double-blind, placebo-controlled Phase IV pramipexole trial. A moderate to very severe RLS-related mood disturbance at baseline (score⩾2 on Item 10 of the International RLS Study Group Rating Scale [IRLS]) was also required. Pramipexole (0.125 to 0.75mg once daily) was flexibly titrated over the first 4weeks. ResultsThe intent-to-treat population comprised 199 patients on placebo and 203 on pramipexole. At week 12, adjusted mean total-score changes on IRLS were –14.2±0.7 for pramipexole and –8.1±0.7 for placebo (p<0.0001), and on the Beck Depression Inventory version II, –7.3±0.4 for pramipexole and –5.8±0.5 for placebo (p=0.0199). For IRLS item 10, the 12-week responder rate (reduction to no or mild mood disturbance) was 75.9% for pramipexole and 57.3% for placebo (p<0.0001). Study withdrawal rates were higher for placebo (20.5%) than for pramipexole (12.8%). ConclusionsIn patients with RLS-related mood disturbance, pramipexole improved RLS while also improving RLS-related mood impairment. Tolerability of pramipexole was similar to that in previous studies.

High Prevalence of Restless Legs Syndrome among Patients with Fibromyalgia: A Controlled Cross-Sectional Study

To investigate the prevalence of restless legs syndrome (RLS) in fibromyalgia (FM) and determine the presence and amount of sleep disruption in FM patients with RLS. RLS and FM have been associated in uncontrolled studies using a variety of RLS definitions. We explored this relationship using a cross-sectional study design. FM cases that met the American College of Rheumatology diagnostic criteria were recruited through an academic referral clinic and advertising. Pain- and fatigue-free controls were recruited from the Seattle metropolitan area. We enrolled 172 FM patients (mean age 50 years, 93% female) and 63 pain- and fatigue-free controls (mean age 41 years, 56% female). RLS was ascertained by a self-administered validated diagnostic interview. The age- and gender-adjusted prevalence of RLS was higher in the FM group than the control group (33.0%; 95% CI: 25.9, 40.1 vs. 3.1%; 95% CI: 0.0, 7.4; p = 0.001). Likewise, the FM group was more likely to report RLS (OR = 11.7; 95% CI: 2.6, 53.0), even after adjusting for age and gender. The mean Pittsburgh Sleep Quality Index score was higher among FM patients with RLS than those without (11.8 vs. 9.9; p = 0.01) but subjective limb pain measures did not differ between these 2 groups. There is a higher prevalence and odds of RLS in those with FM compared to controls. Clinicians should routinely query FM patients regarding RLS symptoms because treatment of RLS can potentially improve sleep and quality of life in these patients.

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...

Effects of acute dopamine-agonist treatment in restless legs syndrome on heart rate variability during sleep

ObjectiveTo compare heart rate variability (HRV) changes in patients with restless legs syndrome (RLS) and in healthy subjects, and to evaluate HRV before and after treatment with pramipexole in RLS patients. MethodsA prospective, polysomnographic, single-blind, placebo-controlled study was performed in 23 patients with RLS and 10 healthy subjects. Basal spectral analysis of HRV and phasic heart rate (HR) changes during PLMS were compared between the two groups and, within the RLS group, before and after treatment with placebo or pramipexole. ResultsNo differences were found in the basal sympathovagal balance outside of PLMS between RLS and controls and, in the RLS group, before and after treatment. The amplitude of PLMS-related HR changes was higher in patients than in controls. Treatment with pramipexole decreased the number of PLMS and normalized the increased PLMS-related HR response in RLS subjects. ConclusionsThe repetitive abnormal autonomic response to PLMS might play a role in the increased cardiovascular risk proposed for RLS patients. Pramipexole reduced the number of PLMS and the amplitude of the autonomic response to residual PLMS, without effects on the tonic sympathovagal regulation. D3 receptors in the sympathetic pre-ganglionic neurons of the spinal intermediolateral columns might be a target of pramipexole. The normalization of the HR response could be relevant in reducing the risk of cardiovascular diseases and associated autonomic dysfunctions in patients with RLS.

Treatment of restless legs syndrome during pregnancy

Treatment of restless legs syndrome during pregnancy

Use of near-infrared light to reduce symptoms associated with restless legs syndrome in a woman: a case report

IntroductionWe describe a potential new treatment option for patients suffering from restless legs syndrome. Contemporary treatment for restless legs syndrome consists mostly of dopaminergic drugs that leave some patients feeling nauseated and dizzy. A non-invasive, drug-free option would open new doors for patients suffering from restless legs syndrome.Case presentationA 69-year-old Caucasian woman met International Restless Legs Syndrome Study Group criteria for the diagnosis of restless legs syndrome. She had been afflicted with restless legs syndrome for over 30 years and tried many of the available pharmaceutical remedies without success. For this study she received 30-minute treatment sessions with near-infrared light, three times a week for four weeks. The restless legs syndrome rating scale was used to track symptom changes; at baseline she scored "27" on the 0 to 40 point scale, which is considered to be "severe". Our patient was almost symptom free at week two, indicated by a score of "2" on the rating scale. By week four she was completely symptom free. The symptoms slowly returned during week three post treatment.ConclusionsThe findings suggest that near-infrared light may be a feasible method for treating patients suffering from restless legs syndrome. Undesirable side-effects from medication are non-existent. This study might revive the neglected vascular mechanism theory behind restless legs syndrome and encourage further research into this area.

The pharmacological treatment for uremic restless legs syndrome: Evidence‐based review

Restless legs syndrome (RLS) is a common and often misdiagnosed entity among the general population and it may be more common among dialysis patients, with an estimated prevalence of 6.6 to 21.5%. The treatment for uremic RLS has been controversial and therefore a systematic synthesis of the evidence is needed in order to evaluate the effectiveness and safety of treatments for uremic RLS. This was a systematic review of randomized or quasi-randomized double-blind trials on treatments for uremic RLS. The outcomes considered were relief of RLS symptoms marked on a validated scale, subjective sleep quality, sleep quality measured using night polysomnography and actigraphy, quality of life measured subjectively, and adverse events associated with these treatments. Six eligible clinical trials were included. The results from subjective analyses in these studies were divergent, although objective analyses in one trial showed that there was a statistically significant improvement in periodic leg movement while asleep in the treatment group. No combined analysis (meta-analysis) was performed. The most common adverse event seen was gastrointestinal symptoms. Only a few therapeutic trials on patients with uremia with RLS have been published, and there is insufficient scientific evidence to favor any specific therapeutic regimen for uremic-associated RLS. Therapy using levodopa, dopaminergic agonists, anticonvulsants, and clonidine tend to be effective, but further studies are needed.

The use of gabapentin enacarbil in the treatment of restless legs syndrome

Restless legs syndrome (RLS) is a common sleep-related neurological disorder that is characterized by the urge to move, worsening at rest, improvement with activity, and worsening in the evening and night. Dopamine agonists are usually the first-line therapy. Other agents including benzodiazepines, narcotics, and anticonvulsants have been used to treat RLS. Gabapentin has been shown to improve RLS in a small number of clinical studies, but is limited by its short half-life and variable bioavailability. Gabapentin enacarbil is a novel prodrug of gabapentin designed to overcome these pharmacokinetic limitations. In vitro and in vivo studies have demonstrated that gabapentin enacarbil has improved absorption, bioavailability and pharmacokinetics compared with gabapentin. Phase II and III studies have demonstrated that gabapentin enacarbil is generally well tolerated and is useful in the treatment of RLS.

Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome

Importance to the field: Gabapentin enacarbil (XP13512/GSK1838262) is being explored as an alternative treatment for restless legs syndrome (RLS), which currently relies heavily on dopaminergic agents; however, these latter medications have the reported complications of augmentation. Gabapentin enacarbil shows promising data that it may be equally to more efficacious and have an improved side effect profile than treatment with dopaminergic agents.Areas covered in this review: Gabapentin enacarbil, examined in studies from 2004 to 2009, is a precursor to gabapentin and overcomes gabapentin's unfavorable pharmacokinetic profile and dose-dependent bioavailability. Randomized, controlled studies published in 2009 showed that gabapentin enacarbil outperformed placebo in improving quality and duration of sleep based on subjective report, investigator observation and objective measures in clinical trials. These trials show gabapentin enacarbil is well tolerated and safe, with a side-effect profile similar to gabapentin.What the reader will gain: The reader will gain a thorough understanding of the current treatments available for RLS and how gabapentin enacarbil offers a potential breakthrough in expanding on these treatment options for both improved efficacy and tolerability.Take home message: Based on these findings, gabapentin enacarbil offers a promising alternative treatment for individuals requiring pharmacological intervention for their RLS symptoms.