International Restless Legs Syndrome Research Articles

Clinical efficacy and safety of intravenous ferric carboxymaltose for treatment of restless legs syndrome: a multicenter, randomized, placebo-controlled clinical trial.

Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS. A total of 209 adult patients with a baseline International RLS (IRLS) score ≥ 15 were randomized (1:1) to FCM (750 mg/15 mL) or placebo on study days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose. Co-primary efficacy endpoints were changed from baseline in IRLS total score and the proportion of patients rated as much/very much improved on the Clinical Global Impression (CGI)-investigator (CGI-I) scale at day 42 in the "As-Treated" population. The "As-Treated" population comprised 107 FCM and 101 placebo recipients; 88 (82.2%) and 68 (67.3%), respectively, completed the day 42 assessment. The IRLS score reduction was significantly greater with FCM versus placebo: least-squares mean (95% confidence interval [CI]) -8.0 (-9.5, -6.4) versus -4.8 (-6.4, -3.1); p = .0036. No significant difference was observed in the proportion of FCM (35.5%) and placebo (28.7%) recipients with a CGI-I response (odds ratio 1.37 [95% CI: 0.76, 2.47]; p = .2987). Fewer patients treated with FCM (32.7%) than placebo (59.4%) received RLS interventions between day 5 and study end (p = .0002). FCM was well tolerated. The IRLS score improved with intravenous FCM versus placebo, although the combination of both co-primary endpoints was not met. Potential methodological problems in the study design are discussed.

Sleep disorders among elderly in Saudi Arabia: A cross-sectional study.

Aging has been shown to have an impact on sleep patterns, necessitating a deep dive into understanding the complex relationship between aging and sleep disorders. This study aimed to assess the prevalence of sleep disorders among elderly people and identify the associations between different factors and sleep disorders in this age group. This study was conducted at nursing homes in Jeddah. The target populations were those aged 65 years and older (geriatric group) and those aged younger than 65 years (nongeriatric group). Validated questionnaires, including the Athens Insomnia Scale, Berlin Questionnaire, Epworth Sleepiness Scale, International restless legs syndrome (RLS) Study Group, and Pittsburgh Sleep Quality Index, were used to assess different sleep disorders. A total of 313 participants were recruited in the geriatric (n = 153) and nongeriatric (n = 160) groups. Compared with the nongeriatric group, the geriatric group had greater risks of obstructive sleep apnea (OSA) (70.6%) and RLS (40.5%) (P < 0.001). Both groups had a notable prevalence of poor sleep quality (86.6%). Although insomnia was found to be common, there was no significant difference in the prevalence of insomnia between the two groups. In addition, insomnia (odds ratio [OR] = 3.04, confidence interval [CI]: 1.06-8.86, P = 0.037), OSA (OR = 3.17, CI: 1.06-9.41, P = 0.038), and high body mass index (OR = 1.76, CI: 1.63-2.9, P = 0.003) were significantly associated with poor sleep quality. This study revealed that sleep disorders, particularly OSA and RLS, are common in the elderly population in Saudi Arabia.

COMPARISON OF LACOSAMIDE VERSUS LEVODOPA IN THE TREATMENT OF RESTLESS LEGS SYNDROME IN HEMODIALYSIS PATIENTS

ABSTRACT&#x0D; Objective: To compare Lacosamide and Levodopa for treating restless-legs-syndrome in hemodialysis patients in terms of mean change of International Restless Leg Syndrome (IRLS) score.&#x0D; Methods: It was a Randomize control trail done at Department of Medicine &amp; Nephrology Department of Mayo hospital, Lahore from April 2019 to March 2020. After taking approval from institutional-Review-board (IRB) of the King Edward Medical University (KEMU), sixty patients coming to hemodialysis unit of Mayo Hospital, Lahore and fulfilling the inclusion criteria were enrolled for study. We used lottery method and randomly divided them in to two groups that is Group-A: Lacosamide (50 mg) given at bedtime. (30 cases) and Group-B: Levodopa (110 mg) given daily 2 hours before bedtime (30 cases). Treatment was continued for 4 weeks. We calculated IRLS score at start of study and four week after treatment and any Change from baseline was calculated for every patient. That difference of –IRLS score documented on the attached Performa along with demographic details about patient.&#x0D; Results: This study showed that after 4 weeks of treatment there was not much difference seen in International Restless Leg Syndrome score in each treatment groups. i.e. [Pre-Treatment (Lacosamide: 20.80±4.78 vs. Levodopa: 22.60±4.66), Post Treatment (Lacosamide: 14.20±2.89 vs. Levodopa: 15.73±3.58), Mean change of score (Lacosamide: 7.10±4.99 vs. Levodopa: 6.86±6.63 . p - Value = 0.878)&#x0D; Conclusion: This trial concludes that Levodpoa and Lacosamide were equally good in treating Restless-Legs-Syndrome among patients who are on Hemodialysis.&#x0D; Key words: Restless legs syndrome, Hemodialysis, Lacosamide, Levodopa.

Improvement of restless leg syndrome in maintenance hemodialysis patients with limb ischemic preconditioning: a single-center randomized controlled clinical trial

Objective This study evaluated the efficacy and safety of limb ischemic preconditioning (LIPC) in treating restless leg syndrome (RLS) in maintenance hemodialysis (MHD) patients. Methods A total number of 45 patients participated in the study. They were randomly divided into LIPC group and control group. The LIPC was performed by inflating the limb ischemic preconditioning training device in the patient’s thigh to 200 mmHg to create transient ischemia, whereas control group inflated the device to 20 mmHg. International Restless Legs Syndrome (IRLS), Clinical Global Impression Scale (CGI-S), and Medical Outputs Study Sleep Scale were employed to evaluate LIPC effectiveness. The primary endpoint was the ‘rate of clinical improvement in RLS severity’, defined as the percentage of patients who had an IRLS score decrease of ≥5 points in each group. Results After intervention, the rate of clinical improvement in RLS severity was 56.5% in the LIPC group and 13.6% in the control group (13 (56.5) vs 3 (13.6), p = 0.003). In addition, the LIPC group’s IRLS, CGI-S scores, the sleep disturbance and somnolence scores showed a significant downward trend compared to the control group (−5.5 ± 5.3 vs − 1.0 ± 3.8, p = 0.002; −1.7 ± 1.2 vs − 0.5 ± 1.4, p = 0.003; −15.5 ± 17.8 vs 3.7 ± 12.0, p < 0.001; −9.9 ± 18.8 vs − 2.4 ± 8.6, p = 0.003). During the study, there were no serious adverse event in any of the patients. Conclusions LIPC could be employed to effectively and safely alleviate the RLS symptoms in MHD patients.

Long-term dopamine agonist treatment fails to restore altered central sensory processing in restless legs syndrome: Evidence from current perception threshold measurements

ObjectivesAlthough some studies have examined the impact of short-term dopamine agonist treatment on altered central sensory processing in patients with restless legs syndrome (RLS), there is a scarcity of research investigating the effect of long-term treatment with these drugs. The aim of this study is to investigate the long-term impact of dopamine agonist treatment on altered central sensory processing in RLS patients using current perception threshold (CPT) testing. MethodsWe conducted a study of 24 RLS patients, measuring their CPT values before and after dopamine agonist treatment for at least 2 months. Patients were classified as responders or non-responders based on their decrease in International Restless Legs Syndrome (IRLS) score. Clinical parameters were collected and compared pre- and post-treatment. ResultsThe mean duration of treatment with dopamine agonist was 13.6 ± 11.0 months. Our results showed that dopamine agonist treatment significantly improved clinical parameters, including the IRLS score, Visual Analogue Scale, and RLS Quality of Life questionnaire. However, CPT values did not show significant changes for all stimulus frequencies after treatment. Furthermore, we did not find any difference in CPT values before and after treatment in both responders and non-responders. ConclusionsOur study demonstrated that long-term treatment with dopamine agonists effectively reduces RLS symptoms, but does not reverse the altered central sensory processing observed on CPT testing in RLS patients. These results support the notion that the pathophysiology of RLS is multifactorial and not solely driven by dopaminergic dysfunction.

Patterns of sleep disorders after a new coronavirus infection COVID-19

Background. Sleep disorders have a negative impact on many aspects of life. COVID-19 exacerbates this problem in the context of the post-COVID syndrome where sleep disorder is one of the common complaints.Objective. We aimed to assess the frequency of sleep disorders after COVID-19 and the presence of associations between post-COVID sleep disorders and the severity of COVID-19.Material and methods. A cross-sectional study was carried out in Novosibirsk. It included 115 people aged 26 to 74 years (an average age of 54.22 ± 12.48 years) after recovery from COVID-19, which occurred two to eleven months before. Patients underwent questionnaire survey (Spiegel sleep score questionnaire, HADS Anxiety and Depression Scale, International Restless Legs Syndrome (RLS) Severity Scale), examination by a somnologist, and screening night computer pulse oximetry. If an index of desaturations was more than five per hour, we performed overnight somnography by WAtch PAT 200 or polysomnography. Patients were divided into groups depending on the presence of sleep disorders, COVID-19 severity, and their age. Statistical analysis included a descriptive analysis. Odds ratio was assessed by determining the risk measure for dichotomous variables in the contingency table.Results. RLS was the most common post-COVID sleep disorder (n = 63, 75%). However, primary insomnia was diagnosed only in patients with moderate-to-severe course of COVID-19 (n = 3, 9%). There were 40 patients with post-COVID sleep disorder; they had significantly lower sleep time on workdays (7.00 [6.00; 7.50] vs. 7.50 [6.50; 8.00] hours, p = 0.021) and significantly higher mean HADS depression score (5.00 [3.00; 7.00] vs. 3.00 [1.00; 6.00] points, p = 0.006) compared with the corresponding parameters in patients without deterioration of sleep quality. The chance of reduced sleep quality was 11.6 times higher after moderate-to-severe COVID-19 infection than that after mild infection only in patients aged 26-59 years (95% confidence interval 1.42–94.32, p = 0.007).Conclusion. The chance of worsening sleep quality was significantly higher after a moderate-to-severe COVID-19 infection than after mild infection in 26-59-year-old old patients. At the same time, RLS was the most common post-COVID sleep disorder according to our study. Given the importance of sleep disorders, working-age patients after moderate-to-severe COVID-19 infection require active monitoring by doctors in order to timely correct emerging complaints.

Patterns of sleep disorders after a new coronavirus infection COVID-19

Background. Sleep disorders have a negative impact on many aspects of life. COVID-19 exacerbates this problem in the context of the post-COVID syndrome where sleep disorder is one of the common complaints.Objective. We aimed to assess the frequency of sleep disorders after COVID-19 and the presence of associations between post-COVID sleep disorders and the severity of COVID-19.Material and methods. A cross-sectional study was carried out in Novosibirsk. It included 115 people aged 26 to 74 years (an average age of 54.22 ± 12.48 years) after recovery from COVID-19, which occurred two to eleven months before. Patients underwent questionnaire survey (Spiegel sleep score questionnaire, HADS Anxiety and Depression Scale, International Restless Legs Syndrome (RLS) Severity Scale), examination by a somnologist, and screening night computer pulse oximetry. If an index of desaturations was more than five per hour, we performed overnight somnography by WAtch PAT 200 or polysomnography. Patients were divided into groups depending on the presence of sleep disorders, COVID-19 severity, and their age. Statistical analysis included a descriptive analysis. Odds ratio was assessed by determining the risk measure for dichotomous variables in the contingency table.Results. RLS was the most common post-COVID sleep disorder (n = 63, 75%). However, primary insomnia was diagnosed only in patients with moderate-to-severe course of COVID-19 (n = 3, 9%). There were 40 patients with post-COVID sleep disorder; they had significantly lower sleep time on workdays (7.00 [6.00; 7.50] vs. 7.50 [6.50; 8.00] hours, p = 0.021) and significantly higher mean HADS depression score (5.00 [3.00; 7.00] vs. 3.00 [1.00; 6.00] points, p = 0.006) compared with the corresponding parameters in patients without deterioration of sleep quality. The chance of reduced sleep quality was 11.6 times higher after moderate-to-severe COVID-19 infection than that after mild infection only in patients aged 26-59 years (95% confidence interval 1.42–94.32, p = 0.007).Conclusion. The chance of worsening sleep quality was significantly higher after a moderate-to-severe COVID-19 infection than after mild infection in 26-59-year-old old patients. At the same time, RLS was the most common post-COVID sleep disorder according to our study. Given the importance of sleep disorders, working-age patients after moderate-to-severe COVID-19 infection require active monitoring by doctors in order to timely correct emerging complaints.

Prevalence and predictors of restless legs syndrome in non-pregnant Saudi women of childbearing age.

This study assessed the prevalence of restless legs syndrome (RLS) and its correlates and severity among non-pregnant Saudi women of childbearing age. Consecutive non-pregnant female visitors (age 15-44 years) of the primary care centers of the female University campus at King Saud University (n = 1,136) were interviewed face-to-face to determine the presence and severity of RLS using the International Restless Legs Syndrome (IRLS) Study Group criteria and IRLS severity scale. A total of 271 participants (24%) were diagnosed with RLS. Of these cases, severe/very severe RLS was diagnosed in 13% and mild/moderate in 87%. None of these participants had been diagnosed or treated for RLS before. Subjects with RLS were older, had a higher body mass index, and a higher prevalence of vitamin D deficiency and diabetes mellitus than those without RLS. Multivariate binary logistic regression analysis identified the following independent predictors of RLS: age (OR 1.03 [1.009-1.051], p = 0.004), vitamin D deficiency (OR 2.147 [1.612-2.86], p < 0.001), and diabetes mellitus (OR 4.408 [1.946-9.982], p < 0.001). Our results indicate that RLS is very common and underdiagnosed among non-pregnant Saudi women of a childbearing age-attending primary care cents. RLS was linked to age, vitamin D deficiency, and diabetes mellitus.

Impact of Positive Airway Pressure on International Restless Legs Syndrome Score in Sleep Disordered Breathing.

Study Objective: Studies have shown increased prevalence of restless legs syndrome (RLS) in sleep disordered breathing (SDB), however limited data have focused on the impact of SDB therapy on RLS. We hypothesize that positive airway pressure (PAP) will improve the International Restless Legs Syndrome (IRLS) score among SDB patients compared to patients without PAP. Methods: Patients with AHI ≥ 5 who responded positively to a RLS qualifier question from January 2010 to May 2015 were included in this retrospective study. IRLS score was used to measure RLS symptom severity. Two-sample t-tests and one-way analysis of variance were used to compare changes in IRLS score and linear regression models were created to examine IRLS change with PAP use and PAP adherence (PAP usage ≥4 h nightly for ≥70% of nights), adjusting for potential confounders. Results: In 434 patients (51.9 ± 13.4years, 50.5% female, 77.6% Caucasian; 325 PAP, 109 control), IRLS scores improved from baseline to follow-up, with the PAP group achieving significant improvement after adjustment for covariates (difference in IRLS: −1.8 (CI −3.6,0.00), p = 0.050). In self-reported PAP adherent patients, IRLS improvement was greater than controls (−5.3 ± 7.4 vs. −2.7 ± 7.6 respectively, p = 0.045), and comparable to non-adherent patients (−5.3 ± 7.4 vs. −3.0 ± 7.0, p = 0.091). Conclusions: Among SDB patients with a positive RLS qualifier, those who used PAP therapy achieved significantly greater improvement in IRLS scores than patients who did not use PAP, with more significant changes in the PAP adherent group. This is the first large clinical study to examine these relationships, providing a basis for future prospective interventional trials and informing clinicians of expected improvement in IRLS score in PAP treated SDB populations.

Treatment of Leg Veins for Restless Leg Syndrome: A Retrospective Review.

Background: Restless leg syndrome (RLS) and chronic venous insufficiency (CVI) share similar circadian timings and epidemiological characteristics.Objective: The objective of the study was to investigate whether treating superficial venous reflux (SVR) improves the RLS severity in patients with CVI and whether there is an association of the RLS severity with the number of refluxed veins.Materials and methods: Patients with RLS and duplex ultrasound-proven SVR were identified from a database of 134 patients. All patients underwent endovenous radiofrequency ablation and ultrasound-guided foam sclerotherapy. International RLS (IRLS) rating scale questionnaires were reviewed to assess pre- and post-intervention RLS status.Results: Thirty-five patients were identified. The average baseline IRLS score was 19.83 (moderate RLS) and improved to 7.89 (mild RLS) after treatment (p < .0001), corresponding to 63% decrease in symptoms. Ten patients (29%) had a follow-up score of 0, indicating complete relief of RLS symptoms. Twenty patients (57%) had decreased IRLS scores of 10 points or more (i.e. 1 grade level of severity). Six patients had no improvement. There was no association of the RLS severity with the number of refluxed veins.Conclusion: The study found that correcting SVR improves RLS symptoms, suggesting an association between CVI and RLS. Venous ultrasound study and intervention should be considered for potential patients.

Restless legs syndrome and quality of life in chronic hemodialysis patients.

Restless legs syndrome (RLS) is a sensorimotor disorder that often has a profound impact on sleep and one of the most troublesome conditions experienced in hemodialysis patients. Aims: The aim of study was to search frequency of RLS and effects of RLS on quality of life (QoL) in chronic hemodialysis patients. Chronic hemodialysis patients of classical hemodialysis units were chosen. Length of the study was approximately 1 year. Two hundred and thirty-seven patients were investigated. RLS was diagnosed using to international the RLS questionnaire. The International RLS (IRLS) rating scale was used to calculate RLS severity. QoL was assessed using the World Health Organization QoL brief version (WHOQOL-BREF) instrument. Student's t-test, Chi-square test or Fisher's exact test, Bonferroni correction for multiple comparisons, and Pearson or Spearman correlation analysis were used. Significance level was P < 0.05. Results: The overall prevalence of RLS according to the four essential criteria was 18.6% (n = 44). According to IRLS, 22.7% of the patients with RLS were mild (n = 10), 63.6% were moderate (n = 28), and 13.7% were severe (n = 6). The parameters of QoL were compared in RLS-positive and negative patients. There was no significant difference in psychological health (P = 0.971), social relationships (P = 0.462), and environment (P = 0.483) between two groups. Only the physical health scores were higher in without RLS than patients with RLS (P = 0.027). This study revealed that the frequency of RLS among chronic hemodialysis patients is 18.6% and RLS leads to physical life quality disturbances.

The Impact of Self-Reported Sleep on Caesarean Delivery in Women Undergoing Induction of Labour: A Prospective Study

216 women admitted for labour induction were recruited to evaluate sleep duration and other sleep measures on Caesarean delivery risk. The Pittsburgh Sleep Quality Index, Berlin (Obstructive Sleep Apnoea (OSA), Epworth Sleepiness Scale, International Restless Leg Syndrome, Insomnia Symptom Questionnaires were applied. Short sleep duration was defined as reported night sleep length in the previous month below the study population median of 6 hours. After binomial analysis, Caesarean delivery after labour induction is associated with short sleep duration (RR 1.8, 95% CI 1.1-2.9, P = 0.018), nulliparity, Bishop Score, prepregnant BMI and birth weight at P < 0.05. After adjustment for nulliparity, Bishop Score, prepregnant BMI and birth weight, short sleep duration remains independently predictive of Caesarean delivery AOR 2.4, 95% CI 1.1-5.0, P = 0.026. Women at high risk for OSA has a non-significant result on binomial analysis, RR 1.6, 95% CI 1.0-2.7, P = 0.073. In a sensitivity analysis which includes OSA in the multivariable logistic regression model, OSA’s predictive effect is attenuated AOR 1.2, 95% CI 0.4-3.2, P = 0.782 whilst short sleep duration remains significant AOR 2.3 95% CI 1.0-5.1, P = 0.039. Other evaluated sleep measures are not predictive of Caesarean delivery.

A method to switch from oral dopamine agonists to rotigotine in patients with restless legs syndrome and mild augmentation

BackgroundWe examined the short- and long-term efficacy and tolerability of a cross-titration algorithm from oral dopamine agonists to the rotigotine transdermal patch in patients dissatisfied with their restless legs syndrome (RLS) treatment, predominantly with mild augmentation. MethodsPatients with RLS (n = 20) were recruited at a single site. The cross-titration consisted of decreasing oral dopaminergic agents (ropinirole by 1 mg or pramipexole by 0.25 mg) and increasing rotigotine by 1 mg every two days. Efficacy and adverse events (AEs) were assessed at one, three, six and 12 months after the switch. ResultsPatients had moderate–severe RLS symptoms at the baseline (mean international restless legs syndrome (IRLS) score 19.4 ± 5.5); 85% had augmentation and 45% reported afternoon RLS symptoms. The baseline mean pramipexole equivalent dose was 0.6 ± 0.3 mg. At Week 5, 85% (17/20) had successfully switched from their oral dopamine agonist to rotigotine (mean dose 2.5 ± 0.6 mg; change in IRLS score: −6.7 ± 8.4, p = 0.002); 14 patients were CGI-I responders (much or very much improved). Three patients withdrew due to lack of efficacy. Twelve months after cross-titration, 10 patients continued on rotigotine, of whom four required either higher doses of rotigotine or supplemental RLS medication compared with their optimal Week 5 dose; five patients withdrew due to AEs and two due to lack of efficacy. ConclusionA cross-titration to rotigotine was efficacious after five weeks in 70% of patients dissatisfied with RLS treatment, most of whom had mild augmentation. At one year following the medication switch, 50% had discontinued rotigotine due to lack of continued efficacy or side effects.

Effect of governor moxibustion for restless legs syndrome of maintenance hemodialysis:a rando-mized controlled trial

To observe the effect of governor moxibustion for restless legs syndrome(RLS) of maintenance hemodialysis. Sixty-nine patients with RLS of maintenance hemodialysis were randomly divided into an observation group(34 cases) and a control group(35 cases). Conventional hemodialysis was applied in the two groups. Moxibustion was used at the governor vessel from Dazhui(GV 14) to Yaoshu(GV 2) separated by governor moxibustion powder and ginger mud in the observation group. Treatment was given once two weeks and continuous eight times were taken as a course. One course was adopted. Scores of international restless legs syndrome(IRLS) and Pittsburgh sleep quality index(PSQI) were observed before and after treatment and comprehensive effects were evaluated in the two groups. The total scores of IRLS and PSQI were decreased after treatment in the two groups(all P<0.01). And the above two scores after treatment of the observation group were apparently lower than those of the control group(both P<0.05). The cured and effective rate of the observation group was 58.8%(20/34),and that of the control group was 22.9%(8/35),with statistical difference(P<0.01). Governor moxibustion can effectively improve the symptoms and sleep quality of RLS of maintenance hemodialysis.

Post Hoc Analysis of Data from Two Clinical Trials Evaluating the Minimal Clinically Important Change in International Restless Legs Syndrome Sum Score in Patients with Restless Legs Syndrome (Willis-Ekbom Disease).

Determine the minimal clinically important change (MCIC), a measure determining the minimum change in scale score perceived as clinically beneficial, for the international restless legs syndrome (IRLS) and restless legs syndrome 6-item questionnaire (RLS-6) in patients with moderate to severe restless legs syndrome (RLS/Willis-Ekbom disease) treated with the rotigotine transdermal system. This post hoc analysis analyzed data from two 6-mo randomized, double-blind, placebo-controlled studies (SP790 [NCT00136045]; SP792 [NCT00135993]) individually and as a pooled analysis in rotigotine-treated patients, with baseline and end of maintenance IRLS and Clinical Global Impressions of change (CGI Item 2) scores available for analysis. An anchor-based approach and receiver operating characteristic (ROC) curves were used to determine the MCIC for the IRLS and RLS-6. We specifically compared "much improved vs minimally improved," "much improved/very much improved vs minimally improved or worse," and "minimally improved or better vs no change or worse" on the CGI-2 using the full analysis set (data as observed). The MCIC IRLS cut-off scores for SP790 and SP792 were similar. Using the pooled SP790+SP792 analysis, the MCIC total IRLS cut-off score (sensitivity, specificity) for "much improved vs minimally improved" was -9 (0.69, 0.66), for "much improved/very much improved vs minimally improved or worse" was -11 (0.81, 0.84), and for "minimally improved or better vs no change or worse" was -9 (0.79, 0.88). MCIC ROC cut-offs were also calculated for each RLS-6 item. In patients with RLS, the MCIC values derived in the current analysis provide a basis for defining meaningful clinical improvement based on changes in the IRLS and RLS-6 following treatment with rotigotine.

Open-label study of the efficacy and safety of intravenous ferric carboxymaltose in pregnant women with restless legs syndrome

ObjectiveThe objective of this study was to test the efficacy and safety of intravenous ferric carboxymaltose (FCM) in pregnant women with restless legs syndrome (RLS) and iron deficiency or anemia. The open-label pilot study (exploratory) was performed at the University Hospital of Zürich and the Neurocenter of Southern Switzerland (Lugano). Patient and MethodsNineteen women in the third trimester of pregnancy with moderate-to-severe RLS and serum ferritin levels <35 µg/l or hemoglobin (Hb) < 11.0 g/dl were included in the study. RLS was graded according to the International Restless Legs Syndrome (IRLS) Study Group rating scale. All participants had a score of ≥20 or had RLS ≥3 times/week. Based on the Hb levels, 500 or 700 mg of FCM was administered over 20 min. The primary end point was a ≥ 50% reduction in the mean IRLS score one week after FCM infusion. The secondary end points included periodic limb movements (PLMs; assessed using nocturnal foot actigraphy), sleep quality (assessed using the Pittsburgh Sleep Quality Index), and safety. ResultsThe IRLS score decreased from 23 ± 7 (baseline) to 13 ± 7 (P < 0.01), whereas the PLM index decreased from 35 ± 26 (baseline) to 25 ± 20 (P < 0.001). Significant improvement in sleep quality was also reported (P < 0.029), and treatment was well tolerated. Three serious adverse events were reported, but they were considered unrelated to treatment. ConclusionsThese data provide promising evidence on the safety and efficacy of FCM for moderate-to-severe RLS in pregnant women with iron deficiency or anemia. Therefore, a future placebo-controlled study is warranted.

Rotigotine in the treatment of primary restless legs syndrome: A meta-analysis of randomized placebo-controlled trials.

The aim of this study was to summarize the efficacy and tolerability of rotigotine in the treatment of primary restless legs syndrome (RLS). PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for English-language randomized controlled trials (RCTs) that assessed the effectiveness of rotigotine for RLS. The pooled mean change from baseline in International RLS (IRLS) Study Group Rating Scalescore and relative risk (RR) of response based on the Clinical Global Impression-Improvement (CGI-I) scale score were applied to evaluate the outcomes. The pooled proportions of adverse events (AEs) were also estimated. Six RCTs were included. The meta-analysis showed a favorable effectiveness of rotigotine versus placebo on RLS [mean change on IRLS score: mean difference (MD)=-4.80; 95% confidence interval (CI): -5.90 to -3.70; P<0.00001 and RR of response on CGI-I was 2.19; 95% CI: 1.86 to 2.58, P<0.00001]. The most common AEs were application site reactions, nausea, headache and fatigue. In general, rotigotine was well-tolerated in patients with primary RLS. Based on the findings from the meta-analysis, rotigotine was more significantly efficacious in the treatment of RLS than placebo. Nevertheless, long-term studies and more evidence of comparisons of rotigotine with other dopamine agonists are needed.

Effect of prior exposure to dopamine agonists on treatment with gabapentin enacarbil in adults with moderate-to-severe primary restless legs syndrome: pooled analyses from 3 randomized trials.

BackgroundDopamine agonists (DAs) are a first-line therapy for moderate-to-severe restless legs syndrome (RLS), but these treatments may lead to complications, such as augmentation and impulse control disorders, requiring switching to another therapeutic class. Here we assess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with moderate-to-severe primary RLS, with or without prior DA exposure.MethodsData from 3 trials were pooled. Patients were identified as DA-naive or DA-exposed, based on prior treatment with ropinirole, pramipexole, rotigotine, or pergolide mesylate, and the dopamine precursor levodopa. Details on prior treatment duration and dose were unavailable. Patients with a history of augmentation were excluded. Within DA-naive/DA-exposed patients we investigated the co-primary end points from the pivotal trials: mean change from baseline to week 12 in International RLS (IRLS) Rating Scale total score and proportion of responders (“much”/“very much” improved) on the investigator-rated Clinical Global Impression–Improvement (CGI-I) scale. Safety was also assessed.Results671 patients were randomized (DA-naive: placebo, n = 194; GEn 600 mg, n = 131; GEn 1200 mg, n = 214; DA-exposed: placebo, n = 50; GEn 600 mg, n = 30; GEn 1200 mg, n = 52). Across treatment arms, no significant differences between DA-naive and DA-exposed subgroups in IRLS Rating Scale total score change from baseline at any visit were seen, except week 1 in the placebo group (−6.1 DA-naive vs −3.4 DA-exposed, P = .020). No significant differences in the odds of CGI-I response at week 12 between DA-naive vs DA-exposed patients in any treatment group were seen; however, with placebo there was a nonsignificant trend toward fewer responders among DA-exposed (34.0%) vs DA-naive (44.3%) patients. Both GEn doses significantly improved the IRLS Rating Scale total score change from baseline and CGI-I response vs placebo, regardless of prior DA exposure. The most common treatment-emergent adverse events were dizziness and somnolence.ConclusionsPrior DA exposure had no significant effect on efficacy or tolerability of GEn (600 or 1200 mg) in this pooled analysis of adults with moderate-to-severe primary RLS. These data support the use of GEn in DA-exposed and DA-naive patients.Trial registrationClinicalTrials.gov NCT00298623, NCT00365352, and NCT01332305

Sleep patterns and sleep disturbances across pregnancy

ObjectiveThis study sought to characterize sleep patterns and sleep problems in a large sample of women across all months of pregnancy. MethodsA total of 2427 women completed an Internet-based survey that included the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, vitality scale of the Short Form 36 Health Survey (SF-36), Insomnia Severity Index (ISI), Berlin questionnaire, International Restless Legs Syndrome (IRLS) question set, and a short version of the Pregnancy Symptoms Inventory (PSI). ResultsAcross all months of pregnancy, women experienced poor sleep quality (76%), insufficient nighttime sleep (38%), and significant daytime sleepiness (49%). All women reported frequent nighttime awakenings (100%), and most women took daytime naps (78%). Symptoms of insomnia (57%), sleep-disordered breathing (19%), and restless legs syndrome (24%) were commonly endorsed, with no difference across the month of pregnancy for insomnia, sleep-disorder breathing, daytime sleepiness, or fatigue. In addition, high rates of pregnancy-related symptoms were found to disturb sleep, especially frequent urination (83%) and difficulty finding a comfortable sleep position (79%). ConclusionsWomen experience significant sleep disruption, inadequate sleep, and high rates of symptoms of sleep disorder throughout pregnancy. These results suggest that all women should be screened and treated for sleep disturbances throughout pregnancy, especially given the impact of inadequate sleep and sleep disorders on fetal, pregnancy, and postpartum outcomes.

Pregabalin Calms Restless Legs by Unknown Mechanism

Oral pregabalin (Lyrica) significantly improved symptoms of moderate to severe restless leg syndrome (RLS), compared with both placebo and pramipexole, in an industry-sponsored, international randomized trial. Also, pregabalin was associated with significantly less worsening of symptoms than was pramipexole, Richard P. Allen, PhD, of the department of neurology at Johns Hopkins University, Baltimore, and his associates reported in the New England Journal of Medicine. Pregabalin also was associated with lower rates of nausea, vomiting, and headache than pramipexole, but patients taking pregabalin had higher rates of suicidal ideation, dizziness, somnolence, and weight gain – “factors that may limit its long-term use,” the investigators said. Dopaminergic drugs such as pramipexole are known to be associated with augmentation in which symptoms intensify and may involve more parts of the body and start earlier in the day than before treatment, so researchers have been searching for an alternative medication. Pregabalin is a nondopaminergic agent with analgesic and anticonvulsant activity. Dr. Allen and his colleagues assessed both agents in a study involving 719 adults with moderate to severe primary RLS who were treated and followed at 102 medical centers in the United States and Europe. In the double-blind trial sponsored by Pfizer, these patients were randomly assigned to receive 0.25 mg pramipexole, 0.5 mg pramipexole, 300 mg pregabalin, or matching placebo capsules every day for 12 weeks. At that time, all patients receiving placebo were randomly reassigned to one of the three active treatments for the remainder (40 weeks) of the 1-year study. At 12 weeks, patients who received pregabalin showed significantly greater improvement in International RLS (IRLS) Study Group Rating Scale scores than did those who received placebo. Patients who received pregabalin also reported greater improvement in waking after sleep onset, quality of sleep, number of nightly awakenings, and total sleep time. These measures also were significantly better for patients treated with 0.5 mg pramipexole when compared with placebo-treated patients, but not for those taking 0.25 mg pramipexole. In a noninferiority assessment, pregabalin outperformed both doses of pramipexole on reduction in IRLS score at both 12 weeks and 52 weeks. The finding that pregabalin is effective for RLS even though it has no direct effect on dopaminergic systems calls into question the rationale for dopaminergic therapies. Dopaminergic treatments have been predicated on the assumption that RLS results primarily from dopamine abnormalities, Dr. Allen and his associates noted (N. Engl. J. Med. 2014;370:621–631). A total of 50 serious adverse events occurred in 37 patients: 16 events in the pregabalin group, 22 events in the lower-dose pramipexole group, and 12 events in the higher-dose pramipexole group. This included 11 cases of suicidal ideation: 6 in the pregabalin group, 3 in the lower-dose pramipexole group, and 2 in the higher-dose pramipexole group. Editor's NoteLooks like Lyrica will be seeking Food and Drug Administration approval for restless leg syndrome, and it looks like it works reasonably well, with a different set of side effects from those seen with dopaminergic agents.It's a bit puzzling that a GABA-ergic drug would work for this condition. But benzodiazepines are often used with decent utility for restless legs. And if pregabalin works, maybe the much less expensive, noncontrolled, neurochemically similar drug gabapentin might be worth a try. That would be off label, of course, but for someone suffering with severe restless leg syndrome and limited response or intolerance of usual drugs, I'd consider it.— Karl Steinberg, MD, CMDEditor in Chief Looks like Lyrica will be seeking Food and Drug Administration approval for restless leg syndrome, and it looks like it works reasonably well, with a different set of side effects from those seen with dopaminergic agents. It's a bit puzzling that a GABA-ergic drug would work for this condition. But benzodiazepines are often used with decent utility for restless legs. And if pregabalin works, maybe the much less expensive, noncontrolled, neurochemically similar drug gabapentin might be worth a try. That would be off label, of course, but for someone suffering with severe restless leg syndrome and limited response or intolerance of usual drugs, I'd consider it. — Karl Steinberg, MD, CMD Editor in Chief