普拉克索治疗原发性不宁腿综合征的疗效和安全陛观察

目的 观察普拉克索对我国原发性不宁腿综合征(RLS)患者的治疗效果以及可能发生的不良反应. 方法 选择自2009年5月至11月在哈尔滨医科大学第二附属医院神经内科就诊的10例中到重度原发性RLS患者,给予普拉克索0.125～0.75mg/d,每日睡前2～3h顿服,持续治疗6周.利用国际RLS研究小组的RLS严重程度量表(mLS)、临床总体印象改善量表(CGI-I)、患者总体印象量表(PGI)和Epworth嗜睡量表(ESS)对患者治疗前后的RLS症状严重程度和嗜睡程度进行评估.并对结果进行统计学分析,同时记录不良反应.结果 (1)治疗后患者的IRLS评分较治疗前平均降低73.7%,比较差异有统计学意义(P<0.05),9例患者IRLS评分降低在50%以上;(2)治疗结束时,8例患者PGI评估选择"很好"或"非常好",9例患者CGI-I评估为"明显改善"或"非常明显改善";(3)患者ESS评分在治疗后较治疗前平均降低3.80±1.75,比较差异有统计学意义(P<0.05);(4)1例患者在治疗末期加量至0.5mg/d时出现轻度恶心,胃区不适,治疗结束停药2 d后症状自行消失;(5)1例患者首次用药后双下肢感觉异常和睡眠障碍即有明显改善.结论 为期6周的临床实验表明,在每日口服剂量为0.125～0.75 mg时,普拉克索对于我国原发性RLS的治疗是安全有效的.     

Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study).

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study.     

Efficacy and safety of pramipexole in restless legs syndrome

OBJECTIVE: To evaluate the efficacy and safety of pramipexole in patients with moderate to severe restless legs syndrome (RLS) METHODS: The authors conducted a 12-week, double-blind, randomized, placebo-controlled trial of fixed doses of pramipexole (0.25, 0.50, and 0.75 mg/day). Patients (N = 344) were up-titrated to their randomized dose over 3 weeks. The primary efficacy endpoints were patient ratings of symptom severity on the International RLS Study Group Rating Scale (IRLS) and clinician ratings of improvement on the Clinical Global Impressions-Improvement (CGI-I) scale. Secondary efficacy endpoints included visual analogue ratings of sleep and quality of life (QOL) RESULTS: By both primary measures, pramipexole was superior to placebo. For IRLS, the adjusted mean (SE) change from baseline to week 12 was -9.3 (1.0) for placebo, -12.8 (1.0) for 0.25 mg/day, -13.8 (1.0) for 0.50 mg/day, and -14.0 (1.0) for 0.75 mg/day (all p < 0.01). Similarly, pramipexole increased the percentage of patients with a CGI-I rating of "very much improved" or "much improved" at the end of the trial (51.2% for placebo and 74.7%, 67.9%, and 72.9% for pramipexole; all p < 0.05). Pramipexole significantly improved ratings of symptom severity, day and night, and also ratings of sleep satisfaction and QOL. Pramipexole was well tolerated: The most frequent adverse events with higher occurrence in the pramipexole group were nausea (19.0% vs 4.7%) and somnolence (10.1% vs 4.7%) CONCLUSION: As rated by patients and by clinicians, pramipexole was efficacious and safe in reducing the symptoms of restless legs syndrome.     

Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel-group, placebo-controlled study.

Restless legs syndrome (RLS) is a neurological condition with significant impact on sleep and quality of life (QoL). This double-blind, randomized, 12-week, multinational study compared the efficacy and safety of ropinirole and placebo in RLS. In total, 267 outpatients with moderate-to-severe RLS were randomly assigned to ropinirole (0.25-4.0 mg/day) or placebo, 1 to 3 hours before bedtime. The primary endpoint was the change in International Restless Legs Scale (IRLS) score at week 12. Key secondary endpoints were the percentage of patients showing significant improvement on the Clinical Global Impression-Improvement (CGI-I) scale at week 12 and changes in IRLS and CGI-I scale scores at week 1. Other measures included the Medical Outcomes Study sleep scale and Restless Legs Syndrome Quality of Life questionnaire. Improvements were significantly greater for ropinirole than placebo for change in IRLS score at week 12 (-11.2 [SE 0.76] vs. -8.7 [0.75], respectively; adjusted treatment difference -2.5 [95% confidence interval [CI], -4.6, -0.4], P = 0.0197); all key secondary endpoints; sleep and QoL parameters. Adverse events were typical for dopamine agonists; disease augmentation, although not directly assessed, was not reported during treatment. Ropinirole improves symptoms, associated sleep disturbance, and QoL of RLS patients and is generally well tolerated.     

Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole in the treatment of restless legs syndrome

OBJECTIVE: In the absence of comparative trials a meta-analysis was performed to compare the efficacy and tolerability of the non-ergot derived dopamine agonists, pramipexole and ropinirole, in restless legs syndrome (RLS). METHODS: Frequentist fixed and random-effects models were pre-specified for the direct comparisons and a Bayesian approach for the indirect comparison. Efficacy outcomes included the mean change from baseline in the International RLS Study Group Rating Scale (IRLS) score and the percentage of responders on the clinical global impressions - improvement scale (CGI-I). Safety outcomes included the incidence of withdrawal and adverse events. RESULTS: The direct meta-analysis confirmed superior efficacy for both treatments versus placebo for the IRLS (pramipexole: -5.45; 95% CI: -7.70; -3.20; ropinirole: -3.16; 95% CI: -4.26; -2.05) and the CGI-I (pramipexole: OR=2.98; 95% CI: 2.08; 4.26; ropinirole: OR=1.99; 95% CI: 1.52; 2.60). Placebo comparisons showed a significantly higher incidence of nausea for pramipexole (p<0.01), whereas nausea, vomiting, dizziness, and somnolence were significantly higher for ropinirole (all p<0.01). The indirect comparison showed with a probability of > or = 95%, a superior reduction in the mean IRLS score (-2.33; 95% credibility interval [CrI]: -4.23; -0.41), higher CGI-I response rate (OR=1.50; 95% CrI: 0.97; 2.32) and significantly lower incidence of nausea, vomiting, and dizziness for pramipexole compared to ropinirole. CONCLUSION: Differences in efficacy and tolerability favouring pramipexole over ropinirole can be observed. These findings should be further confirmed in head-to-head clinical trials.     

Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study--the PRELUDE study

BACKGROUND AND PURPOSE: To evaluate the effects of pramipexole (0.125-0.75 mg/d) on polysomnographic (PSG) measures and patient and clinician ratings of restless legs syndrome (RLS). PATIENTS AND METHODS: Patients (n=109) with moderate to severe RLS were randomized to placebo or fixed doses of pramipexole during a 3-week, double-blind, placebo-controlled, dose-finding study. RESULTS: In each pramipexole dose group, the periodic limb movements during time in bed index (PLMI) decreased significantly, compared with placebo (adjusted mean difference in log-transformed data: 0.125 mg, -1.54; 0.25 mg, -1.93; 0.50 mg, -1.89; and 0.75 mg, -1.52; P<0.0001). At all doses, International RLS Study Group Rating Scale (IRLS) scores were also significantly reduced, with the greatest adjusted mean reduction in the 0.50mg group (-17.01). At all but the lowest pramipexole dose, the percentage of responders (> or =50% reduction of IRLS score) was substantially higher than for placebo (61.9-77.3, vs 33.3%). In the pramipexole groups, 50.0-77.3% of patients rated their condition as 'much better' or 'very much better', compared with 38.1% of patients in the placebo group (P=0.0139 for the 0.50 mg dose). Clinical global impressions (CGI) scale ratings of 'much improved' or 'very much improved' were given to 61.9-86.4% of patients in the pramipexole groups, compared with 42.9% in the placebo group (P<0.05 for the 0.25, 0.50, and 0.75 mg groups). Pramipexole was well tolerated and did not produce somnolence at any dose. CONCLUSION: Pramipexole is effective and safe in the treatment of both objective and subjective facets of RLS.     

Long-term efficacy and safety of gabapentin enacarbil in Japanese restless legs syndrome patients

Several short- and long-term studies conducted in Europe/North America have demonstrated good efficacy and tolerability of 600-1800 mg gabapentin enacarbil (GEn). However, no studies have evaluated the efficacy of long-term treatment with GEn in Asian patients. Therefore, the objective of this study was to evaluate the efficacy and safety of long-term treatment with GEn in Japanese patients with restless legs syndrome (RLS) in a multicenter open-label study. RLS patients aged 20-80 years were allocated to receive oral GEn 1200 mg/day for a treatment period of 52 weeks. International Restless Legs Syndrome Scale (IRLS) score, investigator- and patient-rated Clinical Global Impression (CGI) scores, Pittsburgh Sleep Quality Index (PSQI) total scores and subscores, and short form (SF)-36 subscores were assessed, and adverse events (AEs) were monitored. In 181 patients (mean age, 54.9±12.2 years; BMI, 23.0±2.6 kg/m2) IRLS score decreased from 24.4±0.4 at baseline to 6.3±0.6 at week 52, with a reduction of -18.0±0.6. The IRLS responder rate was 80.3% at week 52. ICGI and PCGI responder rates were 87.1% and 87.1%, respectively. PSQI and SF-36 also showed significant improvements. AEs were reported in 96.2% of patients but remained mild-to-moderate in nearly all the cases. Serious AEs occurred in 1.6%. Dizziness and somnolence were noted in 46.2% and 41.2% of patients, respectively, and mostly occurred during the first 4 weeks. No episodes of augmentation were reported. In conclusion, long-term treatment with GEn improved RLS symptoms as well as investigator- and patient-reported outcomes in Japanese patients with moderate-to-severe RLS, with an acceptable safety profile. Randomized, double-blind, placebo/active-controlled trials are desirable to confirm these preliminary results.     

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.     

Ropinirole is effective in the long-term management of restless legs syndrome: a randomized controlled trial.

The objective of this study was to investigate the long-term efficacy of ropinirole in patients with restless legs syndrome (RLS) and to assess the potential for relapse after the discontinuation of active treatment. Patients with primary RLS (n = 202) received single-blind ropinirole for 24 weeks. Patients meeting treatment continuation criteria were randomized to double-blind treatment with ropinirole or placebo for a further 12 weeks. The primary efficacy variable was the proportion of patients relapsing during double-blind treatment. Additional efficacy measures included time to relapse, withdrawals due to lack of efficacy, improvement on the Clinical Global Impression-Improvement (CGI-I) scale, change in International Restless Legs Scale (IRLS) score during double-blind treatment, and changes in sleep and quality of life (QoL) parameters. Significantly fewer patients relapsed on ropinirole than on placebo (32.6% vs. 57.8%; P = 0.0156). Time to relapse was longer with ropinirole and more patients withdrew due to lack of efficacy with placebo. Patients showed improvements in IRLS and CGI-I scores, sleep and QoL parameters with single-blind ropinirole, which were better maintained when ropinirole was continued during the double-blind phase, but reduced with placebo. Ropinirole was well tolerated; adverse events were typical for dopamine agonists. Ropinirole was highly effective and well tolerated in the long-term management of RLS, with pharmacological effect over 36 weeks.     

Pramipexole for Chinese people with primary restless legs syndrome: a 12-week multicenter,randomized, double-blind study

BackgroundRestless legs syndrome (RLS) often responds to agents that enhance dopamine neurotransmission. The present 12-week study aimed to evaluate the efficacy and adverse events of pramipexole (PPX) for the treatment of adult, Chinese people with primary RLS.MethodsA total of 204 Chinese people with RLS were randomly assigned to receive either the placebo or PPX (flexibly titrated from 0.25 mg to 0.75 mg), 2 h to 3 h before bedtime for 12 weeks. The primary measuring outcomes were the International RLS Study Group Rating Scale (IRLS) and the Clinical Global Impressions-Improvement (CGI-I) scale. The secondary outcome was adverse events.ResultsOne hundred and ninety participants completed the study. At 12 weeks, the adjusted mean (SE) change from baseline was greater for PPX (vs placebo) for the IRLS score (−13.2 ± 0.7 vs −9.4 ± 0.6; p <0.01), and (−12.1 ± 0.6 vs −8.3 ± 0.6; p <0.01) at the end of one month follow-up after treatment. The CGI-I rating of “very much improved” or “much improved” in the percentage of participants (61.8% vs 34.3%; p <0.01), and (51.0% vs 26.5%; p <0.01) after week 12, and one month follow-up of treatment, respectively. The proportion of adverse events was 60.8% in the PPX group and 45.1% in the placebo group. No deaths related to PPX treatment were recorded.ConclusionsIn summary, the present study showed that PPX is efficacious and well tolerated in Chinese people with primary RLS.     

Clinical efficacy of ropinirole for restless legs syndrome is not affected by age at symptom onset

ObjectiveTo determine whether clinical response to the dopamine agonist, ropinirole, in the treatment of primary restless legs syndrome (RLS), depends upon the age-at-onset of RLS symptoms.MethodsPooled data from four 12-week, randomized, double-blind, placebo-controlled studies of ropinirole in patients with moderate-to-severe primary RLS were analyzed post hoc. The relationship between age-at-onset and response to treatment, based on change from the baseline International Restless Legs Syndrome Study Group (IRLSSG) rating scale (the International Restless Legs Scale [IRLS]) total score and the proportion of responders (rated ‘much’/‘very much’ improved) on the Clinical Global Impression–Improvement (CGI-I) scale, was explored.ResultsThe range of age-at-onset of RLS symptoms was 2–75 years. No relationship was observed between the age-at-onset of RLS symptoms and baseline IRLS total score (correlation r = −0.06), and between dose administered at Week 12 last observation carried forward (LOCF) and age-at-onset (r = −0.04). The age-at-onset by treatment interaction was non-significant (P = 0.952 for the IRLS and P = 0.716 for the CGI-I scale), indicating there was no significant relationship between age-at-onset and the magnitude of ropinirole treatment effect.ConclusionsThese data suggest that ropinirole provides effective relief of symptoms, regardless of age at RLS symptom onset.     

Sternberg working memory performance following treatment with pramipexole in patients with moderate-to-severe restless legs syndrome

ObjectivesWe recently reported that the P300 amplitude related to the Sternberg working memory (WM) task was significantly lower in drug-naïve severe restless legs syndrome (RLS) patients than controls. Here, we evaluated the effects of pramipexole on the Sternberg WM task performance by event-related potential (ERP) study.MethodsThirteen drug-naïve RLS patients (52.0 ± 9.48 years) were enrolled in the study. Pramipexole was administered over a period of 12 weeks every night 1 h before bedtime. Two ERP studies were carried out: the first was performed just before giving the first dose of pramipexole and the second was conducted at 12–16 weeks after commencement of pramipexole administration. P300 amplitudes and reaction times were compared before and after treatment considering brain regions and memory load as within-subject factors. Clinical and sleep-related variables were correlated with P300 amplitude.ResultsAfter treatment with pramipexole, the International RLS Severity Scale (IRLS) score was significantly decreased. Sleep quality and depression were also significantly improved. Omission error was significantly reduced without significant change of commission error. Reaction time was significantly shortened, regardless of memory load size, following treatment with pramipexole. Parietal P300 amplitude was significantly increased after treatment with pramipexole for all memory load sizes. Increase of frontal P300 amplitude was significantly correlated with improvement of sleep duration, IRLS, Insomnia Severity Index, and Pittsburgh Sleep Quality Index score.ConclusionOur study suggested that pramipexole improves WM performance in patients with RLS in addition to improving RLS symptoms, sleep disturbance, and depression.     

Efficacy of gabapentin enacarbil in adult patients with severe primary restless legs syndrome

AimAssess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with severe primary restless legs syndrome (RLS).MethodsWe pooled data from three 12-week, double-blind, placebo-controlled, randomized trials (NCT00298623, NCT00365352, NCT01332305) across GEn 600-mg, GEn 1200-mg, and placebo treatment groups for severe primary RLS (baseline International Restless Legs Scale (IRLS) total score ≥24). Co-primary end points at week 12 were mean change from baseline in IRLS total score and proportion of responders (“much”/very much” improved) on the investigator-rated Clinical Global Impression – Improvement (CGI-I) Scale. Outcomes for individual IRLS items (eg, sleep, mood, quality of life, pain, safety) were assessed.ResultsA total of 309 patients had severe primary RLS (placebo, n = 110; GEn 600 mg, n = 80; GEn 1200 mg, n = 119). GEn 600 mg and 1200 mg significantly improved least-squares mean IRLS total scores versus placebo at week 12 (placebo, −12.3; GEn 600 mg, −16.3; GEn 1200 mg, −18.0; treatment difference vs. placebo, both p <0.01). Significantly more patients with severe primary RLS treated with GEn 600 mg (64%) and 1200 mg (74%) were CGI-I responders at week 12 versus placebo (42%; p <0.01 for both GEn doses). Both GEn doses led to significant improvements in the other outcomes explored versus placebo at week 12. The most frequent treatment-emergent adverse events (TEAEs) were somnolence (GEn, 21–24%; placebo, 3%) and dizziness (GEn, 14–19%; placebo, 3%).ConclusionsGEn (600 mg or 1200 mg) once daily significantly improved RLS symptoms and consequences of these symptoms in severe primary RLS. The most frequent TEAEs were somnolence and dizziness.     

A 52-week open-label study of the long-term safety of ropinirole in patients with restless legs syndrome

OBJECTIVE: To assess the long-term safety and efficacy of ropinirole in the treatment of patients with restless legs syndrome (RLS) over 52 weeks. METHODS: A 52-week, multicentre, open-label continuation study involving 310 patients, conducted in 11 countries. Eligible patients from four parent studies were invited to participate. At parent study entry, all patients had a score of > or =15 on the International Restless Legs Scale (IRLS). In this continuation study, all participants received ropinirole, 0.25-4.0 mg once daily, for 52 weeks. The primary study objective was to evaluate the safety of ropinirole. Efficacy was assessed by change in IRLS score, as well as by global improvements (clinical global impression [CGI] scale) and improvements in measures of sleep, work productivity, and quality of life. RESULTS: Overall, 251 (81.0%) patients completed the study. The mean ropinirole dose at study end was 1.90 mg/day. A total of 282 patients (91.3%) reported > or = 1 adverse event. For the majority of patients, the reported adverse events were mild or moderate in intensity. The most common adverse event was nausea. Adverse events led to discontinuation in 8.7% of patients. At week 52, IRLS scores improved by an average of 12.0 points from baseline, and 82.8% of patients were 'much improved' or 'very much improved' on the CGI-improvement scale. Ropinirole treatment was also associated with improvements in measures of sleep and quality of life. CONCLUSIONS: Ropinirole was well tolerated and therapeutic efficacy was maintained over 52 weeks in patients with RLS.     

Transcranial direct current stimulation on primary sensorimotor area has no effect in patients with drug-naïve restless legs syndrome: a proof-of-concept clinical trial

ObjectiveTo evaluate the efficacy of transcranial direct current stimulation (tDCS) in people with drug-naïve restless legs syndrome (RLS).MethodsA two-week, double-blind, randomized, sham-controlled trial was performed. Thirty-three females with RLS were recruited. Participants received five sessions of tDCS using cathodal, anodal or sham stimulation. They were assessed at baseline (T0), three days (T1) and 13 days (T2) after the end of tDCS. Primary outcomes included the International RLS Group Rating Scale (IRLS) and the Clinical Global Impressions-Improvement (CGI-I). Secondary outcomes included the Patient Global Impression scale, the Pittsburgh Sleep Quality Index, the Medical Outcome Study sleep subscales, and the Beck Depression Inventory. Objective neurophysiological changes were assessed using event-related desynchronization/synchronization (ERD/ERS) of electroencephalography.ResultsThe changes in the IRLS scores, as well as the responder rate in the CGI-I scale, did not differ significantly among the groups. There was also no significant difference in any of the secondary outcome measures and ERD/ERS among the groups.ConclusionsTranscranial direct current stimulation with electrodes on the sensorimotor areas showed no significant effect in people with drug-naïve RLS.     

Relationship of periodic leg movements and severity of restless legs syndrome: a study in unmedicated and medicated patients.

OBJECTIVE: To evaluate the relationship of the severity of restless legs syndrome (RLS) as assessed by a subjective, patient-rated scale (International RLS Study Group Rating Scale, IRLS), and of periodic leg movements in sleep (PLMS) as an objective parameter, in two different patient populations. METHODS: Data of 200 unmedicated patients with idiopathic RLS were evaluated. Group 1 (n=100) consisted of selected patients participating in the Pergolide European Australian RLS (PEARLS) study. Group 2 (n=100) represented an outpatient RLS population investigated in a Sleep Disorders Center. Additionally, Group 1 was also evaluated after a 6 week double-blind treatment period, where 47 patients received pergolide and 53 patients placebo. RESULTS: In unmedicated patients, IRLS scores correlated with the PLMS-arousal index (r=0.22, p=0.033) but not with the PLMS index in Group 1 while no correlation was found in Group 2. The change of the IRLS score under treatment in Group 1 correlated significantly both with the change of the PLMS index (r=0.42, p<0.001) and the change of the PLMS-arousal index (r=0.38, p<0.001). CONCLUSIONS: The IRLS adequately reflects treatment changes of PLMS indices. In unmedicated patients, the IRLS correlates with PLMS indices probably only in selected RLS populations with predefined PSG criteria and high PLM activity. SIGNIFICANCE: The IRLS is an appropriate subjective rating scale for measuring treatment effects in RLS.     

Relation of the International Restless Legs Syndrome Study Group rating scale with the Clinical Global Impression severity scale,the restless legs syndrome 6-item questionnaire,and the restless legs syndrome-quality of life questionnaire

BackgroundThe SP790 study (ClinicalTrials.gov, NCT00136045) showed benefits of rotigotine over placebo in improving symptom severity of restless legs syndrome (RLS), also known as Willis-Ekbom disease, on the International Restless Legs Syndrome Study Group rating scale (IRLS), Clinical Global Impression item 1 (CGI-1), RLS 6-item questionnaire (RLS-6), and the RLS-quality of life questionnaire (RLS-QoL) in patients with moderate to severe idiopathic RLS. To provide clinical context for the IRLS and to guide the choice of assessment scales for RLS studies, our post hoc analysis of SP790 data evaluated associations between the IRLS and the CGI-1, IRLS and RLS-6, and the IRLS and RLS-QoL.MethodsScale associations were analyzed at baseline and at the end of maintenance (EoM) using data from the safety set (rotigotine and placebo groups combined [n = 458]). Changes from baseline to EoM in IRLS score vs comparator scale scores also were analyzed.ResultsThere was a trend towards increasing IRLS severity category with increasing CGI-1, RLS-6, and RLS-QoL score. Pearson product moment correlation coefficients showed correlations between IRLS and comparator scale scores at baseline and EoM as well as correlations for change from baseline to EoM.ConclusionCorrelations between the IRLS and comparator scales were substantial. These data indicate that the IRLS is clinically meaningful. The IRLS and CGI-1 are generally sufficient to evaluate the overall severity and impact of RLS symptoms in clinical trials.     

Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome

OBJECTIVE: Restless legs syndrome (RLS) is a distressing sensorimotor disorder with a 5% to 10% prevalence in the United States and Western Europe. The nocturnal occurrence of symptoms often leads to severe sleep disturbances. RLS has been reported to be associated with depression and anxiety. The aim of the present study was to investigate the relationship between RLS symptom severity, sleep disturbances, and depressive symptoms. METHOD: Questionnaire data from 100 consecutive patients with idiopathic RLS who had been investigated in our Sleep Disorders Unit from April 1999 to December 2004 were evaluated. Patients were untreated regarding RLS, depression, or sleep disturbances. Severity of RLS was assessed with the International RLS Study Group rating scale (IRLS). Depressive symptoms and subjective sleep quality were determined using the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI), respectively. RESULTS: IRLS scores indicated moderate-to-severe RLS symptoms in the population studied (mean +/- SD IRLS score = 23.6 +/- 6.7). The mean +/- SD BDI score was 9.3 +/- 5.6, with highest values on the "reduced sleep," "loss of energy," and "work difficulties" items, indicating predominating somatic symptoms of depression. Fourteen patients had a BDI score of 15 to 20 ("mild depression"), and 3 patients had a BDI score of 20 to 30 ("mild to moderate depression"). Overall, patients estimated their sleep quality as moderately impaired (mean +/- SD PSQI score = 10.9 +/- 3.7). Severity of RLS correlated with the impairment of subjective sleep quality (r = 0.281, p = .007) but not with self-rated depressive symptoms (r = 0.119, p = .237). CONCLUSION: RLS patients scored high on the somatic items of the BDI, particularly on those related to sleep disturbance, but not on the other items that mostly address cognitive symptoms. Our results indicate that RLS might be associated with some features of depression but not with the full spectrum of a depressive disorder. The relationship between the 2 disorders should be investigated in further studies.     

Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study

The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. This prospective, open-label 6-month study was conducted in six European countries and included 65 patients (85% treatment naive) with idiopathic RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence of augmentation was diagnosed independently by two international experts using established criteria. In addition to the augmentation severity rating scale (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS), clinical global impression (CGI)) were analyzed. Sixty patients provided evaluable data, 35 completed the trial and 25 dropped out. Augmentation occurred in 60% (36/60) of patients, causing 11.7% (7/60) to drop out. Median time to occurrence of augmentation was 71 days. The mean maximum dose of levodopa was 311 mg/day (SD: 105). Patients with augmentation compared to those without were significantly more likely to be on higher doses of levodopa (≥300 mg, 83 vs. 54%, P = 0.03) and to show less improvement of symptom severity (IRLS, P = 0.039). Augmentation was common with levodopa, but could be tolerated by most patients during this 6-month trial. Patients should be followed over longer periods to determine if dropout rates increase with time.