Treatment Of Restless Legs Syndrome Research Articles

Treatment of restless legs syndrome: An evidence‐based review and implications for clinical practice

Only in the last three decades, the restless legs syndrome (RLS) has been examined in randomized controlled trials. The Movement Disorder Society (MDS) commissioned a task force to perform an evidence-based review of the medical literature on treatment modalities used to manage patients with RLS. The task force performed a search of the published literature using electronic databases. The therapeutic efficacy of each drug was classified as being either efficacious, likely efficacious, investigational, nonefficacious, or lacking sufficient evidence to classify. Implications for clinical practice were generated based on the levels of evidence and particular features of each modality, such as adverse events. All studies were classed according to three levels of evidence. All Level-I trials were included in the efficacy tables; if no Level-I trials were available then Level-II trials were included or, in the absence of Level-II trials, Level-III studies or case series were included. Only studies published in print or online before December 31, 2006 were included. All studies published after 1996, which attempted to assess RLS augmentation, were reviewed in a separate section. The following drugs are considered efficacious for the treatment of RLS: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Drugs considered likely efficacious are rotigotine, bromocriptine, oxycodone, carbamazepine, valproic acid, and clonidine. Drugs that are considered investigational are dihydroergocriptine, lisuride, methadone, tramadol, clonazepam, zolpidem, amantadine, and topiramate. Magnesium, folic acid, and exercise are also considered to be investigational. Sumanirole is nonefficacious. Intravenous iron dextran is likely efficacious for the treatment of RLS secondary to end-stage renal disease and investigational in RLS subjects with normal renal function. The efficacy of oral iron is considered investigational; however, its efficacy appears to depend on the iron status of subjects. Cabergoline and pergolide (and possibly lisuride) require special monitoring due to fibrotic complications including cardiac valvulopathy. Special monitoring is required for several other medications based on clinical concerns: opioids (including, but not limited to, oxycodone, methadone and tramadol), due to possible addiction and respiratory depression, and some anticonvulsants (particularly, carbamazepine and valproic acid), due to systemic toxicities.

Acupuncture for restless legs syndrome.

Restless legs syndrome (RLS) is a common movement disorder for which patients may seek treatment with acupuncture. However, the benefits of acupuncture in the treatment of RLS are unclear and have not been evaluated in a systematic review until now. To evaluate the efficacy and safety of acupuncture therapy in patients with RLS. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007), MEDLINE (January 1950 to February 2007), EMBASE (January 1980 to 2007 Week 8), Chinese Biomedical Database (CBM) (1978 to February 2007), China National Knowledge Infrastructure (CNKI) (1979 to February 2007), VIP Database (1989 to February 2007), Japana Centra Revuo Medicina (1983 to 2007) and Korean Medical Database (1986 to 2007). Four Chinese journals, relevant academic conference proceedings and reference lists of articles were handsearched. Randomized controlled trials and quasi-randomized trials comparing acupuncture with no intervention, placebo acupuncture, sham acupuncture, pharmacological treatments, or other non-acupuncture interventions for primary RLS were included. Trials comparing acupuncture plus non-acupuncture treatment with the same non-acupuncture treatment were also included. Trials that only compared different forms of acupuncture or different acupoints were excluded. Two authors independently identified potential articles, assessed methodological quality and extracted data. Relative risk (RR) was used for binary outcomes and weighted mean difference for continuous variables. Results were combined only in the absence of clinical heterogeneity. Fourteen potentially relevant trials were identified initially, but twelve of them did not meet the selection criteria and were excluded. Only two trials with 170 patients met the inclusion criteria. No data could be combined due to clinical heterogeneity between trials. Both trials had methodological and/or reporting shortcomings. No significant difference was detected in remission of overall symptoms between acupuncture and medications in one trial (RR 0.97, 95% CI 0.76 to 1.24). Another trial found that dermal needle therapy used in combination with medications and massage was more effective than medications and massage alone, in terms of remission of unpleasant sensations in the legs (RR 1.36, 95% CI 1.06 to 1.75; WMD -0.61, 95% CI -0.96 to -0.26) and reduction of RLS frequency (WMD -3.44, 95% CI -5.15 to -1.73). However, there was no significant difference for the reduction in either the longest or the shortest duration of RLS (WMD -2.58, 95% CI -5.92 to 0.76; WMD -0.38, 95% CI -1.08 to 0.32). There is insufficient evidence to determine whether acupuncture is an efficacious and safe treatment for RLS. Further well-designed, large-scale clinical trials are needed.

Patient- and Physician-Rated Measures Demonstrate the Effectiveness of Ropinirole in the Treatment of Restless Legs Syndrome

To investigate the effect of twice-daily ropinirole in patients with early evening restless legs syndrome (RLS) symptoms, particularly focusing on the relationship of patient- and physician-rated assessment of treatment outcomes. In this multicenter, double-blind, randomized, 12-week, flexible-dose study, patients with primary RLS, with symptom onset no earlier than 5 PM and a baseline International Restless Legs Syndrome Study Group Rating Scale (IRLS) total score > or = 20 received ropinirole 0.5 to 6.0 mg/d twice daily in equally divided doses, or placebo. First dose was 1 hour before the usual onset of symptoms; second dose was 3 to 8 hours after the first. Primary end point: change from baseline in IRLS total score at week 12 last observation carried forward (LOCF). Key secondary end points: proportion of responders (rated "very much improved" or "much improved") on the Clinical Global Impression-Improvement and the Patient Global Improvement scales. Improvements in IRLS total score were statistically significantly greater for ropinirole (n = 175), compared with placebo (n = 184) at all assessment points beginning at day 3 through to week 12 LOCF (P < 0.001). A statistically significantly greater proportion of patients were classified as responders on the Clinical Global Impression-Improvement scale at all assessment points from day 3 through week 12 LOCF (P < 0.001) and on the Patient Global Improvement scale at all assessment points from day 1 (P = 0.013) through day 7 LOCF (P < or = 0.05 for days 2-7 LOCF) and at week 12 LOCF (P < 0.001). Ropinirole is associated with consistent early and sustained improvements in the symptoms of RLS, as rated by patients and physicians.

Recognition, diagnosis, and treatment of restless legs syndrome

To review the symptoms, diagnosis, and treatment of restless legs syndrome (RLS) and its relevance to nurse practitioners (NPs). Comprehensive review of the scientific literature on the diagnosis and treatment of RLS in adults. RLS is a chronic neurological disorder that, with varying degrees of severity, affects 5%-10% of the general population. Because of the circadian pattern of onset, the symptoms of RLS may be associated with significant sleep disturbance and may have a negative impact on quality of life. RLS is characterized by a compelling urge to move the legs and usually accompanied or caused by uncomfortable sensations in the legs. Symptoms begin or worsen during periods of rest or inactivity and are worse in the evening or at night. Other features supportive of a diagnosis include a family history, the presence of periodic leg movements in sleep, and the relief of symptoms after treatment with a dopaminergic therapy. Although the etiology of RLS is unknown, it is thought that symptoms result from a central dopaminergic dysfunction and dopamine agonists are considered first-line treatment for moderate-to-severe primary RLS. Nondopaminergic therapies and nonpharmacologic interventions may also be appropriate in the management of less severe cases of RLS. NPs are often the first healthcare providers to see patients with RLS and therefore need to be able to accurately recognize and diagnose the disorder; this, in turn, will enable them to successfully manage the treatment of RLS.

The Use of Dopamine Agonist in the Treatment of Restless Legs Syndrome: Caution for Practitioners and Bipolar Patients

The Use of Dopamine Agonist in the Treatment of Restless Legs Syndrome: Caution for Practitioners and Bipolar Patients

Response to ropinirole in restless legs syndrome is independent of baseline serum ferritin

Iron-deficient states can be associated with restless legs syndrome (RLS), and serum ferritin is recommended in screening for iron deficiency in RLS.1 2 Dopamine agonists are first-line treatment for idiopathic...

The Burden of Restless Legs Syndrome

Restless legs syndrome (RLS) affects approximately 10-15% of the general population and has deleterious effects on sleep and subsequent daytime performance. The disorder may also give rise to long-term complications such as psychological distress and diminished quality of life. The condition is often unrecognized or misdiagnosed, and the magnitude of the effects of RLS on the sizeable proportion of undiagnosed (and therefore untreated) individuals has not previously been evaluated. This study examined the impact of RLS on overall health status, sleep, psychological functioning, work productivity, and daily activities in individuals with diagnosed and in those with undiagnosed (self-reported) RLS. An internet-based survey was conducted on a multimillion-member panel of US adults. Eligible participants were currently experiencing RLS symptoms as determined using established diagnostic criteria. Participants provided information related to self-reported RLS diagnosis, treatment, symptom frequency and severity, and responses to validated instruments (Medical Outcomes study [MOS] Short Form 12, version 2 [SF-12v2], MOS Sleep Scale, Center for Epidemiological Studies Depression Scale [CES-D], Work Productivity and Activity Impairment - General Health Questionnaire [WPAI-GH] and Work Limitations Questionnaire [WLQ]). Analysis of co-variance (ANCOVA) models were developed to evaluate the relationships among symptom severity, diagnosis status, age, and sex, and the impact of RLS. Participants included 702 adults with RLS symptoms. Means for the SF-12v2 scores (physical component score = 35.6, mental component score = 42.6) were at least 1 standard deviation lower than sex- and age-adjusted general population norms. Participants reported poorer sleep quality scores across each MOS Sleep Scale domain, with differences from published norms of >16 points on 100-point scales, as well as approximately 1hour less sleep per night on average. A majority (64%) met the cut-off score for depression. Compared with population norms, the sample reported greater limitations in time management, physical demands, mental/interpersonal demands, general work output, and usual activities. Symptom intensity and frequency were shown to be the primary predictors of RLS impact on the various outcomes. These results support previous reports that RLS often goes undiagnosed or misdiagnosed. The results of this survey also suggest that regardless of whether RLS is recognized, the burden of the disorder is substantial, implying a need for improved diagnosis and management of RLS.

Treatment wish of individuals with known and unknown restless legs syndrome in the community

Restless legs syndrome (RLS) is a frequent sleep disorder with a prevalence of 5% to 15% in Caucasian populations. Dopaminergic treatment is known to reduce sensorimotor RLS symptoms and is approved for RLS, but not all patients ask for treatment. About 2% to 3% of patients presenting to a primary care physician require RLS-specific treatment. The overall treatment preference of RLS sufferers, however, is still unknown. The aim of this study was to assess the prevalence and treatment preference in patients with previously diagnosed and those with yet undiagnosed RLS in a population-based survey in Germany. Cross-sectional health survey with face-to-face interviews with 1312 participants in the Dortmund Health Study. RLS was assessed with standardized, validated questions addressing the four minimal diagnostic criteria for RLS defined by the International Restless Legs Syndrome Study Group. Participants were aged 25 to 75 years and were randomly selected from the city register. The overall prevalence of individuals with a known doctor diagnosis of RLS was 2.3%. In addition, 6.5% fulfilled the four minimal criteria but did not know about this diagnosis yielding an overall prevalence of 8.8%. Prevalence was higher in women (10.2%) and German descendents (9.2%) compared to men (7.1%) and migrants (6.7%). Almost 60% of all RLS cases reported symptoms at least once a week. 33.3% of cases with a known RLS diagnosis and 14.1 % with an unknown diagnosis had an RLS treatment wish. The latter is determined by knowledge of the diagnosis, daily symptoms, diabetes and sleep disturbance. About every fourth RLS case knows about the diagnosis and overall every fifth RLS case wishes medication to effectively reduce symptoms, corresponding to 1.6% of the whole study population.

Anticonvulsants to treat idiopathic restless legs syndrome: systematic review

Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. Many treatments have been used to minimize the discomfort of the disease, among them the anticonvulsant therapy. This review aims to evaluate the efficacy and safety of anticonvulsant treatment for idiopathic RLS. Systematic review of randomized or quasi-randomized, double blind trials on anticonvulsant treatment for RLS. relief of RLS symptoms, subjective and objective sleep quality, quality of life, and adverse events associated with the treatments. A total of 231 patients were randomized in three cross over studies and one parallel study. Three studies with carbamazepine, one with sodium valproate, and one with gabapentin, and they were very heterogeneous so we could not perform a meta-analysis. There is no scientific evidence on RLS treatment with anticonvulsants for clinical practice.

MOTHERISK ROUNDS: Medications for Restless Legs Syndrome in Pregnancy

According to epidemiological data, pregnant women have a two or three times higher risk of experiencing restless legs syndrome (RLS) than the general population. Current evidence suggests that dopaminergic dysfunction, impaired iron homeostasis, and genetic predisposition may be involved in the pathophysiology of RLS. Four classes of medications have been used for patients with RLS, but pregnancy elicits a therapeutic concern. Although two dopamine agonists, ropinirole and pramipexole, have been approved by the FDA for the treatment of RLS and are currently the first-line treatment for daily symptoms, there is very little information on the teratogenic risks of these new medications. Therefore, they are not currently recommended for use during pregnancy. Medications with a more extensive safety record in pregnancy include opioids; antiepileptics, such as carbamazepine and gabapentin; and certain benzodiazepines. Ruling out iron deficiency should be an integral part of a treatment plan for RLS in pregnancy. Before management with medication is introduced, every patient should be assessed for iron status with measurement of serum ferritin.

Valvular heart disease associated with taking low-dose pergolide for restless legs syndrome

A 49-year-old female took low-dose pergolide (625 microg daily) for approx. 5 years (approximately cumulative dose 1.140 g/5 years) for the treatment of restless legs syndrome. She developed moderate to severe mitral and aortic valve insufficiency, requiring semi-urgent double-valve replacement. The initial diagnosis of rheumatic valve disease was refuted on histological examination of the valves due to the lack of typical calcification and neovascularization. Valvular heart disease is associated with the use of dopamine agonists for the treatment of Parkinson's disease and obesity, typically at much higher doses.

Effect of Nonergot Dopamine Agonists on Symptoms of Restless Legs Syndrome

We performed a meta-analysis of randomized placebo-controlled trials of nonergot dopamine agonists (NEDAs) for the treatment of restless legs syndrome. A systematic literature search was conducted through July 2007. The primary outcome measures assessed were the percentage of responders to medication as determined by the Clinical Global Impression-Improvement (CGI-I) scale and the adjusted mean change in the International Restless Legs Syndrome Study Group Scale (IRLS) score from baseline compared with placebo. Meta-regression analysis was performed to evaluate the impact of study duration on the primary outcomes. Safety endpoints were also evaluated. A total of 14 trials (n = 3,197 subjects) were included in the meta-analysis. NEDA use resulted in greater response as measured by the CGI-I scale (relative risk [RR] 1.36; 95% CI, 1.24 to 1.49; P <.001), and greater reductions in IRLS scores (weighted mean difference [WMD] -4.93; 95% CI, -6.42 to -3.43; P <.001) from baseline vs placebo. Meta-regression analysis showed an inverse relationship between study duration and reduction in IRLS score. NEDAs were associated with a significant risk of adverse events (including nausea, dizziness, somnolence, and fatigue.) Use of NEDAs in patients with moderate-to-severe restless legs syndrome results in significant reductions in symptom severity, but a significant portion of patients will discontinue their use as a result of adverse events.

Ropinirole treatment for restless legs syndrome

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

Ropinirole treatment for restless legs syndrome

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

Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies

The restless legs syndrome (RLS) is a common sensory-motor disorder of sleep/wake motor regulation with prevalence rates between 3% and 10%. In its more severe forms, RLS is a burdening disorder with disturbed sleep and significantly impaired quality of life. Restless legs symptoms are dramatically relieved with levodopa and dopamine agonists, which are first-line treatment for this disorder. In addition, opioids have been shown to provide a marked symptomatic relief. This unique responsiveness of RLS to both dopaminergic agents and opioids places it at the crossroad of the two systems implicated in the placebo response. Indeed, in recent large-scale studies a substantial placebo response was observed. We performed a meta-analysis to provide an evidence-based estimate of the magnitude of the placebo response in RLS. Search strategies included the electronic databases PubMed and the Cochrane Clinical Trials Registry (from 1966 to March 2007), the reference lists of retrieved articles, hand-searching abstract books of sleep, neurology and movement disorder congresses and visiting clinical trial register web sites. All randomized, double-blind, placebo-controlled studies exploring a pharmacological treatment in subjects with RLS were considered. Outcome measures from five domains were extracted: RLS severity, subjective sleep parameters, sleep parameters derived from nocturnal polysomnography, periodic leg movements during sleep (PLMS) and daytime functioning. We identified 60 clinical trials and 36 of them were eligible for the meta-analysis. In 24 trials, the pooled placebo response rate was 40.09% (95% CI: 31.99-48.19). The placebo effect was large for the primary outcome measure in most studies, which is the International Restless Legs Severity Scale (-1.48, CI: -1.81 to -1.14), notably smaller for other RLS severity scales, moderate for daytime functioning, small to moderate for subjective and objective sleep parameters, very small for PLMS and absent for sleep efficiency. This meta-analysis yields several implications for the planning of both clinical RLS treatment studies and basic research programs.

Association between restless legs syndrome and Chiari type 1 malformation

Chiari type 1 malformations (CM-1) consist of the downward displacement of the cerebellar tonsils out of the inferior opening of the skull and into the spinal canal. In relation to this, a few studies in the literature have drawn attention to the possible role of the upper brainstem, diencephalon, red nucleus, and cerebellum in the pathogenesis of restless legs syndrome (RLS). Herein, we present five cases of RLS who were also found to have CM-1 malformations. The cases were notable for an early onset of RLS and a poor response to dopaminergic treatment. The patients fulfilled the diagnostic criteria for RLS according to the International RLS Study Group. None of the patients had a family history of RLS or any other condition known to be associated to RLS. The patients ranged in age from 20 to 31 years old. Four of the patients indicated occasional pain in the occipital–suboccipital area upon questioning about CM-1-related symptoms. All cases had used at least two different drugs known to be effective in RLS treatment. Our opinion is that CM-1-related involvement of the cerebellum and/or connections of the cerebellum with the basal ganglia may have contributed to the development of RLS in these cases.

Open-label study of the long-term efficacy and safety of pramipexole in patients with Restless Legs Syndrome (extension of the PRELUDE study)

Background and objective To demonstrate the long-term efficacy and safety of pramipexole for Restless Legs Syndrome (RLS) using physician and patient RLS ratings, along with subjective assays of sleep parameters, in a 26-week, open-label trial. Patients and methods Among 107 Finnish adults with moderate to severe RLS, pramipexole initiated at 0.125 mg/day was titrated to a maximum 0.75 mg/day. Efficacy evaluations included the International RLS Study Group Rating Scale (IRLS), Patient Global Impression (PGI) scale, Clinical Global Impressions-Improvement (CGI-I) scale, Epworth Sleepiness Scale (ESS), and Short Form-36 (SF-36) Health Survey. Subjective Sleep Quality was assessed by patient ratings of sleep and morning tiredness. Safety was documented by Adverse Events reported in >5% of patients. Results The mean reduction in IRLS score was 73.5% ( P < 0.05). The IRLS responder rate, defined by score reduction of ⩾50%, was 81.3%. On the PGI scale, 89.7% of patients rated themselves as “very much” or “much” better. By CGI-I assessment, 94.8% of patients were considered either “very much” or “much” improved. Mean ESS score showed a modest but statistically significant reduction ( P < 0.05) within the normal range, indicating that long-term pramipexole did not increase daytime sleepiness. On the SF-36 all 8 domains showed improvement, 5 of them statistically significant ( P < 0.05) and 4 of these 5 (role-physical, bodily pain, vitality, and role-emotional) by >10 points on a 100-point scale. Subjective Sleep Quality also improved. The most frequent Adverse Events were influenza (17.8%), headache (15.0%), and fatigue (10.3%). Conclusion Pramipexole is well tolerated and effective for long-term treatment of RLS.

Clinical experience with pramipexole in the treatment of restless legs syndrome

Pramipexole is a non-ergoline dopamine agonist with a high selectivity for D2 and D3 receptors. Initially approved for Parkinson's disease, it was approved by the FDA and EMEA in 2006 for the treatment of idiopathic restless legs syndrome in adults. A single oral dose of pramipexole of between 0.125 and 0.750 mg, taken 2 – 3 h before bedtime, is usually able to control sensory symptoms and motor signs of restless legs syndrome. In clinical practice, tailoring pramipexole treatment based on demographic and clinical characteristics of patients is recommended. In addition, pramipexole seems to be safe and well tolerated. Augmentation, the most common side effect of levodopa, is less prevalent after treatment with pramipexole. In addition, the recurrence of unpleasant symptoms due to pramipexole is uncommon.

Patterns of treatment for restless legs syndrome in primary care in the United Kingdom

Background: The dopamine agonists pramipexole and ropinirole are licensed for the treatment of moderate to severe idiopathic restless legs syndrome (RLS) in Europe and the United States. In addition, various drugs that are not approved for this indication have been used for symptomatic treatment of RLS, including analgesics, quinine, and anxiolytics.Objective: The purpose of this analysis was to describe patterns of treatment of newly diagnosed RLS, including treatment effectiveness and resource utilization, in primary care in the United Kingdom.Methods: This was a cohort study that employed the UK General Practice Research Database. Two cohorts were assembled, one consisting of patients with an initial diagnosis of RLS between 1990 and 2004 and the other consisting of patients without RLS matched to cases in a 10:1 ratio by general practice, year of birth, sex, and registration with the practice on the case index date (date of the RLS diagnosis). The frequency of RLS-specific symptoms was estimated based on records of prescriptions for sleep medications and antidepressants, and reported cramps and leg problems other than RLS. Rates of resource use in the 2 years before and after the index date were estimated for both cohorts based on the numbers of total prescriptions, referrals to secondary care, and laboratory tests.Results:The RLS cohort comprised 8621 patients and the matched cohort 85,087 patients. Age and sex distributions were comparable between groups. The annual frequency of prescriptions for sleep medications in the RLS cohort increased significantly from 19.8% and 21.6% in the 2 years before the diagnosisof RLS to 27.4% in the first year after the diagnosis and 25.2% in the second year (all comparisons, P < 0.001). A similar pattern was observed for antidepressants in the RLS cohort (23.5%, 26.7%, 31.0%, and 29.6%, respectively; P < 0.001). Prescription rates were nearly constant in the matched cohort. The frequency of cramps and other leg problems was highest in the year before the diagnosis of RLS, declined in the first year after the diagnosis, and increased thereafter. Compared with the matched cohort, rates of prescriptions, referrals, and laboratory tests ranged from 49.7% to 59.0% higher in the RLS cohort in the 2 years before the diagnosis of RLS and from 63.4% to 91.4% higher in the 2 years after the diagnosis (all comparisons, P < 0.001).Conclusion: In patients with newly diagnosed RLS in this UK primary care cohort, use of medications that are not approved for the treatment of RLS was not associated with a reduction in clinical symptoms or health care resource utilization between 1990 and 2004.

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 ⩾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.