Pramipexole for the treatment of restless legs syndrome

Restless legs syndrome (RLS) is a common disorder that is estimated to affect 10% of Americans. However, it remains largely undiagnosed and untreated by clinicians. The primary symptoms of this condition are leg discomfort or an urge to move that is temporarily relieved by movement and is worse at rest and at bedtime. RLS impacts the quality of life of the sufferer by disrupting sleep and disturbing or curtailing work and social activities. Approximately 80% of RLS sufferers also have periodic limb movements during sleep, in which repetitive leg movements fragment sleep and may result in daytime drowsiness. RLS may be treated by dopaminergic agents, benzodiazepines, anticonvulsants and opiates; dopamine agonists are currently considered first-line therapy for this condition. Pramipexole has been studied in the treatment of RLS since 1998. This article reviews the role of this medication in the management of this serious neurological disorder.     

Pramipexole for the treatment of restless legs syndrome

Restless legs syndrome (RLS) is a common disorder that is estimated to affect 10% of Americans. However, it remains largely undiagnosed and untreated by clinicians. The primary symptoms of this condition are leg discomfort or an urge to move that is temporarily relieved by movement and is worse at rest and at bedtime. RLS impacts the quality of life of the sufferer by disrupting sleep and disturbing or curtailing work and social activities. Approximately 80% of RLS sufferers also have periodic limb movements during sleep, in which repetitive leg movements fragment sleep and may result in daytime drowsiness. RLS may be treated by dopaminergic agents, benzodiazepines, anticonvulsants and opiates; dopamine agonists are currently considered first-line therapy for this condition. Pramipexole has been studied in the treatment of RLS since 1998. This article reviews the role of this medication in the management of this serious neurological disorder.     

Pramipexole in restless legs syndrome: an evidence-based review of its effectiveness on clinical outcomes

INTRODUCTION: Restless legs syndrome (RLS) affects 5-15% of adults, but is often unrecognized and consequently misdiagnosed. The International Restless Legs Scale (IRLS) has been developed and validated to assess the severity of RLS. Currently, the most common treatment for RLS is levodopa, but this may lead to augmentation of symptoms. Pramipexole has been developed as an alternative treatment for patients diagnosed with RLS. AIMS: The objective of this article is to review the evidence of the effectiveness of pramipexole for the clinical management of patients with RLS. EVIDENCE REVIEW: There is clear evidence that pramipexole reduces the leg movements associated with RLS, as measured by improvements in both the IRLS and the Clinical Global Impression (CGI) score. There is also moderate evidence that the drug improves sleep quality. Pramipexole clearly improves the anxiety and depression often associated with RLS. Augmentation may be associated with pramipexole treatment, but the evidence is contradictory and augmentation may be more associated with patients pretreated with levodopa or with patients with primary RLS rather than those with secondary RLS. Pramipexole therapy appears to be well tolerated, with only mild-to-moderate adverse events reported. OUTCOMES SUMMARY: Pramipexole reduces leg movements in RLS, and is well tolerated. Further investigation is required to confirm the preliminary evidence that pramipexole restores normal sleep architecture and restores a normal quality of life in patients with RLS. Health economic studies would be valuable in demonstrating the true impact of pramipexole on the social burden of RLS.     

Drug-induced restless legs syndrome

Restless legs syndrome can be very troublesome but it has no serious physical complications. The underlying causes are unknown, but it can be triggered or aggravated by a drug. In early 2010, about 60 cases of drug-induced restless legs syndrome had been published in detail. The drugs implicated were mainly psychotropics, especially antidepressants and neuroleptics. Some drugs used to treat restless legs syndrome, especially dopaminergic drugs, can in fact aggravate symptoms. Drug-induced restless legs syndrome generally resolves when the dose is reduced or the drug is withdrawn. Dysfunction of the dopaminergic system has been implicated in some cases. In practice, when a patient presents with restless legs syndrome, the role of a drug, especially a psychotropic, should be considered. Drug withdrawal or a dose reduction may be beneficial.     

Rotigotine transdermal patch: in restless legs syndrome

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

Pharmacotherapy for restless legs syndrome

Introduction: Restless legs syndrome (RLS) is a common condition characterized by paresthesia and an urge to move. Predominantly, symptoms occur at rest in the evening or at night, and they are alleviated by moving the affected extremity. RLS prevalence in the general population has been estimated to be approximately 5%.

Areas covered: This review presents all options for the treatment of RLS.

Expert opinion: Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS, that is, when symptoms impair the patient's quality of life, daytime functioning, social functioning or sleep. Treatment on demand is a clinical need in some RLS patients, and medications include carbidopa/levodopa, pramipexole, ropinirole, oxycodone, methadone, codeine and tramadol. Chronic RLS should be treated with either a nonergot dopamine agonist or an α-2-δ calcium channel ligand. A dopamine agonist is a more appropriate choice in the presence of depression and overweight. As α-2-δ ligands can alleviate chronic pain and may be helpful in treating anxiety and insomnia, the presence of any of these comorbidities may favor their use. For RLS present through much of the day and night, the use of long-acting agents, such as the rotigotine patch or gabapentin enacarbil should be considered. In refractory RLS, oral prolonged release oxycodone–naloxone should be considered.     

不安腿综合征的药物治疗

不安腿综合征是一种常见的神经系统感觉运动障碍疾病,常伴有睡眠障碍。它可见于任何年龄,因缺乏特异性的实验室辅助诊断依据,大多数患者在发病数年后仍不能被识别,甚至被误诊,更得不到适当治疗。过去的数十年里,多个大型临床研究证实,几种类型的药物可用来改善患者症状,包括多巴胺能药物、抗癫痫药物、鸦片类药物和苯二氮革类药物。     

普拉克索治疗不安腿综合征临床疗效及安全性研究

目的:评价普拉克索治疗原发性不安腿综合征(RLS)的临床疗效和安全性。方法:本研究采用随机平行对照临床试验的研究设计方案,将80例原发性RLS受试者随机分为试验组和对照组,每组各40例。试验组的受试者给予普拉克索治疗,对照组的受试者给予美多巴治疗,共治疗8周。疗效的评定采用国际不安腿综合征评估量表(IRLS),匹兹堡睡眠质量指数(PSQI)和汉密尔顿抑郁量表(HAMD)。同时,密切观察并记录普拉克索治疗的不良反应,评价其安全性。两组受试者分别于治疗前,治疗8周结束后和随访3个月进行疗效评估,以及治疗后评估其安全性。结果:治疗前,两组受试者IRLS,PSQI和HAMD评分比较,差异无统计学意义(P>0.05)。治疗后,两组受试者的IRLS,PSQI和HAMD评分均显著降低,与同组治疗前比较,差异显著,有统计学意义(P<0.01)。治疗后,与对照组比较,试验组原发性RLS受试者的IRLS,PSQI和HAMD评分均显著低于对照组。二者比较,差异有统计学意义(P<0.05)。但两组不良反应比较,差异无统计学意义(P>0.05)。结论:普拉克索不仅能有效缓解原发性不安腿综合征的临床症状,还可以有效改善这些患者的睡眠和焦虑。该药物的不良反应较小,患者可以耐受。     

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.     

Treatment options for restless legs syndrome

Background: Restless legs syndrome (RLS) is a common condition characterized by dysesthesia and an urge to move. Predominantly, symptoms occur at rest in the evening or at night, and they are alleviated by moving the affected extremity or by walking. Although the etiopathogenesis of RLS is still unknown, the rapid and dramatic improvement of RLS with dopaminergic agents suggests that dopaminergic system dysfunction may be a basic mechanism. Dopaminergic agents are the best-studied agents, and are considered first-line treatment of RLS. Objective: To review all options for the treatment of RLS, including the non-pharmacological ones. Methods: The treatment suggestions are based on evidence from studies published in peer-reviewed journals, or upon a comprehensive review of the medical literature. Results/conclusion: Extensive data are available for levodopa and dopamine agonists, especially for pramipexole and ropinirole. Pharmacological treatment should be limited to those patients who suffer from clinically relevant RLS with impaired sleep quality or quality of life. A treatment on demand is a clinical need in RLS cases that present intermittent symptoms.     

Ropinirole treatment for restless legs syndrome

In this paper we discuss therapy with ropinirole (known as adartrel in the United Kingdom) in patients with restless legs syndrome. Restless legs syndrome is characterized by an urge to move the legs, uncomfortable sensations in the legs and worsening of these symptoms during rest with at least temporary relief brought on by activity. Current recommendations suggest dopaminergic therapy (levodopa or dopamine receptor agonists like ropinirole) as the first-line treatment for restless legs syndrome. Based on the results of randomized, placebo-controlled, double-blind trials, we conclude that ropinirole is effective in reducing symptoms of restless legs syndrome in the general population. Ropinirole has no serious or common side effects that would limit its use significantly. Rebound and augmentation problems are relatively rarely seen with ropinirole, although properly designed comparative trials are still needed to address this question. It must be noted, however, that most published studies with ropinirole compare this drug with placebo. Very few studies have compared ropinirole with other drugs (L-dopa, gabapentin, opioids, benzodiazepines, other dopaminergic agents and selegiline hydrochloride). No cost-effectiveness trial has been published yet. Treatment of restless legs syndrome with ropinirole shows it to be effective, well-tolerated and safe and it can be used in restless legs syndrome in general.     

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.     

Emerging drugs for restless legs syndrome

Restless legs syndrome (RLS) is a common, but often underdiagnosed, neurological disorder, which is characterised by an imperative urge to move the extremities associated with paraesthesias, worsening of symptoms at rest and in the evening or at night, and, as a consequence, sleep disturbances. RLS affects 1-10% of the population. The aetiology of RLS is unknown, but besides genetic factors the dopaminergic and opioidergic system may play a crucial role and new developments also point to an exciting iron-dopamine connection in the pathophysiology of this burdening disorder. Due to the limited disease-specific knowledge, current treatment strategies are not curative, but nevertheless may produce an effective and lasting relief of symptoms. Although clinically based treatment has focused on levodopa, opioids and benzodiazepines for a long time, evidence-based and clinical guidelines identify dopamine agonists as a first-line treatment for daily restless legs symptoms. These substances are now in the process of registration for this indication. Ropinirole is the first dopamine agonist that has been approved by the FDA in May 2005. In addition, several promising new therapies with nondopamine profiles are under development for RLS.     

Ropinirole: for the treatment of restless legs syndrome

Ropinirole is a non-ergoline dopamine agonist that exhibits a high affinity for D(2) and D(3) receptors but little or no affinity for D(1)-like and non-dopaminergic receptors. Symptoms of restless legs syndrome (RLS) [measured using the International Restless Legs scale and Clinical Global Impression-Global Improvement Scale scores] significantly improved with ropinirole compared with placebo in large, randomised, double-blind trials. Ropinirole reduced periodic leg movements and improved sleep efficiency relative to baseline and placebo in several trials (two of which were randomised, double-blind and relatively large) in patients with RLS. Ropinirole was generally well tolerated in patients with RLS; adverse events were generally mild to moderate in nature and consistent with those expected of dopamine agonists. Few patients receiving ropinirole withdrew from therapy because of adverse events, the most predominant of which were nausea and headache.     

Current treatment options for restless legs syndrome

Restless legs syndrome (RLS) is a common but often underdiagnosed neurological disorder characterised by an imperative desire to move the extremities associated with paraesthesias, motor restlessness, worsening of symptoms at rest in the evening or at night and, as a consequence, sleep disturbances particulary. Additionally, most patients with RLS have periodic limb movements during sleep and relaxed wakefulness. The aetiology of RLS remains unknown. Treatment of RLS is generally symptomatic, a causal therapy is possible only in the secondary forms. Dopaminergic agents including levodopa and dopamine agonists such as pergolide, pramipexole, cabergoline and ropinirole are regarded as the treatment of choice for idiopathic RLS, however, the development of augmentation of symptoms, especially under levodopa therapy, may be a major problem. Except in special circumstances, opioids and anticonvulsants such as gabapentin or benzodiazepines, are regarded as second-line treatment. In secondary RLS, the underlying illness should first be treated, although dopaminergic drugs may also be helpful.     

不宁腿综合征的研究进展

不宁腿综合征（Restlesslegssyndrome，RLS）是近几年再次引起国内外倍加重视的常见、多发病。由于该征的主要临床表现多集中在小腿深部强烈地异样不适感，休息或夜晚睡眠时加重，活动后暂时缓解，故有“胫骨不安症”、“腿部神经过敏”、“无力性脚感觉异常”、“肌性焦虑”、“夜间阵挛综合征”等诊断名称，１９４５年Ekbom对５０００人调查和１７５例复习总结后提出RLS诊断命名延用至今。但该综合征的多因素性和缺乏专科识别性，往往归因于失眠症、精神紧张、关节炎、神经质或老化性改变。随着病理生理学、分子生物学、药理学和神经…     

Investigational approaches to therapies for restless legs syndrome

Introduction: Restless Legs Syndrome (RLS) is a common neurological disorder that impairs nocturnal rest, causing decreased alertness, depressed mood, reduced job performance and poor quality of life. In patients affected by severe RLS, pharmacological treatment is mandatory.

Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 – 2014. It focuses on drugs currently in development for the treatment of RLS.

Expert opinion: The drugs currently available for treating RLS do not always allow the patient to obtain a dose capable of controlling the symptoms, particularly in the long term. There is still the need for effective and well-tolerated new drugs. Monoamine oxidase B inhibitors could be good candidates for the initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone has demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled with first-line drugs; it could be used as a long-term treatment option in severe cases of RLS for which alternative satisfactory drug regimens are unavailable. There is a paucity of data comparing medications in head-to-head trials to determine their relative effectiveness and adverse event profiles. Furthermore, there is also a need for further studies that evaluate nondopaminergic agonists and combination therapies for treating RLS.