A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) in conjunction with the European Restless Legs Syndrome Study Group (EURLSSG) and the RLS Foundation (RLS-F) to develop evidence-based and consensus-based recommendations for the prevention and treatment of long-term pharmacologic treatment of dopaminergic-induced augmentation in restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force made the following prevention and treatment recommendations: As a means to prevent augmentation, medications such as α2δ ligands may be considered for initial RLS/WED treatment; these drugs are effective and have little risk of augmentation. Alternatively, if dopaminergic drugs are elected as initial treatment, then the daily dose should be as low as possible and not exceed that recommended for RLS/WED treatment. However, the physician should be aware that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment by either medication should start only when symptoms have a significant impact on quality of life in terms of frequency and severity; intermittent treatment might be considered in intermediate cases. Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough night-time symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation the patient can be switched either to an α2δ ligand or rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In more severe cases of augmentation an opioid may be considered, bypassing α2δ ligands and rotigotine.

A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) to develop evidence-based and consensus-based recommendations for the long-term pharmacologic treatment of restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force reviewed the results of all studies of RLS/WED treatments with durations of 6 months or longer presented at meetings over the past 2 years, posted on Web sites of pharmaceutical companies, or published in peer-reviewed journals, asking the questions, "What is the efficacy of this treatment in patients with RLS/WED?" and "What is the safety of this treatment in patients with RLS/WED?" The Task Force developed guidelines based on their review of 61 papers meeting inclusion criteria, and using a modified evidence-grading scheme. Pregabalin has been established as effective for up to 1 year in treating RLS/WED (Level A evidence). Pramipexole, ropinirole, and rotigotine have been established as effective for up to 6 months in treating RLS/WED (Level A). The following drugs have been established as probably effective (Level B) in treating RLS/WED for durations ranging from 1 to 5 years: gabapentin enacarbil, pramipexole, and ropinirole (1 year); levodopa (2 years); and rotigotine (5 years). Because of associated safety concerns, pergolide and cabergoline should not be used in the treatment of RLS/WED unless the benefits clearly outweigh the risks. Other pharmacologic therapies have insufficient evidence to support their long-term use in treating RLS/WED. The IRLSSG Task Force also developed consensus-based strategies for the prevention and treatment of complications (such as augmentation, loss of efficacy, excessive daytime sleepiness, and impulse control disorders) that may develop with the long-term pharmacologic treatment of RLS/WED. The use of either a dopamine-receptor agonist or α2δ calcium-channel ligand is recommended as the first-line treatment of RLS/WED for most patients, with the choice of agent dependent on the patient's severity of RLS/WED symptoms, cognitive status, history, and comorbid conditions.

Background: Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis‐Ekbom disease), there have been major therapeutic advances in the field. Furthermore, the management of RLS is now a part of routine neurological practice in Europe. New drugs have also become available, and further randomized controlled trials have been undertaken. These guidelines were undertaken by the EFNS in collaboration with the European Neurological Society and the European Sleep Research Society.Objectives: To provide an evidence‐based update of new treatments published since 2005 for the management of RLS.Methods: First, we determined what the objectives of management of primary and secondary RLS should be. We developed the search strategy and conducted a review of the scientific literature up to 31 December 2011 (print and electronic publications) for the drug classes and interventions employed in RLS treatment. Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations made according to the 2004 EFNS criteria for rating.Recommendations: Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short‐term treatment for RLS. However, for the long‐termtreatment for RLS, rotigotine is considered effective, gabapentin enacarbil is probably effective, and ropinirole, pramipexole and gabapentin are considered possibly effective. Cabergoline has according to our criteria a level A recommendation, but the taskforce cannot recommend this drug because of its serious adverse events.

Objectives: To assess the therapeutic efficacy, required dose, and tolerability of pregabalin in patients with idiopathic restless legs syndrome (RLS). Methods: This was a double-blind, placebo-controlled trial with polysomnographic control, providing Class II evidence. Ninety-eight patients underwent a 2-week single-blind period with placebo; 58 were randomized to receive pregabalin or placebo for 12 weeks under a flexible-dose schedule. Endpoints were mean change from baseline in the International Restless Legs Scale (IRLS) total score, Clinical Global Impression (CGI), and RLS-6 scales, as well as changes in periodic limb movements (PLMs) and sleep architecture. Results: Patients under treatment with pregabalin had a greater improvement in IRLS score than under placebo (63% vs 38.2%; p < 0.05). The mean effective dose of pregabalin at the end of treatment was 322.50 mg/day (±98.77), although therapeutic effects were already seen at a mean dose of 139 mg/day. Similarly, improvements were observed on the CGI, RLS-6 scale, and the Medical Outcomes Study sleep scale (all p < 0.01) when compared to placebo. Treatment with pregabalin also resulted in a reduction of the mean (±SD) PLM index (p < 0.001). Furthermore, there was a marked improvement in sleep architecture with an increase in slow wave sleep (p < 0.01), and decreases in wake after sleep onset and stages 1 and 2 (p < 0.05). Pregabalin was generally well-tolerated. Adverse events were mild but common, and included unsteadiness, daytime sleepiness, and headache. Conclusions: This study shows significant therapeutic effects of pregabalin on both sensorial and motor symptoms in restless legs syndrome. Treatment with pregabalin was associated with an improvement of sleep architecture and periodic limb movements. Adverse events included unsteadiness and sleepiness and should be screened carefully in the working population, particularly when pregabalin is administered in the afternoon. Classification of evidence: This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.