Restless Legs Syndrome (Restless Legs)

A disorder characterized by aching or burning sensations in the lower and rarely the upper extremities that occur prior to sleep or may awaken the patient from sleep. Complying with an irresistible urge to move the affected limbs brings temporary relief. Sleep may become disrupted, resulting in excessive daytime hypersomnolence. This condition may be associated with UREMIA; DIABETES MELLITUS; and rheumatoid arthritis. Restless Legs Syndrome differs from NOCTURNAL MYOCLONUS SYNDROME in that in the latter condition the individual does not report adverse sensory stimuli and it is primarily a sleep-associated movement disorder. (Adams et al., Principles of Neurology, 6th ed, p387; Schweiz Rundsch Med Prax 1997 Apr 30;86(18):732-736)

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Networked: 1004 relevant articles (109 outcomes, 203 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Parkinson Disease (Parkinson's Disease)
2.	Pain (Aches)
3.	Restless Legs Syndrome (Restless Legs)
4.	Sleep Initiation and Maintenance Disorders (Insomnia)
5.	Schizophrenia (Dementia Praecox)

Experts

1.	Allen, Richard P: 40 articles (03/2015 - 11/2002)
2.	Trenkwalder, Claudia: 37 articles (04/2014 - 01/2002)
3.	Earley, Christopher J: 30 articles (01/2015 - 05/2004)
4.	Kohnen, Ralf: 24 articles (01/2015 - 10/2003)
5.	Högl, Birgit: 22 articles (09/2015 - 08/2005)
6.	Ferini-Strambi, Luigi: 22 articles (03/2015 - 11/2003)
7.	Stiasny-Kolster, Karin: 22 articles (08/2014 - 01/2004)
8.	Garcia-Borreguero, Diego: 17 articles (01/2016 - 06/2004)
9.	Oertel, Wolfgang H: 17 articles (08/2014 - 01/2004)
10.	Walters, Arthur S: 17 articles (12/2013 - 07/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Restless Legs Syndrome:

1.	Dopamine Agonists (Dopamine Agonist)IBA 07/19/2011 - "Review: Dopamine agonists are effective for the restless legs syndrome but may be discontinued due to adverse events." 08/01/2011 - "Safety and efficacy of non-ergot dopamine agonists for the treatment of idiopathic restless legs syndrome have been shown in short-term trials. " 09/01/2004 - "Controlled clinical trials robustly demonstrate the short-term efficacy of dopamine agonists (DA) for restless legs syndrome (RLS), but little is known about the long-term efficacy and long-term adverse events. " 01/01/2013 - "In the last few years, dopamine agonists (DA) have been used as first-line treatment for restless legs syndrome (RLS), a disabling sensorimotor disorder. " 01/01/2011 - "According to clinical guidelines, dopamine agonists are the first-line treatment of restless legs syndrome (RLS). "
2.	pramipexol (pramipexole)FDA LinkGeneric 01/01/2010 - "Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p=0.0005), a significant improvement in both Patient Global Impression (PGI; p<0.0001) and Clinical Global Impressions (CGI-I; p=0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p=0.0016), when compared with those of placebo group at week 6. Pramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder." 01/01/2012 - "Of 287 patients in the full analysis set, the pramipexole group showed significant improvement compared with the placebo group in the change of their International Restless Legs Syndrome Study Group Rating Scale of Severity (IRLS) total score from baseline to week 6 after adjustment of centers and baseline characters (-15.87±0.66 vs. -11.35±0.92, p<0.0001) and in the proportion of patients who were "much improved" and "very much improved" when measured by Clinical Global Impressions-Improvement (81.9% vs. 54.3%, p<0.0001). " 04/01/2011 - "Pramipexole is an effective treatment for restless legs syndrome (RLS), but no controlled studies have lasted >12 weeks. " 01/20/2007 - "Fifty-one patients suffering from idiopathic restless legs syndrome underwent monotherapy with pramipexole in daily doses of 0.25 to 1.0 mg. Therapeutic efficacy was evaluated using three tools, i.e. " 07/15/2010 - "A phase III, open-label, long-term clinical study was performed to evaluate the safety and efficacy of pramipexole in a cohort of 141 Japanese patients with primary restless legs syndrome (RLS). "
3.	IronIBA 11/01/2010 - "The objective of the study was to investigate the frequency and severity of iron depletion in regular blood donors and whether IV iron is more effective than oral to avoid iron depletion and symptoms thereof, especially restless legs syndrome (RLS). " 05/01/2010 - "Finding a safe and effective intravenous iron treatment for restless legs syndrome." 09/01/2015 - "Efficacy of the low-dose Saccharum iron treatment of idiopathic restless legs syndrome." 10/15/2012 - "Intravenous iron given prior to pregnancy for restless legs syndrome is associated with remission of symptoms." 04/01/2012 - "We conducted a retrospective chart review of children with restless legs syndrome (RLS) to evaluate the efficacy of oral iron treatment, which was administered open-label during the course of clinical care. "
4.	Levodopa (L Dopa)FDA LinkGeneric 11/01/2007 - "Levodopa is effective in the treatment of restless legs syndrome (RLS). " 01/01/2007 - "The impressive relief from restless legs syndrome (RLS) symptoms provided by levodopa treatment indicates RLS is caused by a dopaminergic abnormality. " 02/01/2010 - "The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. " 02/01/2010 - "Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study." 12/15/1999 - "Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial."
5.	ropinirole (Requip)FDA LinkGeneric 09/01/2006 - "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. " 10/01/2006 - "Ropinirole is effective in the long-term management of restless legs syndrome: a randomized controlled trial." 12/01/2004 - "Ropinirole is effective in the treatment of restless legs syndrome. " 10/01/2006 - "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. " 08/01/2004 - "Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS). "
6.	N 0437FDA Link 07/01/2008 - "Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial." 03/01/2008 - "Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe." 07/01/2008 - "Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome. " 01/01/2016 - "Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study." 04/01/2015 - "The aim of this study was to summarize the efficacy and tolerability of rotigotine in the treatment of primary restless legs syndrome (RLS). "
7.	Dopamine Agents (Dopaminergic Agents)IBA 01/01/2007 - "Dopaminergic agents are the best-studied agents and are considered first-line treatment of restless legs syndrome (RLS). " 09/01/2001 - "Dopaminergic agents are highly effective in treating restless legs syndrome, but side effects can be problematic. " 02/01/2012 - "Dopaminergic drugs are the mainstay of treatment for restless legs syndrome (RLS). " 12/01/2010 - "Numerous randomised controlled trials have proved the efficacy of dopaminergic and non-dopaminergic drugs in the treatment of restless legs syndrome (RLS). " 10/01/2010 - "Dopaminergic agents are the first-line treatment of restless legs syndrome (RLS), and have been used for the treatment of this disorder since the 1980s. "
8.	1- (((alpha- isobutanoyloxyethoxy)carbonyl)aminomethyl)- 1- cyclohexaneacetic acidIBA 12/01/2012 - "In the 12-week Patient Improvements in Vital Outcomes following Treatment (PIVOT) RLS I and II trials in adult patients with moderate to severe primary RLS (n > 500 total evaluable), once-daily gabapentin enacarbil 600 or 1,200 mg significantly improved mean International Restless Legs Scale (IRLS) total scores compared with placebo, with significantly higher investigator-rated Clinical Global Impression-Improvement (CGI-I) responder rates in gabapentin enacarbil groups than in placebo groups. " 11/01/2009 - "Gabapentin enacarbil at 1200 mg significantly improved restless legs syndrome symptoms compared with placebo. " 02/03/2009 - "XP13512 1,200 mg, taken once daily, significantly improved restless legs syndrome (RLS) symptoms compared with placebo and was generally well tolerated in adults with moderate to severe primary RLS." 12/01/2011 - "Gabapentin enacarbil is a new treatment for restless legs syndrome (RLS). " 01/01/2011 - "This open-label, multicenter, 52-week extension study (NCT00333359) assessed the long-term safety and efficacy of gabapentin enacarbil in subjects with moderate-to-severe primary restless legs syndrome (RLS). "
9.	Opioid Analgesics (Opioids)IBA 12/01/2013 - "Opioids are a potential new treatment for severe restless legs syndrome. " 04/01/2005 - "Opioids have been shown to provide symptomatic relief from dysaesthesias and motor symptoms in restless legs syndrome (RLS). " 07/01/2002 - "Therapeutic studies of the opioids in restless legs syndrome (RLS) are reviewed. " 12/01/2013 - "Opioids can be used to treat patients with severe restless legs syndrome who have had no benefit with first-line drugs. " 12/01/2013 - "Opioids and restless legs syndrome."
10.	Pergolide (Permax)FDA Link 09/15/1998 - "Thus, although pergolide at the dose of 0.25 mg at bedtime provided subjective improvement in symptoms of restless legs and quality of sleep, and objectively decreased leg movements during the first hour in bed, objectively sleep continued to be disrupted. " 04/27/2004 - "To evaluate the short- and long-term safety and efficacy of pergolide therapy for restless legs syndrome (RLS) in a double-blind, placebo-controlled, randomized trial (Pergolide European Australian RLS [PEARLS] study). " 04/27/2004 - "Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS Study." 12/01/1998 - "To assess the efficacy of pergolide in the treatment of restless legs syndrome (RLS). " 05/22/2001 - "An open follow-up of a controlled study in patients with restless legs syndrome (RLS) shows that the beneficial effect of pergolide on RLS symptoms persists throughout at least 1 year. "

Therapies and Procedures

1.	Transdermal Patch 08/01/2011 - "Rotigotine transdermal patch is generally well tolerated after 1 year and provides sustained efficacy for patients with moderate-to-severe restless legs syndrome at a stable dose for up to 5 years. " 08/01/2011 - "We did a prospective open-label extension of a 6-week, double-blind randomised trial to assess the safety, tolerability, and efficacy of rotigotine transdermal patch for up to 5 years in patients with restless legs syndrome. " 08/01/2011 - "Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study." 01/01/2013 - "Safety and efficacy of rotigotine transdermal patch in patients with restless legs syndrome: a post-hoc analysis of patients taking 1 - 3 mg/24 h for up to 5 years." 10/01/2010 - "To assess the efficacy of rotigotine transdermal patch in subjects with moderate to severe idiopathic restless legs syndrome (RLS) and periodic limb movement (PLM) in sleep in a double-blind, randomized, placebo-controlled, multicenter study (NCT00275236). "
2.	Renal Dialysis (Hemodialysis) 03/01/2008 - "Intradialytic aerobic exercise training ameliorates symptoms of restless legs syndrome and improves functional capacity in patients on hemodialysis: a pilot study." 03/01/2008 - "We present the first study on the influence of exercise training on restless legs syndrome (RLS) in patients on hemodialysis (HD). " 02/01/2007 - "A cross-sectional multicentric study in which 166 consecutive hemodialysis patients were evaluated using a standard questionnaire based on diagnostic criteria elaborated by the International Restless Legs Syndrome Study Group was performed. " 03/01/2003 - "Restless legs syndrome in hemodialysis patients in India: a case controlled study." 09/01/2015 - "Uremic restless legs syndrome (RLS) has been related to an enhanced mortality of hemodialysis (HD) patients. "
3.	Deep Brain Stimulation 10/01/2012 - "Globus pallidus deep brain stimulation for refractory idiopathic restless legs syndrome." 08/01/2006 - "We report on 6 advanced Parkinson's disease (PD) patients who underwent bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery whose restless legs syndrome (RLS) improved postoperatively. " 05/01/2015 - "Studies investigating the effects of subthalamic deep-brain stimulation (DBS-STN) on restless legs syndrome (RLS) in Parkinson's disease (PD) are limited and report conflicting results, with some describing the emergence of RLS after DBS-STN, while others report postoperative improvement of this disorder. " 03/01/2006 - "VIM deep brain stimulation does not improve pre-existing restless legs syndrome in patients with essential tremor." 04/01/2005 - "Deep brain stimulation of the GPi treats restless legs syndrome associated with dystonia."
4.	Aftercare (After-Treatment) 11/01/2011 - "The primary outcome measure, change in score on the International Restless Legs Syndrome Scale, showed a statistically significant improvement in RLS during the first 4 weeks after treatment. " 06/01/2015 - "Scores on the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale and ALFF values were measured before and after treatment. " 03/01/2015 - "Neurocognitive function in patients with idiopathic Restless Legs Syndrome before and after treatment with dopamine-agonist." 01/01/2011 - "To compare heart rate variability (HRV) changes in patients with restless legs syndrome (RLS) and in healthy subjects, and to evaluate HRV before and after treatment with pramipexole in RLS patients. " 02/15/2007 - "Restless legs syndrome (RLS) augmentation, defined as a kind of suppression of the circadian rhythm of the disease in which sensory and motor symptoms appear earlier during the day (and over previously unaffected body parts), with a progressive phase advance until, backwards, the symptoms may cover the entire day, has been described only after treatment with dopaminergic drugs. "
5.	Kidney Transplantation 01/01/2015 - "Impact of kidney transplantation on restless legs syndrome." 01/01/2015 - "Refractory restless legs syndrome remitting after dual kidney transplantation." 05/01/2007 - "Evaluation of effect of renal transplantation in treatment of restless legs syndrome." 02/01/2005 - "Restless Legs Syndrome in patients after renal transplantation." 09/01/2002 - "Long-term course of restless legs syndrome in dialysis patients after kidney transplantation."