Prevalence of restless legs syndrome among men aged 18 to 64 years: an association with somatic disease and neuropsychiatric symptoms. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomised, placebo controlled study in 10 European countries. Lisuride treatment of Restless Legs Syndrome: first studies with monotherapy in de novo patients and in combination with levodopa in advanced disease Sex and the risk of restless legs syndrome in the general population. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States. Randomized trial of pramipexole for patients with restless legs syndrome (RLS) and RLS-related impairment of mood. Effect of pramipexole on RLS symptoms and sleep: a randomized, double-blind, placebo-controlled trial. 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Longterm follow up on pergolide Efficacy of cabergoline in restless legs syndrome Ropinirole is effective in the long-term management of restless legs syndrome: a randomized controlled trial. Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS Effective cabergoline treatment in idiopathic restless legs syndrome Controlled withdrawal of pramipexole after 6 months of open-label treatment in patients with restless legs syndrome. A randomized controlled study of pergolide in patients with restless legs syndrome Treatment of restless legs syndrome with gabapentin: A double-blind, cross-over study Ropinirole for restless legs syndrome
St and ardized diagnostic criteria determined by the International Restless Legs Syndrome Study Group were used to investigate the current prevalence of restless legs syndrome ( RLS ) . Possible associations between RLS and neuropsychiatric and somatic complaints were also investigated . A r and om sample of 4,000 men living in central Sweden were sent a question naire that included questions about sleep habits , symptoms of sleepiness , and somatic and neuropsychiatric complaints . Four symptom questions accepted as minimal diagnostic criteria for RLS were also included . Odds ( OR ) ratios and 95 % confidence interval ( CI ) for different variables were calculated by means of multivariate logistic regression ; 5.8 % of the men suffered from RLS . The prevalence of RLS increased with age . Sleep-related complaints were more frequent among the RLS sufferers . Complaints of headache at awakening and daytime headache were reported three to five times more frequently among RLS sufferers and there was a tendency toward reported social isolation related to RLS . Subjects with RLS more frequently reported depressed mood ( OR , 2.6 ; 95 % CI , 1.8 - 3.8 ) , and complained more often of reduced libido ( OR , 2.2 ; 95 % CI , 1.4 - 3.3 ) . RLS sufferers more frequently reported hypertension ( OR , 1.5 ; 95 % CI , 0.9 - 2.4 ) and heart problems ( OR , 2.5 ; 95 % CI , 1.4 - 4.3 ) . Results show that restless legs syndrome is common among men . It is hypothesized that RLS may be associated with several somatic and neuropsychiatric symptoms OBJECTIVE To assess the efficacy , safety , and tolerability of ropinirole in the treatment of patients with restless legs syndrome . METHODS A 12 week , prospect i ve , double blind , r and omised comparison involving 284 patients from 10 European countries . All participants had a score of > or = 15 on the international restless legs scale ( IRLS ) . Patients were r and omised ( 1:1 ) to receive either ropinirole 0.25 - 4.0 mg once daily or placebo . The primary efficacy end point was mean change from baseline to week 12 in total IRLS score . Global improvements ( clinical global impression ( CGI ) scale ) and improvements in sleep , health related quality of life ( QoL ; using generic and disease specific measures ) , work , and other activities were also assessed . RESULTS 112/146 patients ( 76.7 % ) taking ropinirole and 109/138 ( 79.0 % ) taking placebo completed the study . Improvement in IRLS at week 12 with ropinirole ( mean ( SD ) dose , 1.90 ( 1.13 ) mg/day ) was greater than with placebo ( mean ( SE ) : -11.04 ( 0.719 ) v -8.03 ( 0.738 ) points ; adjusted difference = -3.01 ( 95 % confidence interval ( CI ) , -5.03 to -0.99 ) ; p = 0.0036 ) . More patients in the ropinirole group ( 53.4 % ) showed improvement on the CGI scale at week 12 than in the placebo group ( 40.9 % ; adjusted odds ratio = 1.7 ( 1.02 to 2.69 ) ; p = 0.0416 ) . Significant differences on both IRLS and CGI scales favouring ropinirole were apparent by week 1 . Ropinirole was also associated with significantly greater improvements in sleep and QoL end points . The most common adverse events were nausea and headache . CONCLUSIONS Ropinirole improves restless legs syndrome compared with placebo , with benefits apparent by week 1 . It is generally well tolerated Summary .In two 4-week polysomnography pilot studies with 10 patients each , we investigated the efficacy of oral lisuride as monotherapy in de novo RLS patients as well as in combination with levodopa in advanced RLS . Daily doses at study end were 0.3 mg lisuride , plus 150 mg levodopa in the combination study . Marked improvements occurred in both studies in different PLM indexes and in the CGI . Levodopa dose could be decreased by 27 % . Lisuride might be an efficacious treatment for RLS in general , and in combination with levodopa in advanced stage BACKGROUND Restless legs syndrome ( RLS ) is characterized by the desire to move the limbs associated with paresthesias of the legs , a motor restlessness , an intensification of symptoms at rest with relief by activity , and a worsening of symptoms in the evening or at night . Population -based studies are rare , and risk factors in the general population are not known . METHODS Cross-sectional survey with face-to-face interviews and physical examination among 4310 participants in the Study of Health in Pomerania in northeastern Germany . Participants were aged 20 to 79 years and were r and omly selected from population registers .  Restless legs syndrome was assessed with st and ardized , vali date d questions addressing the 4 minimal criteria for RLS as defined by the International Restless Legs Syndrome Study Group . RESULTS The overall prevalence of RLS was 10.6 % , increasing with age , and women were twice as often affected as men . While nulliparous women had prevalences similar to those among men up to age 64 years , the risk of RLS increased gradually for women with 1 child ( odds ratio , 1.98 ; 95 % confidence interval , 1.25 - 3.13 ) , 2 children ( odds ratio , 3.04 ; 95 % confidence interval , 2.11 - 4.40 ) , and 3 or more children ( odds ratio , 3.57 ; 95 % confidence interval , 2.30 - 5.55 ) . Subjects with RLS had significantly lower quality -of-life scores than those without the syndrome . CONCLUSIONS Restless legs syndrome is a common disease in the general population , affecting women more often than men . It is associated with reduced quality of life in cross-sectional analysis . Parity is a major factor in explaining the sex difference and may guide further clarification of the etiology of the disease In a double-blind r and omized crossover trial , oxycodone or placebo was given in divided night-time doses to 11 patients with idiopathic restless legs syndrome ( RLS ) for 2 weeks prior to appropriate polysomnographic studies . Under double-blinded conditions , patients were asked to do daily ratings of their leg sensations , motor restlessness and daytime alertness on a 1 - 4 scale for the 2 weeks prior to the polysomnographic studies and for the nights of the polysomnographic studies as well . Leg sensations ( p < 0.009 ) , motor restlessness ( p < 0.006 ) and daytime alertness ( p < 0.03 ) were significantly improved on oxycodone as compared to baseline or placebo . Patients were studied polysomnographically under double-blinded conditions for 2 nights in each phase of the protocol . On an average dose of 15.9 mg oxycodone ( equivalent to approximately three 5-mg tablets of commercial preparation ) , there was a statistically significant reduction in the number of periodic limb movements in sleep [ (PLMS)/hour sleep ( p < 0.004 ) ] and in the number of arousals/hour sleep ( p < 0.009 ) on drugs as compared to baseline or placebo . A statistically significant improvement was also noted in sleep efficiency ( p < 0.006 ) and 10 of the 11 patients preferred oxycodone over placebo . We conclude that oxycodone is an effective treatment for RLS and PLMS This r and omized , double-blinded , placebo-controlled trial ( NCT00135993 ) assessed efficacy and safety of the dopamine agonist rotigotine in the treatment of idiopathic restless legs syndrome ( RLS ) over a 6-month maintenance period . A total of 505 eligible participants with moderate to severe RLS ( IRLS sum score > or= 15 ) were r and omly assigned to five groups to receive either placebo or rotigotine ( 0.5 , 1 , 2 , or 3 mg/24 hr ) delivered by once-daily transdermal patch ( fixed-dose regimen ) . The two co- primary efficacy parameters decreased from baseline to end of maintenance in IRLS sum score and in clinical global impressions ( CGI-1 ) score . On both primary measures , 2 and 3 mg/24 hr rotigotine was superior to placebo ( P < 0.001 ) . Adjusted treatment differences to placebo for the IRLS sum score were -4.5 ( 95 % CI : -6.9 , -2.2 ) for 2 mg/24 hr rotigotine , -5.2 ( 95 % CI : -7.5 , -2.9 ) for 3 mg/24 hr rotigotine , and for CGI item 1 -0.65 ( 95 % CI : -1.0 , -0.3 ) and -0.9 ( 95 % CI : -1.3 , -0.5 ) for the 2 and 3 mg/24 hr doses , respectively . Skin reactions ( 27 % ) and known dopaminergic side effects such as nausea ( 18.1 % ) and headache ( 11.6 % ) were mostly mild or moderate in rotigotine subjects . Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms . Treatment efficacy was maintained throughout the 6-month double-blind period OBJECTIVES Patients with restless legs syndrome ( RLS ) have an elevated prevalence of mood disorders compared with the general population . We investigated the change of RLS-related mood impairment during treatment of RLS with pramipexole , a dopamine D(3)/D(2 ) agonist . METHODS Adults with moderate to very severe RLS were enrolled in a 12-week , double-blind , placebo-controlled Phase IV pramipexole trial . A moderate to very severe RLS-related mood disturbance at baseline ( score ≥2 on Item 10 of the International RLS Study Group Rating Scale [ IRLS ] ) was also required . Pramipexole ( 0.125 to 0.75 mg once daily ) was flexibly titrated over the first 4 weeks . RESULTS The intent-to-treat population comprised 199 patients on placebo and 203 on pramipexole . At week 12 , adjusted mean total-score changes on IRLS were -14.2±0.7 for pramipexole and -8.1±0.7 for placebo ( p<0.0001 ) , and on the Beck Depression Inventory version II , -7.3±0.4 for pramipexole and -5.8±0.5 for placebo ( p=0.0199 ) . For IRLS item 10 , the 12-week responder rate ( reduction to no or mild mood disturbance ) was 75.9 % for pramipexole and 57.3 % for placebo ( p<0.0001 ) . Study withdrawal rates were higher for placebo ( 20.5 % ) than for pramipexole ( 12.8 % ) . CONCLUSIONS In patients with RLS-related mood  disturbance , pramipexole improved RLS while also improving RLS-related mood impairment .  Tolerability of pramipexole was similar to that in previous studies BACKGROUND Patients with Restless Legs Syndrome ( RLS ) often seek treatment because of sleep problems related to nocturnal symptoms . Our goal was to test the ability of pramipexole to improve sleep in RLS patients and to reconfirm its efficacy for primary RLS symptoms . METHODS Adults with moderate or severe RLS were r and omized to receive placebo or pramipexole ( flexibly titrated from 0.25 to 0.75 mg ) , 2 - 3h before bedtime for 12 weeks . The co- primary outcome measures were change in Medical Outcomes Study ( MOS ) sleep disturbance score and International RLS Study Group Rating Scale ( IRLS ) score at 12 weeks . RESULTS The intent-to-treat population included 357 patients : 178 received pramipexole and 179 received placebo .  At 12 weeks , the adjusted mean change from baseline was greater for pramipexole ( vs. placebo ) for IRLS score ( -13.4+/-0.7 vs. -9.6+/-0.7 ) and MOS sleep disturbance score ( -25.3+/-1.5 vs. -16.8+/-1.5 ) ( p < or=0.0001 ; ANCOVA ) . Responder rates ( clinical and patient global impression and IRLS ) were also significantly higher in the pramipexole group . RLS-QOL score was improved over placebo at Week 12 ( p<0.01 ) as were MOS sleep adequacy ( p=0.0008 ) and quantity ( p=0.08 ) scores . Nine percent of patients in each group withdrew because of adverse events . CONCLUSIONS Pramipexole is effective and well-tolerated for RLS and related sleep disturbance STUDY OBJECTIVES 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 ) . DESIGN Double-blinded , placebo-controlled , parallel-group study . SETTING 15 tertiary referral centers in the USA . PARTICIPANTS 65 patients with RLS and PLMS . INTERVENTIONS Ropinirole ( 0.25 - 4.0 mg per day ) or placebo for 12 weeks . MEASUREMENTS AND RESULTS Data from 59 patients were included in the primary endpoint analysis . PLMS per hour decreased more with ropinirole ( 48.5 to 11.8 ) , compared with placebo ( 35.7 to 34.2 ; adjusted treatment difference : -27.2 ; 95 % confidence interval [ CI ] : -39.1 , -15.4 ; P < .0001 ) . Periodic limb movements with arousal per hour decreased from 7.0 to 2.5 with ropinirole but increased from 4.2 to 6.0 with placebo ( adjusted treatment difference : -4.3 , 95 % CI : -7.6 , -1.1 ; P = .0096 ) . Periodic limb movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but increased from 46.6 to 56.1 with placebo ( adjusted treatment difference : -39.5 ; 95 % CI : -56.9 , -22.1 ; P < .0001 ) . Ropinirole treatment significantly improved patients ' ability to initiate sleep ( P < .05 ) and the amount of Stage 2 sleep compared with placebo ( P < .001 ) . There were also non-significant trends toward increases in total sleep time and sleep efficiency . Sleep adequacy ( measured on the subjective Medical Outcomes Study sleep scale ) was significantly improved with ropinirole treatment ( adjusted treatment difference : 12.1 ; 95 % CI : 1.1 , 23.1 ; P = .0316 ) . In contrast , the placebo group showed a greater increase in Stage 3/4 sleep ( P < .01 ) . No serious adverse events occurred in either group . CONCLUSIONS Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS BACKGROUND AND PURPOSE Restless legs syndrome ( RLS ) patients suffer from symptoms not only at bedtime but also with variable circadian patterns . Transdermal application forms of dopamine agonists are expected to lead to a stable plasma concentration of the active drug which could ease treatment for RLS patients with daytime symptoms and avoid side effects of oral dopaminergic therapies . PATIENTS AND METHODS In this controlled pilot study , 10 patients ( six females , four males , mean age 58 years ) with severe and long-lasting idiopathic RLS were treated during an initial open-label phase for 2 weeks either with one ( n=3 patients ) or , if required , two patches of lisuride every other day ( dose per patch : 3 mg lisuride , nominal effective release rate 7.0 microg lisuride/h ) . Patients were then r and omized to double-blind treatment with lisuride ( n=5 ) or placebo ( n=4 ) for 1 week . RESULTS Severity of RLS clearly improved during open-label and double-blind treatment with lisuride but became worse under placebo according to the International Restless Legs Syndrome Study Group Rating Scale ( IRLS ) , RLS-6 , and Clinical Global Impressions ( CGIs ) scales , and actigraphy assessment s ( periodic leg movement index ) in the 1-week double-blind period . CONCLUSION The explorative findings of this small controlled study suggest that lisuride patches might be an efficacious treatment for RLS patients without clinical ly relevant tolerability problems A double‐blind r and omized crossover study of 7.5 mg bromocriptine at bedtime versus placebo was conducted in 30‐day phases ( with a 2‐week washout period between phases ) in 6 patients with idiopathic restless legs syndrome . Five patients experienced partial subjective improvement in restlessness and paresthesias on bromocriptine as opposed to placebo and expressed a desire to continue on the medication . On bromocriptine , the patients showed polysomnographically a mean Decemberrease of 43 % from control and a mean Decemberrease of 57 % from placebo in the number of periodic movements of sleep per hour of sleep ( p < 0.025 ) . Two of 3 patients with abnormally Decemberreased total sleep time and sleep efficiency showed an improvement in these measures on therapy . The dopamine agonist bromocriptine may be a useful therapy in some patients with restless legs syndrome BACKGROUND AND PURPOSE Restless legs syndrome ( RLS ) is a condition characterized by an urge to move the legs , usually accompanied by lower limb paresthesias . These symptoms worsen at rest , are relieved by activity , and are worse at night . Previous studies have suggested that dopaminergic drugs such as L-dopa and dopamine agonists , as well as benzodiazepines and opioids , can treat RLS successfully . The purpose of this study was to test the clinical efficacy of ropinirole , a D2/D3 agonist , in the treatment of RLS in a double-blind , short-term , placebo-controlled clinical trial . PATIENTS AND METHODS After undergoing successful open-label titration and dose adjustments with ropinirole for RLS symptoms over a period of 4 weeks , 22 RLS patients ( mean age=50.8 ; mean duration of symptoms=26.1 years ) were r and omized to receive either placebo ( n=13 ) or ropinirole ( n=9 ) for 2 additional weeks . Outcome measures included assessment of periodic leg movements in sleep ( PLMS ) recorded with nocturnal polysomnography and RLS symptoms as assessed with the International Restless Legs Syndrome Study Group ( IRLSSG ) Rating Scale . Secondary outcomes included sleep macroarchitecture . RESULTS Results indicated that relative to placebo , ropinirole , at a mean dose of 1.4 mg HS significantly decreased PLMS and RLS symptoms . Sleep macroarchitecture did not change . Side effects were typical of all dopamine agonists and were dose related . The majority of patients elected to continue treatment with ropinirole upon study completion . CONCLUSIONS Ropinirole successfully treated long-st and ing RLS and can be considered a viable short-term treatment for this condition Summary A double-blind r and omized crossover study of 0.125 mg Pergolide ( Lilly ® ) at bedtime versus 250 mg L-Dopa + Carbidopa ( Roche ® ) was conducted in 16-day phases in 11 patients with idiopathic restless legs syndrome . Two patients reported a partial and 9 patients a complete relieve of motor restlessness while receiving Pergolide . Only 1 patient experienced an improvement of restlessness after L-Dopa . The patients showed polysomnographically a mean decrease in NMS cluster disturbed time by 45 % from control on L-Dopa ( p < 0.025 ) and by 79 % from control on Pergolide ( p < 0.001 ) . In addition , Pergolide increased the total sleep time compared to L-Dopa ( p < 0.05 ) . In conclusion , the dopamine agonist Pergolide is superior to L-Dopa in the treatment of RLS and NMS Abstract .We aim ed to compare the efficacy of valproic acid ( VPA ) on paresthesias and sleep in RLS  to that of levodopa ( LD ) . Twenty patients with idiopathic restless legs syndrome ( RLS ) were treated with 600 mg slow-release VPA and 200 mg slow-release LD+50 mg benserazid in a r and omized , placebo-controlled , cross-over , double-blind setting with polysomography ( PSG ) at the end of each 3-week treatment periods . There was no major difference between the efficacy of valproic acid or LD . Periodic leg movements in sleep ( PLMS ) and PLM arousal index ( PLMAI ) significantly decreased with LD ( p ≤ 0.005 ) . However , LD , but not VPA , significantly increased arousals not associated with PLMS ( p = 0.002 ) . Decrease of intensity and duration of RLS symptoms were more pronounced with VPA ( p ≤ 0.022 ) than with LD ( NS ) . We conclude that slow-release VPA provides a treatment alternative for RLS Restless legs syndrome ( RLS ) is a neurological condition with significant impact on sleep and quality of life ( QoL ) . This double-blind , r and omized , 12-week , multinational study compared the efficacy and safety of ropinirole and placebo in RLS . In total , 267 out patients with moderate-to-severe RLS were r and omly 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 question naire . 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 Objectives ‐ Nocturnal disabilities leading to fragmented sleep arising from parkinsonian off period related complications are common , under‐reported and are difficult to treat . In this study , we evaluate the use of nocturnal continuous subcutaneous overnight apomorphine infusion in Parkinson 's disease and restless legs syndrome . Methods ‐ Six parkinsonian patients and 2 patients with restless legs syndrome with nocturnal disabilities refractory to conventional oral therapy were assessed using a sleep diary while on st and ard treatment and during nocturnal apomorphine infusion . Three patients agreed to assessment s during placebo infusion with normal saline . Results ‐ Apomorphine led to a dramatic reduction of nocturnal awakenings , nocturnal off periods , pain , dystonia and nocturia in parkinsonian patients . In patients with restless legs syndrome  , apomorphine reduced nocturnal discomfort , reduced leg movements and improved pain and spasm scores significantly . Placebo infusion reproduced pain , nocturnal spasms and sleep disruption . Conclusion ‐ This study suggests that overnight apomorphine infusion may be effective in overcoming refractory nocturnal disabilities in selected patients with Parkinson 's disease and restless legs syndrome 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 r and omized 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 0.50 mg 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 Restless legs syndrome ( RLS ) and periodic limb movements in sleep ( PLMS ) are disorders that are common and disturbing to uremic patients . The treatment of these is problematic . Eight patients on chronic hemodialysis and continuous peritoneal dialysis completed a double-blind placebo-controlled crossover study using incremental doses of pergolide up to 0.25 mg at bedtime for treatment of RLS and sleep disruption . Five patients ( 62.5 % ) noted subjective improvement in restless legs symptoms and sleep quality . Objective results were improved only slightly by treatment . The percentage of the first hour in bed during which leg movements occurred decreased from 20.5 + /- 6.0 to 11.5 + /- 3.3 , p < 0.05 . However , findings during sleep were less positive . The following measures were not significant between placebo and treatment : leg movements per hour of sleep [ 53.7 + /- 22.3 vs 35.8 + /- 11.8 ( p = 0.2 ) ] ; and percentage of sleep time spent with leg movements [ 5.5 % + /- 3.2 vs 4.4 % + /- 1.4 ( p = 0.37 ) ] . Patients continued to have very disrupted sleep , and we could not document an objective improvement in sleep architecture . 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 objective ly decreased leg movements during the first hour in bed , objective ly sleep continued to be disrupted . In this small patient group , the response to pergolide was not uniform , and further investigation is required to test effectiveness at higher doses Objectives : 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 . Methods : In this multicenter , double-blind , r and omized , 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 ≥ 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 . Results : 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 ≤ 0.05 for days 2 - 7 LOCF ) and at week 12 LOCF ( P < 0.001 ) . Conclusions : Ropinirole is associated with consistent early and sustained improvements in the symptoms of RLS , as rated by patients and physicians We report the first large-scale double-blind , r and omly assigned study to compare two active dopaminergic therapies for Restless Legs Syndrome ( RLS ) , the dopamine agonist cabergoline ( CAB ) and levodopa/benserazide ( levodopa ) .  Patients with idiopathic RLS were treated with fixed daily doses of 2 or 3 mg CAB or 200 or 300 mg levodopa for 30 weeks . Efficacy was assessed by changes in the IRLS ( International RLS Severity Scale ) and by time to discontinuation of treatment due to loss of efficacy or augmentation .  361 of 418 screened patients ( age 58 + /- 12 years , 71 % females ) were r and omly assigned and treated ( CAB : n = 178 ; levodopa : n = 183 ) in 51 centers of four European countries . Baseline IRLS total score was 25.7 + /- 6.8 . The baseline-adjusted mean change from baseline to week 6 in IRLS sum score was d = -16.1 in the CAB group and d = -9.5 in the levodopa group ( d = -6.6 , P < 0.0001 ) . More patients in the levodopa group ( 24.0 % ) than in the CAB group ( 11.9 % , P = 0.0029 , log-rank test ) discontinued because of loss of efficacy ( 14.2 % vs. 7.9 % , P = 0.0290 ) or augmentation ( 9.8 % vs. 4.0 % , P = 0.0412 ) . Adverse events ( AEs ) occurred in 83.1 % of the CAB group and in 77.6 % of the levodopa group . In both groups , most frequent AEs were gastrointestinal symptoms ( CAB : 55.6 % , levodopa : 30.6 % , P < 0.0001 ) . This first large-scale active controlled study in RLS showed superior efficacy of cabergoline versus levodopa after a 30-week long-term therapy . Tolerability was found more favorable with levodopa than with cabergoline Background : Restless legs syndrome ( RLS ) is characterized by leg paresthesia associated with an irresistible urge to move . Currently used dopaminergic agents , such as levodopa , pergolide , and bromocriptine , offer incomplete control of sensory and motor symptoms and induce severe side effects . Objective : To assess the safety and efficacy of pramipexole , a full D3-receptor agonist , in the treatment of RLS . Methods : Ten RLS patients were studied before and after two 1-month treatments ( placebo and pramipexole ) administered in a double-blind crossover fashion . The severity of sensory and motor manifestations was assessed by 1 week of home question naires and 2 consecutive nights of sleep laboratory recordings . The indexes of periodic leg movement during sleep ( PLMS ) and during wakefulness ( PLMW ) were used as primary outcome variables . Results : Pramipexole dramatically reduced the PLMS index to normal values ( Wilcoxon , p = 0.005 ) . The PLMW index was also significantly reduced ( Wilcoxon , p = 0.007 ) . Pramipexole also alleviated leg discomfort at bedtime and during the night as measured by the home question naires . Conclusions : Pramipexole is the most potent therapeutic agent ever tested for RLS . Measures of both sensory and motor functions returned to normal values after treatment . Moreover , these results further support the hypothesis that D3 receptors play a major role in the physiopathology of this condition OBJECTIVE 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 , r and omized , placebo-controlled , multicenter study ( NCT00275236 ) . METHODS Sixty-seven ( 46 rotigotine , 21 placebo ) subjects applied rotigotine ( maximum 3mg/24h ) or placebo patches once-daily during a 4-week maintenance period ; efficacy evaluations used polysomnographic measures and clinician/patient ratings . RESULTS Mean PLM index ( PLMI ; PLM/h time in bed ) decreased more with rotigotine ( 50.9/h to 8.1/h ) than with placebo ( 37.4/h to 27.1/h ; adjusted treatment ratio 4.25 ( 95 % CI [ 2.48,7.28 ] , p<0.0001 ) . PLM during sleep with arousal index ( PLMSAI ; 8.57/h to 2.47/h under rotigotine , 6.5/h to 4.95/h under placebo ; adjusted treatment difference : -3.12 ( 95 % CI [ -5.36 , -0.88 ] , p=0.0072 ) also improved more under rotigotine . At end of maintenance , 39 % of rotigotine subjects had PLMI levels < 5/h and 26 % showed no RLS symptoms ( IRLS=0 ) , whereas no placebo subject met these criteria . Common drug-related adverse events for rotigotine and placebo included nausea ( 21.7%/4.8 % ) , headache ( 17.4%/14.3 % ) , application site reactions ( 17.4%/4.8 % ) , and somnolence ( 10.9%/9.5 % ) ; most were mild to moderate in intensity . CONCLUSIONS Rotigotine transdermal patch was efficacious and well tolerated in the short-term treatment of RLS motor symptoms and associated sleep disturbances Objective : To evaluate the short- and long-term safety and efficacy of pergolide therapy for restless legs syndrome ( RLS ) in a double-blind , placebo-controlled , r and omized trial ( Pergolide European Australian RLS [ PEARLS ] study ) . Methods : We r and omized 100 patients with idiopathic RLS were r and omized to pergolide , 0.25 to 0.75 mg , in the evening or placebo for 6 weeks ( phase 1 ) ; thereafter , patients with response on the Patient Global Impression ( PGI ) scale continued on double-blind pergolide or placebo , and nonresponders received open-label pergolide up to 1.5 mg/d for 12 months of treatment ( phase 2 ) . Sleep efficiency ( SE ) and periodic limb movements during sleep ( PLMS ) arousal index were monitored by central ly evaluated polysomnography ( PSG ) . The severity of RLS was assessed using the vali date d International RLS Scale ( IRLS ) . Results : In phase 1 ( change from baseline to week 6 ) , pergolide  reduced PLMS arousal index vs placebo ( mean ± SD , −12.6 ± 10.0 vs −3.6 ± 15.9 ; p = 0.004 ) , and SE did not improve ( mean ± SD , + 11.3 ± 11.9 % vs + 6.1 ± 18.6 % ; p = 0.196 ) . Pergolide  improved RLS severity score ( −12.2 ± 9.9 vs −1.8 ± 7.5 placebo ; p < 0.001 ) and was associated with a higher PGI response ( 68.1 % vs 15.1 % ; p < 0.001 ) and improvements in periodic limb movements ( PLM ) index , PGI improvement scale , Clinical Global Impression improvement , and IRLS ( all p < 0.001 ) , patient-reported SE ( p = 0.019 ) , and quality of sleep ( p < 0.001 ) . After 12 months ( phase 2 ) , double-blind pergolide maintained improvements in PLMS arousal index and PLM index . Placebo patients switched to open-label pergolide in phase 2 exhibited marked improvements in these measures that were maintained at 12 months . Pooled results from the blinded and open-label pergolide groups demonstrated improvements at 12 months in the PLMS arousal index ( p = 0.028 ) and PLM index ( p < 0.0001 ) compared with placebo . Nausea and headache were more frequent with pergolide than with placebo treatment . Conclusions : Pergolide substantially improves periodic limb movement measures and subjective sleep disturbance associated with restless legs syndrome . Low-dose pergolide was well tolerated and maintained its efficacy in the long term Efficacy and safety of the dopamine agonist rotigotine ( RTG ) was investigated in patients with moderate to severe idiopathic restless legs syndrome ( RLS ) , including daytime symptoms . Three fixed doses of rotigotine ( 1.125 mg , 2.25 mg , and 4.5 mg ) and placebo were applied by patches ( size , 2.5 cm2 per 1.125 mg ) in a double-blind , r and omized , parallel-group , multicenter , 1-week , proof-of-principle trial . The primary efficacy measure was the total score on the International Restless Legs Syndrome Scale ( IRLS ) . Additionally , the RLS-6 scale , the Clinical Global Impressions ( CGI ) , and a sleep diary were used . Of 68 enrolled patients , 63 ( mean age , 58+/- ; 9 years ; 64 % women ) were r and omly assigned . RLS severity improved related to dose by 10.5 ( 1.125 mg RTG/die ; P = 0.41 ) , 12.3 ( 2.25 mg RTG/die ; P = 0.18 ) , and 15.7 points ( 4.5 mg RTG/die ; P < 0.01 ) on the IRLS compared to placebo ( 8 points ) . According to the RLS-6 scales , daytime symptoms significantly improved with all rotigotine doses . The CGI items supported the favorable efficacy of the 4.5-mg dose . Skin tolerability of the patches and systemic side effects were similar between rotigotine and placebo . This pilot study suggests that continuous delivery of rotigotine by means of a patch may provide an effective and well-tolerated treatment of RLS symptoms both during night and day Objective : To assess the efficacy of pergolide in the treatment of restless legs syndrome ( RLS ) . Methods : A r and omized , double-blind , parallel-treatment evaluation of pergolide versus placebo in patients with RLS was performed . Sixteen patients seen in the Sleep Disorders Center who met the clinical criteria for RLS were enrolled in the study . Treatment was either placebo ( n = 8) or pergolide ( n = 8) , which was on a self-adjusted schedule that ranged from 0.05 to 0.65 mg/day . Outcome variables included the patient 's rating of symptom improvement , duration of RLS symptoms throughout the day , and objective sleep assessment s from an all-night polysomnogram ( percent sleep efficiency and periodic leg movements ) . Baseline was assessed for 2 days before starting treatment . Dose adjustments were made over the first 14 days and were then held constant for 5 days , with repeat assessment for treatment effects on the last 2 days of treatment ( days 17 and 18 ) . Results : As a group , pergolide recipients showed significant improvement clinical ly and statistically in all outcome measures when compared with baseline or with placebo treatment . On the other h and , placebo treatment led to no significant improvements in any outcome measures . Conclusions : Pergolide treatment significantly improved clinical symptoms and sleep efficiency , and reduced periodic limb movements of sleep in patients with RLS We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome ( RLS ) for 6 weeks . Overall , 345 patients were r and omly 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 assessment s : 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 ) assessment s 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 OBJECTIVE To compare the efficacy , safety and tolerability of sumanirole with placebo in patients with idiopathic restless legs syndrome ( RLS ) . METHODS In this double-blind , placebo-controlled , r and omized , parallel-group , dose-response study , 270 patients with idiopathic RLS were enrolled and r and omized to receive sumanirole 0.5 , 1.0 , 2.0 , or 4.0 mg , or placebo . The primary efficacy endpoint was mean change of the total score of the International Restless Legs Scale ( IRLS-10 ) , a 10-item scale , from baseline to end of maintenance . Secondary assessment s included polysomnography ( PSG ) variables . RESULTS Treatment with sumanirole was well tolerated . Mean change in IRLS-10 showed no statistically significant change compared with placebo at any dose , although the mean change with the 4.0-mg dose was numerically greater than the other doses and placebo . PSG variables , specifically the periodic leg movements during sleep , showed statistically significant dose-related improvement in favor of sumanirole . Consistent with earlier multinational , multicenter studies in RLS , high placebo response rates were seen with IRLS-10 but not with PSG variables . CONCLUSIONS Given data published in Parkinson 's disease , the dose range of sumanirole selected here may have been too low . Alternatively , dopamine D(2 ) selective agents could be intrinsically less effective than agonists with combined D(2)/D(3 ) activity . Sumanirole demonstrated an excellent safety profile Periodic limb movements ( PLM ) cause sleep disorders and daytime symptoms and are frequently associated with restless legs syndrome ( RLS ) . Treatment of RLS with increased PLM during sleep ( PLMS ) has been evaluated in studies limited in size , methodology and study length . This long-term , placebo-controlled , multi-center , study with polysomnography ( PSG ) recordings has been design ed in order to assess efficacy and safety parameters of pergolide treatment in RLS . This novel approach for a study was created to assure consistently high quality of sleep recording and analysis . Using defined criteria , 21 sleep centers were approved for the study after a pilot phase . Seventeen centers with 16 different PSG systems r and omized 100 patients .  Digital sleep recordings from 4 visits ( baseline , 6 weeks , 6 months , 1 year ) were su bmi tted to one central evaluation center following previously defined st and ardized operating procedures . Visual scoring of all recordings was performed by one independent scorer . Reliability of scoring was evaluated for 20 r and omly selected baseline recordings . The mean epoch by epoch agreement for sleep stages was 88 % ( range 81 - 96 % ) , mean arousal re-scoring differed by 0.5 ( range : -16 to 20 ) , and mean PLM index re-scoring differed by 0.1 ( range : -1.5 to 2.1 ) . Using one scorer with a demonstrated high reliability in PSG scoring for all sleep recordings was very effective in terms of study cost , study duration , and data quality BACKGROUND In a pilot placebo-controlled study , low dosages of 0.5 - 2mg/24h rotigotine showed a dose-dependent beneficial effect in restless legs syndrome ( RLS ) patients . METHODS Efficacy and safety of the dopamine agonist rotigotine , formulated as a once-daily transdermal system ( patch ) , was investigated for five fixed dosages and compared to placebo in patients with idiopathic RLS in a double-blind , r and omized , parallel-group , multicenter , six-week dose-finding trial . Primary efficacy measure was the total score of the International RLS Severity Scale ( IRLS ) ; in addition , the RLS-6 scales and the Clinical Global Impressions ( CGI ) were administered . RESULTS Of 371 enrolled patients , 341 patients ( mean age 58+/-10years , 67 % females ) were r and omized . The IRLS total score improved between baseline and end of the six-week treatment period by -10.6 ( 0.5mg/24h rotigotine ; patch area 2.5cm2 ) , -15.1 ( 1mg/24h ; 5cm2 ) , -15.7 ( 2mg/24h ; 10cm2 ) , -17.5 ( 3mg/24h ; 15cm2 ) , and -14.8 ( 4mg/24h , 20cm2 ) as compared to placebo ( -9.2 ) . The hierarchical statistical test procedure demonstrated superiority of rotigotine over placebo for 4mg/24h , 3mg/24h , 2mg/24h , and 1mg/24h , with p-values of 0.0013 , < 0.0001 , 0.0003 , and 0.0004 , respectively . Only the 0.5mg/24h dose was not different compared to placebo ( p=0.2338 ) . The CGI and the RLS-6 severity items supported the efficacy of the rotigotine doses beyond 0.5mg/24h . The most frequent side effects were application site reactions and nausea and tended to be more frequent with higher doses . CONCLUSIONS This dose-finding trial identified the range for a maintenance dose of rotigotine from 1mg/24h to 3mg/24h . The lowest dose was ineffective and , with the highest dose , no additional benefit was observed BACKGROUND Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome . Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome . METHODS In this r and omised , double-blind , placebo-controlled trial , 458 patients with moderate-to-severe idiopathic restless legs syndrome ( average baseline International Restless Legs Syndrome Study Group severity rating scale [ IRLS ] sum score of 28.1 ) were r and omly assigned to receive transdermal rotigotine 1 mg over 24 h ( n=115 ) , 2 mg over 24 h ( n=112 ) , or 3 mg over 24 h ( n=114 ) , or to receive placebo ( n=117 ) . Study medication was delivered via patches , applied once a day for 6 months . R and omisation was done with a computer-generated r and omisation list , stratified by centre . Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions ( CGI ) item 1 score , assessed by analysis of covariance in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00136045 . FINDINGS Efficacy analyses were done on 112 patients in the 1 mg group , 109 in the 2 mg group , 112 in the 3 mg group , and 114 in the placebo group . Mean change in IRLS sum score from baseline at the end of the maintenance phase was -13.7 ( SE 0.9 ) in the 1 mg group , -16.2 ( 0.9 ) in the 2 mg group , -16.8 ( 0.9 ) in the 3 mg group , and -8.6 ( 0.9 ) in the placebo group ( p<0.0001 for treatment difference vs placebo with each dose ) . Mean change in CGI item 1 score from baseline at the end of the maintenance phase was -2.09 ( 0.14 ) in the 1 mg group , -2.41 ( 0.14 ) in the 2 mg group , -2.55 ( 0.14 ) in the 3 mg group , and -1.34 ( 0.14 ) in the placebo group ( p<0.0001 for treatment difference vs placebo with each dose ) . Skin reactions , mostly mild or moderate , were seen in 145 ( 43 % ) of 341 patients who received rotigotine and in two ( 2 % ) of 117 who received placebo .  Ten patients had serious adverse event that were deemed to be related to rotigotine :  elevation of liver enzymes ( one patient ) , worsening of tinnitus ( one patient ) , non-response to anticoagulation ( one patient ) , electrocardiogram changes ( one patient ) , and application-site reactions ( six patients ) . No admissions to hospital were needed for the application-site reactions , and they all resolved within a short time of patch removal without any other therapeutic intervention . The rate of typical dopaminergic side-effects in patients who received rotigotine was low ; no signs of augmentation were noted . INTERPRETATION 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome . FUNDING Schwarz Biosciences OBJECTIVE To evaluate the efficacy of pramipexole on polysomnographic measures , patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome ( RLS ) . METHODS Patients with moderate to severe RLS having periodic limb movements in bed index (PLMI)>or=5 were r and omly assigned to receive pramipexole or placebo in a 6-week , double-blind , placebo-controlled study with forced titration from 0.125 to 0.75mg/day . Both  polysomnography ( PSG ) and the  suggested immobilization test ( SIT )  were performed at baseline and 6weeks after starting treatment . RESULTS The analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group ( p=0.0019 ) . In all patients , variables on SIT did not show any differences between the two groups , whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline > or=15 . 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 . CONCLUSIONS 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 Objective : To evaluate the prevalence , characteristics , and treatment of  restless legs syndrome ( RLS ) in France . Methods : In this population -based survey , face-to-face home interviews were conducted among a r and om sample of 10,263 French adults . A French translation of the four features defined by the International RLS Study Group in 1995 was used to assess the prevalence of symptoms consistent with a diagnosis of RLS . Data on severity of symptoms and their management were also collected . Results : The 12-month prevalence of RLS symptoms in the French adult population was estimated to be 8.5 % ( 95 % CI 8.0 % , 9.0 % ) , with a higher prevalence ( p < 0.001 ) observed in women ( 10.8 % ) than in men ( 5.8 % ) . Prevalence increases with age until 64 years and decreases thereafter in both sexes . Half of the identified subjects reported symptoms once a week at least . Symptoms were more severe in subjects reporting symptoms once a week at least compared to subjects with less frequent symptoms . In this group , half of the subjects reported a family history , the age at onset was earlier , and severity of symptoms higher . RLS had been previously diagnosed in only 5.3 % of the subjects who reported previous medical diagnosis , and recommended RLS drug  treatment was received by 3.4 % of the 28.7 % currently treated subjects . Conclusions : Restless legs syndrome ( RLS ) occurred in 10 % of women and 5 % of men . RLS prevalence decreases after the age of 64 . RLS is often underdiagnosed and few subjects receive recommended RLS drug treatment The European Restless Legs Syndrome ( RLS ) Study Group ( EURLSSG ) is an association of European RLS experts who are actively involved in RLS research . A major aim of the Study Group is the development and continuous improvement of st and ards for diagnosis and treatment of RLS . Several members developed study design s and evaluation methods in investigator-initiated trials early in the 1990s , and all members have since contributed to many pivotal and nonpivotal drug trials for the treatment of RLS . The recommendations on clinical investigations of pharmacological treatment of RLS patients summarize the group 's expertise and knowledge acquired through clinical trials . The recommendations primarily address how to plan and conduct confirmatory , r and omized clinical studies in patients with idiopathic RLS . Advice is presented for the diagnosis of RLS and clinical and polysomnographic inclusion and exclusion criteria . Primary and secondary endpoints for an evaluation of efficacy are based on a critical description of vali date d methods for both short- and long-term trials , also in special population s ( children , pregnant women , elderly patients ) . The recommendations include the assessment of augmentation . Finally , general issues including the evaluation of safety and tolerability , as well as specific neurological and cardiovascular risks and sleep attacks/daytime somnolence , are discussed . The aim of these recommendations is to support research groups or pharmaceutical companies in the design of optimized study protocol Comorbid depressive symptoms in restless legs syndrome ( RLS ) remain a treatment challenge , as some antidepressants aggravate RLS symptoms . Preliminary data in depressive patients suggest antidepressant properties of ropinirole . The present study investigates the effects of ropinirole immediate release ( IR ) on depressive symptoms and RLS severity . A multicenter , placebo-controlled , double-blind r and omized ( 3:1 ) study was performed including patients with moderate to severe idiopathic RLS and at least mild depressive symptoms .  Ropinirole IR ( in flexible doses up to 4 mg/day ) or placebo was given for 12 weeks including an uptitration phase of 7 weeks . Visits were scheduled at screening , baseline , and weeks 1 , 4 , and 12 with additional telephone contacts for dosing decisions . The modified intent to treat population comprised 231 patients ( 171 ropinirole , 60 placebo ) .  The MADRS ( Montgomery – Asberg Depression Rating Scale ) scores decreased from baseline to week 12 from 18.8 to 8.7 in the ropinirole group and from 18.4 to 12.1 in the placebo group ( primary endpoint , adjusted mean treatment difference −3.6 ( 95 % CI : −5.6 to −1.6 , significance in favor of ropinirole : P < 0.001 ) . The superiority of ropinirole compared to placebo was confirmed by the Hamilton Scale for Depression and Beck Depression Inventory-II scores . RLS severity scores ( IRLS ) decreased by 14.7 ( ropinirole ) and by 9.9 ( placebo , P < 0.001 ) points . Three out of four subdomains of the Medical Outcomes Study Sleep Scale improved significantly . The findings indicate that mild to moderate depressive symptoms should not be treated before sufficient therapy for RLS . Antidepressant medication can be necessary if depression symptoms still persist even if RLS symptoms are ameliorated BACKGROUND The treatment with the long-acting dopamine D1/D2 receptor agonist pergolide has been proven as very effective in lowering the frequency of periodic leg movements ( PLM ) in patients with restless legs syndrome ( RLS ) . To further investigate the influence of this potent dopaminergic drug on the microstructure of rapid eye movement ( REM ) and non-REM sleep EEG we established a quantitative analysis of the EEG data . METHODS The study group consisted of 15 patients with primary RLS ( mean age 57.1+/-10.1 years ) who were a subgroup of patients within a double-blind r and omized crossover treatment study with pergolide versus placebo .  The polysomnographic recordings were analyzed visually and su bmi tted to a quantitative EEG analysis ( fast Fourier transformation ) . RESULTS The pergolide treatment induced a significant reduction of the spectral power in the delta range ( 0.78 - 3.9 Hz ; P<0.05 ; t-test ) during SWS , as well as a significant reduction of PLMs . In addition , we observed a decrease in the sigma EEG activity ( 12.1 - 14.8 Hz ; P<0.03 ) during non-REM sleep and stage 2 sleep . The visual sleep scoring revealed a significant increase in stage 2 sleep ( P<0.005 ) , whereas wakefulness was markedly diminished ( P<0.001 ) . The REM sleep parameters including the EEG power spectrum remained unchanged . CONCLUSIONS The treatment with pergolide markedly improved the sleep quality  in RLS patients but did not restore SWS including the spectral power in the lower frequencies . Our results suggest that the dopamine agonist pergolide interferes with the subcortical mechanisms regulating the process of EEG synchronization during non-REM sleep Summary . Pergolide has proven significantly superior to L-dopa plus peripheral decarboxylase inhibitor in short-term therapy of RLS/NMS . We now first present long-term follow-up sleep data showing its lastingly good effects after averagely 517 treatment days Objective : To assess the efficacy and safety of the dopamine agonist cabergoline in the treatment of patients with idiopathic restless legs syndrome ( CATOR study ) . Methods : Patients with moderate to severe restless legs syndrome ( RLS ) were r and omly assigned to cabergoline ( single evening dose : 2 mg ) or placebo and treated for 5 weeks in a double-blind , multicenter polysomnography ( PSG ) trial . The primary efficacy measures were the periodic leg movements during sleep arousal index ( PLMS-AI ) and sleep efficiency . These and further PSG variables were monitored by central ly evaluated PSG . Severity of RLS was assessed using the International RLS Study Group Severity Scale ( IRLS ) , the RLS-6 scales , the Sleep Question naire Form A ( SF-A ; quality of sleep ) , and the Quality of Life for RLS question naire . Results : Forty-three patients were treated and 40 patients were evaluated with PSG ( age 56 ± 10 years , 73 % women ) . Cabergoline was superior to placebo in terms of the PLMS-AI ( −17.7 ± 16.4 vs −4.5 ± 20.0 placebo ; p = 0.0024 ) , sleep efficiency ( + 6.2 ± 13.9 % vs + 3.3 ± 11.7 % ; p = 0.0443 ) , PLMS index ( p = 0.0014 ) , PLM index ( p = 0.0012 ) , and total sleep time ( p = 0.0443 ) . Improvements in IRLS total score ( −23.7 ± 11.2 vs −7.9 ± 11.0 placebo ; p = 0.0002 ) , RLS-6 severity scales during the night ( p = 0.0010 ) and during the day ( p = 0.0018 ) , Clinical Global Impressions severity item ( p = 0.0003 ) , sleep quality ( p = 0.0180 ) , SF-A sleep quality ( p = 0.0371 ) , and QoL-RLS ( p = 0.0247 ) were larger in patients treated with cabergoline compared with the placebo group . Adverse events were only mild and well-known side effects of dopamine agonists . Conclusion : Single-evening cabergoline is an efficacious and well-tolerated short-term therapy for sensorimotor symptoms of restless legs syndrome and associated sleep disturbances 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 r and omized 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 Objective : To assess the efficacy and tolerability of the nondopaminergic agent XP13512/GSK1838262 in adults with moderate to severe primary restless legs syndrome ( RLS ) . Methods : Patient Improvements in Vital Outcomes following Treatment in Restless Legs Syndrome I was a 12-week , multicenter , r and omized , double-blind , placebo-controlled trial of XP13512 1,200 mg or placebo taken once daily at 5:00 pm with food . Co primary endpoints were mean change from baseline International Restless Legs Scale ( IRLS ) total score and proportion of investigator-rated responders ( very much improved or much improved on the Clinical Global Impression – Improvement scale ) at week 12 ( last observation carried forward ) . Tolerability was assessed using adverse events , vital signs , and clinical laboratory parameters . Results : A total of 222 patients were r and omized ( XP13512 = 114 , placebo = 108 ) and 192 patients ( XP13512 = 100 , placebo = 92 ) completed the study . At week 12 , the mean change from baseline IRLS total score was greater with XP13512 ( −13.2 ) compared with placebo ( −8.8 ) . Analysis of covariance , adjusted for baseline score and pooled site , demonstrated a mean treatment difference of −4.0 ( 95 % confidence interval [ CI ] , −6.2 to −1.9 ; p = 0.0003 ) . More patients treated with XP13512 ( 76.1 % ) were responders compared with placebo ( 38.9 % ; adjusted OR 5.1 ; 95 % CI , 2.8 to 9.2 ; p < 0.0001 ) . Significant treatment effects for both co primary measures were identified at week 1 , the earliest time point measured . The most commonly reported adverse events were somnolence  ( XP13512 27 % , placebo 7 % ) and dizziness  ( XP13512 20 % , placebo 5 % ) , which were mild to moderate in intensity and generally remitted . Conclusions : 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 Objective : To assess the efficacy and safety of the dopamine agonist cabergoline ( CAB ) in patients with restless legs syndrome ( RLS ) . Methods : Patients with moderate to severe RLS were r and omized into four groups receiving placebo , 0.5 mg , 1 mg , or 2 mg CAB once daily in a double-blind , placebo-controlled , multicenter dose-finding trial followed by an open long-term extension trial of 47 weeks . Efficacy was assessed with the RLS-6 scales and International RLS Study Group severity scale ( IRLS ) . Results : A total of 85 patients ( age 56 ± 10 years , 71 % females ) were treated . Severity of RLS-6 scale symptoms during the night ( the primary endpoint ) was markedly improved by all CAB doses compared to placebo ( placebo : −1.4 ± 3.1 , 0.5 mg CAB : −4.2 ± 3.0 [ p = 0.0082 ] , 1.0 mg CAB : −4.0 ± 2.9 [ p = 0.0040 ] , 2.0 mg CAB : −4.8 ± 3.7 [ p = 0.0026 ] ) . Similar results were found for the RLS severity at bedtime and during the day , IRLS , and satisfaction with sleep . A stable , clinical ly relevant improvement was achieved in all efficacy measures ( severity during the night : change between last assessment and baseline : −5.6 ± 2.5 , rate of remission : 71.2 % ) throughout 1 year with a mean CAB dose of 2.2 mg per day . During long-term treatment , 6 of 66 treated patients were affected ( n = 2 ) or possibly affected ( n = 4 ) by mild augmentation . Under CAB therapy up to 1 year , 11 of 85 patients discontinued treatment due to a drug-related adverse event . Conclusions : Cabergoline is an efficacious and well-tolerated option for the treatment of restless legs symptoms during the night and the day Although dopamine agonists are becoming first-line therapy for restless legs syndrome ( RLS ) , few reports describe treatment periods exceeding 12 weeks . Here , 150 RLS patients who had responded to pramipexole during a 6-month run-in period ( mean dose , 0.50 mg ) were r and omly assigned to receive placebo or continue receiving pramipexole at an individually optimized dose of 0.125 to 0.75 mg/day for a further 3 months . Patients switched to placebo reached the primary endpoint ( a predefined worsening on both the Clinical Global Impressions-Global Improvement scale and the International RLS Study Group Rating Scale ) significantly more often than patients who continued to receive pramipexole ( 85.5 % vs. 20.5 % ; P < 0.0001 ) . They also reached the primary endpoint faster , in 5 versus 42 days to a Kaplan-Meier survival estimate of 0.85 and 7 versus > 84 days to an estimate of 0.5 . Over the total 9 months , clinician and patient ratings of symptoms , sleep , and quality of life identified no decline in pramipexole 's benefit or tolerability . The great majority of adverse events ( AEs ) were mild or moderate , and of expected types . Augmentation was considered an AE , but in this population of responders it did not occur Background : Open clinical trials indicate that low doses of pergolide , a long-acting D1 and D2 dopamine agonist , lead to a reduction in the symptoms of restless legs syndrome ( RLS ) with subjective improvement in sleep quality . Objective : To assess the therapeutic efficacy of pergolide in improving sleep and subjective measures of well-being in patients with idiopathic RLS using polysomnography and clinical ratings . Methods : In a r and omized , double-blind , placebo-controlled crossover design we enrolled 30 patients with idiopathic RLS according to the criteria of the International RLS Study Group . All patients were free of psychoactive drugs for at least 2 weeks before the study . Patients were monitored using polysomnography , clinical ratings , and sleep diaries at baseline and at the end of a 4-week pergolide or placebo treatment period . The initial dosage of 0.05 mg pergolide was increased to the best subjective improvement paralleled by 20 mg domperidone tid . Results : At a mean dosage of 0.51 mg pergolide as a single daily dose 2 hours before bedtime , there were fewer periodic leg movements per hour of time in bed ( 5.7 versus 54.9 , p < 0.0001 ) , and total sleep time was significantly longer ( 373 versus 261 minutes , p < 0.0001 ) . Ratings of subjective sleep quality , quality of life , and severity of RLS were improved significantly without relevant adverse events . Conclusion : Pergolide given as a single low-to-medium bedtime dose in combination with domperidone provides a well-tolerated and effective treatment of sensorimotor symptoms and sleep disturbances in patients with primary RLS Objective To assess the effects of gabapentin on sensory and motor symptoms in patients with restless legs syndrome ( RLS ) . Methods Patients with RLS ( 22 idiopathic , 2 secondary to iron deficiency ) were r and omized and treated for 6 weeks with either gabapentin or placebo . After a 1-week washout they crossed over to the alternative treatment for 6 weeks . Patients were rated at baseline and at scheduled intervals by the RLS Rating Scale , Clinical Global Impression , pain analogue scale , and Pittsburgh Sleep Quality Index . At the end of each treatment period , all-night polysomnography  was performed . Results Compared to placebo , gabapentin was associated with reduced symptoms on all rating scales . In addition , sleep studies showed a significantly reduced periodic leg movements during sleep ( PLMS ) index and improved sleep architecture ( increased total sleep time , sleep efficiency , and slow wave sleep , and decreased stage 1 sleep ) . Patients whose symptoms included  pain  benefited most from gabapentin . The mean effective dosage at the end of the 6-week treatment period was 1,855 mg , although therapeutic effects were already observed at the end of week 4 ( 1,391 mg ) . Conclusions Gabapentin improves sensory and motor symptoms in RLS and also improves sleep architecture and PLMS The authors performed a double-blind , placebo-controlled , crossover study of ropinirole ( 0.5 to 6.0 mg/day ) for restless legs syndrome ( RLS ) . The RLS Rating Scale score improved ( p < 0.001 ) from a mean ( SD ) of 25 ( 7 ) during placebo treatment to 13 ( 12 ) during ropinirole treatment . Eight of the 22 patients had complete resolution of symptoms on ropinirole . Adverse events included nausea and dizziness . Ropinirole was effective and well tolerated for treating the symptoms of RLS
BACKGROUND According to clinical guidelines , dopamine agonists are the first-line treatment of restless legs syndrome ( RLS ) .
OBJECTIVES To evaluate efficacy and safety of dopamine agonists for RLS .