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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2015  |  Volume : 26  |  Issue : 2  |  Page : 271-278
Gabapentin versus levodopa-c for the treatment of restless legs syndrome in hemodialysis patients: A randomized clinical trial


1 Department of Neurology; Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Department of Neurology, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 Department of Nephrology, Kermanshah University of Medical Sciences, Kermanshah, Iran
4 Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

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Date of Web Publication3-Mar-2015
 

   Abstract 

To compare the efficacy of gabapentin and levodopa-c (Levodopa/Carbidopa) in reducing restless leg syndrome (RLS) symptoms and sleep problems in hemodialysis patients with RLS in a four-week randomized clinical trial. The diagnosis of RLS was made using the criteria of the International Restless Legs Study Group. Each subject completed three questionnaires: IRLS questionnaire, Pittsburgh Sleep Quality Index and Epworth sleepiness scale. After four weeks of washout period for previous treatments for RLS, subjects were randomly assigned to four weeks of gabapentin (200 mg) or levodopa-c (110 mg). After four weeks of therapy, the questionnaires administered at the outset of the study were re-administered. Both drugs were found effective for the management of RLS. But, the effect of gabapentin was more significant. Gabapentin significantly improved the IRLS total score (change from baseline to post-treatment ≈-17) compared with levodopa-c (change from baseline to post-treatment ≈-13) (P: 0.016). Regarding sleep parameters, levodopa improved sleep quality, sleep latency and sleep duration (P <0.0001). Gabapentin was also effective with respect to sleep parameters (P <0.0001). Our study shows that gabapentin is a safe effective therapy for RLS among hemodialysis patients. This medication may be considered as an alternative or additive treatment to current therapeutic remedies for hemodialysis patients with RLS.

How to cite this article:
Razazian N, Azimi H, Heidarnejadian J, Afshari D, Ghadami MR. Gabapentin versus levodopa-c for the treatment of restless legs syndrome in hemodialysis patients: A randomized clinical trial. Saudi J Kidney Dis Transpl 2015;26:271-8

How to cite this URL:
Razazian N, Azimi H, Heidarnejadian J, Afshari D, Ghadami MR. Gabapentin versus levodopa-c for the treatment of restless legs syndrome in hemodialysis patients: A randomized clinical trial. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2019 Nov 12];26:271-8. Available from: http://www.sjkdt.org/text.asp?2015/26/2/271/152417

   Introduction Top


Restless legs syndrome (RLS) is a neurological disorder characterized by a nocturnal urge to move the legs and is accompanied by uncomfortable feelings deep inside the legs. [1],[2] The symptoms get worse at rest or lying down and improve with movement, and are worse in the evening or at night than during the day. [3] Thus, RLS symptoms may delay sleep onset, reduce sleep efficiency and cause multiple awakenings, resulting in significant sleep disturbance for patients. [4],[5],[6]

RLS is frequent in some clinical conditions including iron deficiency, diabetes mellitus, peripheral neuropathy and renal failure. [7],[8],[10] RLS takes special attention in hemodialysis patients, and it is frequently reported in those patients who often complain about poorer quality of life, lower sleep quality, higher incidence of insomnia and increased levels of depresssion. [5],[11] RLS is an important cause of sleep disturbance that occurs in 5-15% of the normal population, whereas it is reported to vary from 6-60% among dialysis patients. [12],[13],[14],[15] Although sleep disorders have been frequently described in renal diseases, RLS remains under diagnosed and under treated.

Several therapeutic options have been suggested for the treatment of RLS in hemodialysis patients; however, none of these treatments are conclusively effective and some of them have serious side-effects. [13],[16],[17] The complex and not fully illustrated pathogenesis of RLS in hemodialysis patients is one of the main difficulties in the way of finding more effective and safer treatments for this disorder. [18]

Dopaminergic agents such as levodopa are the drugs of first choice in treating RLS. [19],[20],[21] Recently, gabapentin, an analogue of gamma-aminobutyric acid (GABA), has been shown to improve sensorimotor symptoms in RLS. [22] Gabapentin was associated with reduced symptoms in all rating scales and 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). [23]

Therefore, in the present study, the efficacy of treatment with either gabapentin or levodopa-c (Levodopa/Carbidopa) in hemodialysis patients with RLS was evaluated in a four-week randomized clinical trial.


   Materials and Methods Top


We conducted a randomized clinical trial using four weeks of gabapentin or levodopa-c therapy to treat RLS symptoms in hemodialysis patients. The study was approved by the ethics committee of the Kermanshah University of Medical Sciences and registered under code IRCT201112078323N1 in the Iranian Center of Clinical Trials (IRCT.ir). Informed consent was obtained from all participants. At the beginning of the study, hemodialysis patients from the Imam Reza Hospital, Kermanshah, Iran, were administered a questionnaire regarding symptoms of RLS. The criteria developed by the International RLS Study Group served as a guideline. [24] Minimum criteria include the presence of four clinical characteristics: (1) desire to move the limbs, in association with paresthesias and/or dysesthesias; (2) motor restlessness; (3) symptoms worse or exclusively occurring at rest partially and temporarily relieved by activity; and (4) symptoms worse in the evening or at night. The survey was based on a three-point ordinal scale from zero (never) to two (constantly).

Additional to the IRLS questionnaire, the evaluation tools included the Pittsburgh Sleep Quality Index (PSQI) and the Epworth sleepiness scale (ESS). The PSQI assesses sleep quality by measuring subjective sleep quality in the preceding one-month period. It comprises of 19 self-rated questions and five questions rated by a bed partner or roommate. The 19 items are grouped into seven component scores: Sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication and daytime dysfunction. The PSQI score (range, 0-21) is calculated by summing the component scores, whereby a higher score indicates worse sleep condition. A global PSQI score of five has been suggested to distinguish poor (PSQI >5) from good sleepers (PSQI <5), with diagnostic sensitivity of 100% and specificity of 93%. Overall, the Cronbach's alfa coefficient was 0.89. [25] The ESS is a self-administered, eight-item questionnaire that has adequately measured daytime sleepiness. Items address daily lifestyle activities and the respondent is asked to rate their likelihood of dozing in each situation, from "would never doze" (0) to "high chance of dozing" (3). The ESS provides a cumulative score between 0 and 24, with higher numbers indicating greater daytime sleepiness. [26]

Patients eligible for the treatment phase of the study had presence of all four characteristics with a minimum score of 10, minimum time of hemodialysis of three months, age more than 15 years and no evidence of other cause on neurological examination. Exclusion criteria included treatment with psychotropic agents during the recent four weeks, presence of another neurological disease comorbid with ESRD (such as CVA, MS, etc.), iron deficiency and pregnancy. Other recorded variables were hemoglobin, iron, ferritin and TIBC. These values are routinely obtained among patients on hemodialysis. After a washout phase of four weeks for previous treatments for RLS, subjects consenting to the protocol were randomly assigned four weeks of gabapentin or levodopa-c (Levodopa/Carbidopa). Gabapentin (200 mg) was administered three times weekly at the end of hemodialysis, 2 h before night bedtime. Levodopa-c (110 mg) was given in a single dose 2 h before night bedtime.

The research team performing the measurements and patients were masked to treatment assignment. After four weeks of therapy, the questionnaires administered at the outset of the study were re-administered. The questionnaires were explained by the study coordinator and completed by the patient during a dialysis session, with assistance provided to the patient if requested. Also, questions regarding adverse effects were asked as a part of nursing assessment before each dialysis administration.

In order to detect a mean difference of four scores in the reduction of RLS scores, a minimum sample size of 32 patients for each group was calculated, with an expected standard deviation of less than five scores, an alfa of 0.05 and a power of 0.90.

Scores from the questionnaire were tabulated and Student's t -test and chi square test were used to compare the results using SPSS v. 16.0, and P-values less than 0.05 were considered statistically significant.


   Results Top


From April 2011 through June 2012, 87 patients were identified (total population, 240 patients) with severe RLS (IRLS greater than 10). During the course of the study period, two patients dropped out during the study secondary to somnolence and lethargy. These patients were administered gabapentin when the symptoms developed. One patient died because of myocardial infarction. One patient failed to follow-up due to migration. One of the patients had allergy to levodopa-c during the first week and dropped out of the study. Despite these lapses in compliance, 82 patients continued to participate. [Figure 1] summarizes the trial profile. Patient demographics are listed in [Table 1]. Baseline characteristics of the study participants, including sex, age and duration of dialysis, were similar between the study treatment groups. Laboratory assessments including Hb, ferritin, iron and TIBC were also similar between the study groups [Table 1].
Figure 1: Trial profile.

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Table 1: Demographic and baseline sleep characteristics of patients in the two study groups.

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Baseline IRLS scores and sleep parameters were comparable between treatment groups [Table 2]. Both drugs were found to be effective for the management of RLS (paired t test for each group: P <0.0001). But, when we compared the two drugs for severity of RLS symptom relief, the effect of gabapentin was more significant (P: 0.016). Gabapentin significantly improved the IRLS total score (baseline: 27.8 ± 4.6; post-treatment: 10.4 ± 5.7; change from baseline to post-treatment ≈ -17) compared with levodopa-c (baseline: 27.6 ± 4.4; post-treatment: 14.2 ± 7.6; change from baseline to post-treatment: –13).
Table 2: Post-treatment IRS scores and sleep characteristics in the two study groups.

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Regarding sleep parameters, both gabapentin and levodopa-c improved sleep quality, sleep latency and sleep duration compared with baseline (paired t test for each group: P <0.05).

Additionally, when we compared the scores between levodopa and gabapentin, gabapentin was significantly superior to levodopa for sleep latency (P: 0.001), sleep disturbance (P <0.0001) and sleep quality (P <0.0001) [Table 2].

When we compared the ESS score between groups at the end of treatment time, there were no significant differences between the two groups (P: 0.116), but gabapentin significantly improved ESS with greater improvements in mean change from baseline to post-treatment (baseline: 12.2 ± 5.6; post-treatment: 3.9 ± 2.8; change from baseline to post-treatment ≈ -8.3) compared with levodopa-c (baseline: 10.6 ± 5.2; post-treatment: 5.2 ± 4.4; change from baseline to post-treatment: -5.4; P <0.0001).

There were no significant side-effects, except for daytime sleepiness and hypotention. Six patients in the gabapentin group and two patients in the levodopa group complained of daytime sleepiness (P: 0.265). Also, transient hypotension occurred in two patients in the levodopa group during the first week of the study period.


   Discussion Top


RLS is a common cause of discomfort and morbidity among hemodialysis patients. The pathophysiology of RLS in hemodialysis patients is complex and not well understood. Many studies suggested that dopaminergic dysfunction has a major role in the pathophysiology of this disorder. [27],[28] Dopaminergic functional insufficiency in RLS is due to the decreased synthesis of dopamine or its recaetors in certain areas of the central nervous system. Clinical evidence suggested that RLS symptoms are worse at night when dopamine levels fall. Also, RLS improves with use of dopaminergic medications and is exacerbated with use of dopamine blockers. [28]

We assessed the severity of RLS and sleep quality index among the patients with RLS and compared the efficacy of levodopa-c (a well-known first choice drug) and gabapentin (an anticonvulsant drug). The European guidelines on management of RLS considered gabapentin in Level A recommendations for the short-term treatment for RLS. [29] However, an American Academy of Sleep Medicine Clinical Practice Guideline for the treatment of RLS and periodic limb movement disorder in adults considered levodopa in the GUIDELINE level of recommendation and gabapentin in the OPTION level of recommendation. [30]

Our study demonstrates the superior efficacy of gabapentin (200 mg daily) compared with levodopa-c. This dose of 200 mg of gabapentin was selected based on previous RCT studies that reported that 200-300 mg gabapentin after a hemodialysis session significantly improved RLS symptoms. [31],[32] Moreover, treatment with gabapentin was found to be safe and without serious side-effects in the short-term. The results of this four-week study of gabapentin in the treatment of moderate-tosevere RLS confirm the efficacy and tolera-bility as reported by Micozkadioglu et al in a study of gabapentin 200 mg versus levodopa. [31] In our study, mean reductions in the IRLS total score from baseline with gabapentin versus levodopa (-17 and -13) were comparable with those reported by Micozkadioglu et al (-14 and -7). The reductions in IRLS total score observed in our study are comparable with those reported for dopamine agonists that are currently approved for the treatment of RLS. [33],[34],[35],[36],[37]

Studies have shown the benefit of gabapentin administration in the treatment of RLS, possibly through its interaction with the D2 receptors. A study by Mellick et al showed that patients with RLS treated with gabapentin responded to treatment and that side-effects proved transient. [38] But, these results contrast with the findings from a study of gabapentin by Walters et al that reported a non-significant mean reduction from baseline in the IRLS total score (-9.1) compared with placebo. [39] In the present study, gabapentin significantly improved the mean IRLS total score compared with levodopa-c (-17 versus -13; P: 0.016). Therefore, it is unlikely that the duration of treatment accounted for the differences in outcomes between these studies.

Sleep problem is a main problem for RLS patients. In fact, although sleep disturbances are not part of the RLS diagnostic criteria, patients often report sleep disturbance due to RLS symptoms. [40],[41] In the present study, patients in the levodopa-c group reported significant sleep disturbance on the PSQ and ESS compared with gabapentin. Although both levodopa and gabapentin improved sleep quality, sleep latency and sleep duration, when we compared the two drugs, gabapentin was found to be statistically superior with respect to sleep quality, sleep latency and sleep disturbance. Gabapentin demonstrated significant improvements on daily function and on the sleep disturbance, sleep quantity and sleep adequacy and all PSQ and ESS items four weeks after treatment initiation. These improvements in sleep outcomes were consistent with those reported for gabapentin 200 mg in the study by Micozkadioglu et al. [27]

In the study of Micozkadioglu et al, assessment of quality of life showed that administration of levodopa only improved body pain and that patients were complaining about incompatible social activities because of RLS symptoms. On the other hand, gabapentin improved body pain as well as general health and social activities. The authors concluded that this effect was possibly because of the high effectiveness and long half-life of gabapentin. [27]

Although there was no significant difference regarding side-effects between the two groups, it should be noted that daytime sleepiness was more common in the gabapentin-treated patients in our study. It was a side-effect, but may be an additional advantage of gabapentin for these patients.

In summary, gabapentin is a safe and effective therapy for RLS among hemodialysis patients. With an increase of RLS randomized clinical trials, the low sample size is the main limitation to main studies and the extrapolation of its results. In this study, we attempt to assess more patients compared with previous studies. In conclusion, our study shows that gabapentin (200 mg daily) is a safe and effective treatment for RLS in hemodialysis patients in the short term. Therapy with gabapentin in hemodialysis patients is optimized because it can be administered in the hemodialysis unit at the completion of a hemodialysis session. Thus, this medication may be considered as an alternative or additive treatment to current therapeutic remedies for this conundrum. However, this study is limited by its short duration. There is a need for double-blinded, randomized studies comparing long-acting levodopa and other dopaminergic agents with gabapentin and to show the efficacy of gabapentin in hemodialysis patients with RLS.

Conflict of interest: None

 
   References Top

1.
Merlino G, Gigli GL. Sleep-related movement disorders. Neurol Sci 2012;33:491-513.  Back to cited text no. 1
    
2.
Merlino G, Serafini A, Robiony F, Valente M, Gigli GL. Restless legs syndrome: Differential diagnosis and management with rotigotine. Neuropsychiatr Dis Treat 2009;5:67-80.  Back to cited text no. 2
    
3.
Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J; Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group. Restless Legs Syndrome: Diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101-19.  Back to cited text no. 3
    
4.
Hening WA. Subjective and objective criteria in the diagnosis of the restless legs syndrome. Sleep Med 2004;5:285-92.  Back to cited text no. 4
    
5.
Rijsman RM, de Weerd AW, Stam CJ, Kerkhof GA, Rosman JB. Periodic limb movement disorder and restless legs syndrome in dialysis patients. Nephrology (Carlton) 2004;9: 353-61.  Back to cited text no. 5
    
6.
Giannaki CD, Sakkas GK, Hadjigeorgiou GM, et al. Non-pharmacological management of periodic limb movements during hemodialysis session in patients with uremic restless legs syndrome. ASAIO J 2010;56:538-42.  Back to cited text no. 6
    
7.
Zucconi M, Ferini-Strambi L. Epidemiology and clinical findings of restless legs syndrome. Sleep Med 2004;5:293-9.  Back to cited text no. 7
    
8.
Nineb A, Rosso C, Dumurgier J, Nordine T, Lefaucheur JP, Creange A. Restless legs syndrome is frequently overlooked in patients being evaluated for polyneuropathies. Eur J Neurol 2007;14:788-92.  Back to cited text no. 8
    
9.
Bastos JP, Sousa RB, Nepomuceno LA, et al. Sleep disturbances in patients on maintenance hemodialysis: Role of dialysis shift. Rev Assoc Med Bras 2007;53:492-6.  Back to cited text no. 9
    
10.
Lopes LA, Lins CM, Adeodato VG, et al. Restless legs syndrome and quality of sleep in type 2 diabetes. Diabetes Care 2005;28:2633-6.  Back to cited text no. 10
    
11.
Mucsi I, Molnar MZ, Ambrus C, et al. Restless legs syndrome, insomnia and quality of life in patients on maintenance dialysis. Nephrol Dial Transplant 2005;20:571-7.  Back to cited text no. 11
    
12.
Siddiqui S, Kavanagh D, Traynor J, Mak M, Deighan C, Geddes C. Risk factors for restless legs syndrome in dialysis patients. Nephron Clin Pract 2005;101:c155-60.  Back to cited text no. 12
    
13.
Kavanagh D, Siddiqui S, Geddes CC. Restless legs syndrome in patients on dialysis. Am J Kidney Dis 2004;43:763-71.  Back to cited text no. 13
    
14.
Walker S, Fine A, Kryger MH. Sleep complaints are common in a dialysis unit. Am J Kidney Dis 1995;26:751-6.  Back to cited text no. 14
    
15.
Araujo SM, de Bruin VM, Nepomuceno LA. Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities. Sleep Med 2010;11:785-90.  Back to cited text no. 15
    
16.
de Oliveira MM, Conti CF, Valbuza JS, de Carvalho LB, Do Prado GF. The pharmacological treatment for uremic restless legs syndrome: Evidence-based review. Mov Disord 2010;25:1335-42.  Back to cited text no. 16
    
17.
Molnar MZ, Novak M, Mucsi I. Management of restless legs syndrome in patients on dialysis. Drugs 2006;66:607-24.  Back to cited text no. 17
    
18.
Sagheb MM, Dormanesh B, Fallahzadeh MK. Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: A randomized, double-blind, placebo-controlled trial. Sleep Med 2012;13:542-5.  Back to cited text no. 18
    
19.
Clavadetscher SC, Gugger M, Bassetti CL. Restless legs syndrome: Clinical experience with long-term treatment. Sleep Med 2004; 5:495-500.  Back to cited text no. 19
    
20.
Scholz H, Trenkwalder C, Kohnen R, Riemann D, Kriston L, Hornyak M. Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev 2011;3:CD006009.  Back to cited text no. 20
    
21.
Standards of Practice Committee of the American Academy of Sleep Medicine. Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder. Sleep 2004;27:557-9.  Back to cited text no. 21
    
22.
Happe S, Sauter C, Klösch G, Saletu B, Zeitlhofer J. Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 2003;48:82-6.  Back to cited text no. 22
    
23.
Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: A double-blind, cross-over study. Neurology 2002;59:1573-9.  Back to cited text no. 23
    
24.
Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. Restless legs syndrome: Diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003; 4:101-19.  Back to cited text no. 24
    
25.
Farrahi Moghaddam J, Nakhaee N, Sheibani V, Garrusi B, Amirkafi A. Reliability and validity of the Persian version of the Pittsburgh Sleep Quality Index (PSQI-P). Sleep Breath 2012;16:79-82.  Back to cited text no. 25
    
26.
Sadeghniiat Haghighi K, Montazeri A. The Epworth Sleepiness Scale: Translation and validation study of the Iranian version. Sleep Breath 2013;17:419-26.  Back to cited text no. 26
    
27.
Winkelman JW. Considering the causes of RLS. Eur J Neurol 2006;13(Suppl 3):8-14.  Back to cited text no. 27
    
28.
Allen RP. Controversies and challenges in defining the etiology and pathophysiology of restless legs syndrome. Am J Med 2007;120: S13-21.  Back to cited text no. 28
    
29.
Garcia-Borreguero D, Ferini-Strambi L, Kohnen R, et al. European guidelines on management of restless legs syndrome: Report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society. Eur J Neurol 2012;19:1385-96.  Back to cited text no. 29
    
30.
Aurora RN, Kristo DA, Bista SR, et al; American Academy of Sleep Medicine. The treatment of restless legs syndrome and periodic limb movement disorder in adults-an update for 2012: Practice parameters with an evidence-based systematic review and meta-analyses: An American Academy of Sleep Medicine Clinical Practice Guideline. Sleep 2012;35:1039-62.  Back to cited text no. 30
    
31.
Micozkadioglu H, Ozdemir FN, Kut A, Sezer S, Saatci U, Haberal M. Gabapentin versus levodopa for the treatment of Restless Legs Syndrome in hemodialysis patients: An open-label study. Ren Fail 2004;26:393-7.  Back to cited text no. 31
    
32.
Thorp ML, Morris CD, Bagby SP. A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis 2001;38:104-8.  Back to cited text no. 32
    
33.
Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY. Ropinirole in the treatment of patients with restless legs syndrome: A US-based randomized, doubleblind, placebo-controlled clinical trial. Mayo Clin Proc 2006;81:17-27.  Back to cited text no. 33
    
34.
Ferini-Strambi L, Aarskog D, Partinen M, et al. Effect of pramipexole on RLS symptoms and sleep: A randomized, double-blind, placebo-controlled trial. Sleep Med 2008;9:874-81.  Back to cited text no. 34
    
35.
Benes H, Kurella B, Kummer J, Kazenwadel J, Selzer R, Kohnen R. Rapid onset of action of levodopa in restless legs syndrome: A double-blind, randomized, multicenter, crossover trial. Sleep 1999;22:1073-81.  Back to cited text no. 35
    
36.
Saletu M, Anderer P, Högl B, et al. Acute double-blind, placebo-controlled sleep laboratory and clinical follow-up studies with a combination treatment of rr-L-dopa and sr-L-dopa in restless legs syndrome. J Neural Transm 2003;110:611-26.  Back to cited text no. 36
    
37.
Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology 2006;67:1034-9.  Back to cited text no. 37
    
38.
Mellick GA, Mellick LB. Management of restless legs syndrome with gabapentin (Neurontin). Sleep 1996;19:224-6.  Back to cited text no. 38
    
39.
Walters AS, Ondo WG, Kushida CA, et al. Gabapentin enacarbil in restless legs syndrome: A phase 2b, 2-week, randomized, double-blind, placebo-controlled trial. Clin Neuropharmacol 2009;32:311-20.  Back to cited text no. 39
    
40.
Kushida CA, Allen RP, Atkinson MJ. Modeling the causal relationships between symptoms associated with restless legs syndrome and the patient-reported impact of RLS. Sleep Med 2004;5:485-8.   Back to cited text no. 40
    
41.
Hening W, Walters AS, Allen RP, Montplaisir J, Myers A, Ferini-Strambi L. Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: The REST (RLS epidemiology, symptoms, and treatment) primary care study. Sleep Med 2004;5:237-46.  Back to cited text no. 41
    

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Correspondence Address:
Dr. Mohammad Rasoul Ghadami
Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah
Iran
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DOI: 10.4103/1319-2442.152417

PMID: 25758874

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