Strategies for the Treatment of Restless Legs Syndrome

Neurotherapeutics

Volumn 9, Issue 4, 2012, Pages 776-790

  Buchfuhrer, Mark J ^a,b  

^a Solo Clinical Practice   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Anticonvulsants; Augmentation; Dopamine agonists; Gabapentin enacarbil; Methadone; Opioids; Pramipexole; Restless legs syndrome; Ropinirole; Rotigotine

Indexed keywords

CANNABIS; CARBAMAZEPINE; CODEINE; DEXTROPROPOXYPHENE; DIHYDROCODEINE; ESZOPICLONE; ETIRACETAM; FENTANYL; GABAPENTIN; GABAPENTIN ENACARBIL; HYDROCODONE; LAMOTRIGINE; LEVODOPA; LEVORPHANOL; METHADONE; MORPHINE; OPIATE; OXCARBAZEPINE; OXYCODONE; PENTAZOCINE; PETHIDINE; PRAMIPEXOLE; PREGABALIN; ROPINIROLE; ROTIGOTINE; TILIDINE; TRAMADOL; ZOLPIDEM;

APPLICATION SITE REACTION; CLINICAL DECISION MAKING; CONSTIPATION; CONTRACEPTION; DISEASE EXACERBATION; DISEASE SEVERITY; DIZZINESS; DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG WITHDRAWAL; EXERCISE; GOVERNMENT; HEALTH CARE AVAILABILITY; HUMAN; HYPOTENSION; IMPULSE CONTROL DISORDER; INSOMNIA; IRON THERAPY; LOW DRUG DOSE; MONOTHERAPY; MORBIDITY; NAUSEA; PHYSICAL ACTIVITY; PRIORITY JOURNAL; RESPIRATION DEPRESSION; RESTLESS LEGS SYNDROME; REVIEW; SEDATION; SIDE EFFECT; SUICIDAL IDEATION;

ANALGESICS, OPIOID; ANTICONVULSANTS; DOPAMINE AGONISTS; HUMANS; RESTLESS LEGS SYNDROME;

EID: 84868013734     PISSN: 19337213     EISSN: 18787479     Source Type: Journal    
DOI: 10.1007/s13311-012-0139-4     Document Type: Review

References (150)

1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir 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: 101-119.
2. Montplaisir J, Boucher S, Poirier G, Lavigne G, Lapierre O, Lespérance P. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov Disord 1997; 12: 61-65.
3. Dorsey CM, Lukas SE, Cunningham SL. Fluoxetine-induced sleep disturbance in depressed patients. Neuropsychopharmacology 1996; 14: 437-442.
4. Salín-Pascual RJ, Galicia-Polo L, Drucker-Colin R. Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 1997; 58: 348-350.
5. Allen RP, Labuda MC, Becker PM, Earley CJ. Family history study of the restless legs syndrome. Sleep Med 2002; 3: S3-S7.
6. Innes KE, Selfe TK, Agarwal P. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med 2011; 12: 623-634.
7. Sevim S, Dogu O, Camdeviren H, et al. Unexpectedly low prevalence and unusual characteristics of RLS in Mersin, Turkey. Neurology 2003; 61: 1562-1569.
8. Taşdemir M, Erdoǧan H, Börü UT, Dilaver E, Kumaş A. Epidemiology of restless legs syndrome in Turkish adults on the western Black Sea coast of Turkey: a door-to-door study in a rural area. Sleep Med 2010; 11: 82-86.
9. Kim KW, Yoon IY, Chung S, et al. Prevalence, comorbidities and risk factors of restless legs syndrome in the Korean elderly population - results from the Korean Longitudinal Study on Health and Aging. J Sleep Res 2010; 19(1 Pt 1): 87-92.
10. Chen NH, Chuang LP, Yang CT, et al. The prevalence of restless legs syndrome in Taiwanese adults. Psychiatry Clin Neurosci 2010; 64: 170-178.
11. Cho YW, Shin WC, Yun CH, et al. Epidemiology of restless legs syndrome in Korean adults. Sleep 2008; 31: 219-223.
12. Kim J, Choi C, Shin K, et al. Prevalence of restless legs syndrome and associated factors in the Korean adult population: the Korean Health and Genome Study. Psychiatry Clin Neurosci 2005; 59: 350-353.
13. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005; 165: 1286-1292.
14. Berger K, von Eckardstein A, Trenkwalder C, Rothdach A, Junker R, Weiland SK. Iron metabolism and the risk of restless legs syndrome in an elderly general population - the MEMO Study. J Neurol 2002; 249: 1195-1199.
15. Berger K, Luedemann J, Trenkwalder C, John U, Kessler C. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med 2004; 164: 196-202.
16. Ohayon MM, Roth T. Prevalence of restless legs syndrome and periodic limb movement disorder in the general population. J Psychosom Res 2002; 53: 547-554.
17. Högl B, Kiechl S, Willeit J, et al. Restless legs syndrome: a community-based study of prevalence, severity, and risk factors. Neurology 2005; 64: 1920-1924.
18. Walters AS, Hickey K, Maltzman J, et al. A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey. Neurology 1996; 46: 92-95.
19. Lavigne GJ, Montplaisir JY. Restless legs syndrome and sleep bruxism: prevalence and association among Canadians. Sleep 1994; 17: 739-743.
20. Raizen DM, Wu MN. Genome-wide association studies of sleep disorders. Chest 2011; 139: 446-452.
21. O'Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing 1994; 23: 200-203.
22. Sun ER, Chen CA, Ho G, et al. Iron and the restless legs syndrome. Sleep 1998; 21: 371-377.
23. Goodman JD, Brodie C, Ayida GA. Restless leg syndrome in pregnancy. Br Med J 1988; 297: 1101-1102.
24. Lee KA, Zaffke ME, Baratte-Beebe K. Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron. J Womens Health Gend Based Med 2001; 10: 335-341.
25. Manconi M, Govoni V, De Vito A, et al. Pregnancy as a risk factor for restless legs syndrome. Sleep Medicine 2004; 5: 305-308.
26. Pantaleo NP, Hening WA, Allen RP, Earley CJ. Pregnancy accounts for most of the gender difference in prevalence of familial RLS. Sleep Med 2010; 11: 310-313.
27. Walker S, Fine A, Kryger MH. Sleep complaints are common in a dialysis unit. Am J Kidney Dis 1995; 26: 751-766.
28. Winkelman JW, Chertow GM, Lazarus JM. Restless legs syndrome in end-stage renal disease. Am J Kidney Dis 1996; 28: 372-378.
29. Gigli GL, Adorati M, Dolso P, et al. Restless legs syndrome in end-stage renal disease. Sleep Med 2004; 5: 309-315.
30. Tan EK, Lum SY, Wong MC. Restless legs syndrome in Parkinson's disease. J Neurol Sci 2002; 196: 33-36.
31. Krishnan PR, Bhatia M, Behari M. Restless legs syndrome in Parkinson's disease: a case-controlled study. Mov Disord 2003; 18: 181-185.
32. Nomura T, Inoue Y, Miyake M, Yasui K, Nakashima K. Prevalence and clinical characteristics of restless legs syndrome in Japanese patients with Parkinson's disease. Mov Disord 2006; 21: 380-384.
33. Gao X, Schwarzschild MA, O'Reilly EJ, Wang H, Ascherio A. Restless legs syndrome and Parkinson's disease in men. Mov Disord 2010; 25: 2654-2657.
34. Manconi M, Ferini-Strambi L, Filippi M, et. al. Multicenter Case-Control Study on Restless Legs Syndrome in Multiple Sclerosis: the REMS Study. Sleep 2008; 31: 944-952.
35. Abele M, Burk K, Laccone F, Dichgans J, Klockgether T. Restless legs syndrome in spinocerebellar ataxia types 1, 2, and 3. J Neurol 2001; 248: 311-314.
36. Polydefkis M, Allen RP, Hauer P, Earley CJ, Griffin JW, McArthur JC. Subclinical sensory neuropathy in late-onset restless legs syndrome. Neurology 2000; 55: 1115-1121.
37. Merlino G, Fratticci L, Valente M, et al. Association of restless legs syndrome in type 2 diabetes: a case-control study. Sleep 2007; 30: 866-871.
38. Gemignani F, Brindani F, Vitetta F, Marbini A, Calzetti S. Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy. J Peripher Nerv Syst 2007; 12: 50-53.
39. Boentert M, Dziewas R, Heidbreder A, et al. Fatigue, reduced sleep quality and restless legs syndrome in Charcot-Marie-Tooth disease: a web-based survey. J Neurol 2010; 257: 646-652.
40. Ondo WG, Lai D. Association between restless legs syndrome and essential tremor. Mov Disord 2006; 21: 515-518.
41. Brown LK, Heffner JE, Obbens EA. Transverse myelitis associated with restless legs syndrome and periodic movements of sleep responsive to an oral dopaminergic agent but not to intrathecal baclofen. Sleep 2000; 23: 591-594.
42. Rutkove SB, Matheson JK, Logigian EL. Restless legs syndrome in patients with polyneuropathy. Muscle Nerve 1996; 19: 670-672.
43. Gemignani F, Brindani F, Negrotti A, Vitetta F, Alfieri S, Marbini A. Restless legs syndrome and polyneuropathy. Mov Disord 2006; 21: 1254-1257.
44. Silber MH, Ehrenberg BL, Allen RP, et al; Medical Advisory Board of the Restless Legs Syndrome Foundation. An algorithm for the management of restless legs syndrome. Mayo Clin Proc 2004; 79: 916-922.
45. Hening WA. Current guidelines and standards of practice for restless legs syndrome. Am J Med 2007; 120(1 suppl 1): S22-S27.
46. Oertel WH, Trenkwalder C, Zucconi M, et al. State of the art in restless legs syndrome therapy: practice recommendations for treating restless legs syndrome. Mov Disord 2007; 22(suppl 18): S466-S475.
47. Garcia-Borreguero D, Stillman P, Benes H, et al. Algorithms for the diagnosis and treatment of restless legs syndrome in primary care. BMC Neurol 2011; 11: 28.
48. Lutz EG, Restless legs, anxiety, and caffeinism. J Clin Psychiatry 1978; 39: 693-698.
49. Mountifield JA. Restless legs syndrome relieved by cessation of smoking. Can Med Assoc J 1985; 133: 426-427.
50. Lavigne GJ, Lobbezoo F, Rompre PH, et al. Cigarette smoking as a risk factor or and exacerbating factor for restless legs syndrome and sleep bruxism. Sleep 1997; 20: 290-293.
51. Phillips B, Young T, Finn L, et al. Epidemiology of restless legs syndrome in adults. Arch Intern Med 2000; 160: 2137-2141.
52. Berger K, Luedemann J, Trenkwalder C, et al. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med 2004; 164: 196-202.
53. Roth T, Roehrs T, Zorick F, Conway W. Pharmacological effects of sedative - hypnotics, narcotics analgesics, and alcohol during sleep. Med Clin North Am 1985; 69: 1281-1288.
54. Rouhani S, Tran G, Leplaindeur F, et al. EEG effects on a single low dose of ethanol on afternoon sleep in the nonalcohol-dependent adult. Alcohol 1989; xx: 687-690.
55. Montplaisir J, Lorrain D, Godabout R. Restless legs syndrome and periodic leg movements in sleep: the primary role of dopaminergic mechanism. Eur Neruol 1991; 31: 41-43.
56. Drotts DL, Vinson DR. Prochlorperazine induces akathisia in emergency patients. Ann Emerg Med 1999; 34: 469-475.
57. 3 receptor antagonist, on dopamine and serotonin metabolism in mesolimbic and nigrostriatal neurons. Eur J Pharmocol 1989; 169: 321-324.
58. Wetter TC, Stiasny K, Winkelmann J, et al. A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology 1999; 52: 944-950.
59. Sanz-Fuentenebro FJ, Huidobro A, Tejada-Rivas A. Restless legs syndrome and paroxetine. Ann Psychiatr Scand 1996; P94: 482-484.
60. Hargrave R, Beckley DJ. Restless leg syndrome exacerbated by sertraline. Psychosomatics 1998; 2: 177-178.
61. Teive HA, de Quadros A, Barros FC, Werneck LC. Worsening of autosomal dominant restless legs syndrome after use of mirtazapine: case report. Arq Neuropsiquiatr 2002; 60: 1025-1029.
62. Bahk WM, Pae CU, Chae JH, Kim KS. Mirtazapine may have the propensity for developing a restless legs syndrome? A case report. Psychiatry Clin Neurosci 2002; 56: 209-210.
63. Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R. Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 1997; 58: 248-350.
64. Rottach KG, Schaner BM, Kirch MH, et al. Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr Res 2008; 43: 70-75.
65. Hoque R, Chesson AL Jr. Pharmacologically induced/exacerbated restless legs syndrome, periodic limb movements of sleep, and rem behavior disorder/rem sleep without atonia: literature review, qualitative scoring, and comparative analysis. J Clin Sleep Med 2010; 6: 79-83.
66. Garvey MJ, Tolefson GD. Occurrence of myoclonus in patients treated with cyclic antidepressants. Arch Gen Psychiatr 1987; 44: 429-474.
67. Lee JJ, Erdos J, Wilkosz MF, LaPlante R, Wagoner B. Bupropion as a possible treatment option for restless legs syndrome. Ann Pharmacother 2009; 43: 370-4.
68. Kim SW, Shin IS, Kim JM, Yang SJ, Shin HY, Yoon JS. Bupropion may improve restless legs syndrome: a report of three cases. Clin Neuropharmacol 2005; 28: 298-301.
69. Bayard M, Bailey B, Acharya D, et al. Bupropion and restless legs syndrome: a randomized controlled trial. Am Board Fam Med 2011; 24: 422-428.
70. Chiodo LA. Dopmine-containing neurons in the mammalian central nervous system: electrophysiology and pharmacology. Neurosci Biobehav Rev 1998; 12: 49-91.
71. Walters AS, Hening W, Rubinstein M, et al. A clinical and polysomnographic comparison of neuroleptic-induced akathisia and the idiopathic restless legs syndrome. Sleep 1991; 14: 339-45.
72. Kraus T, Schuld A, Pollmacher T. Perodic leg movements in sleep and restless legs syndrome probably caused olanzapine. J Clin Psychopharmocol 1999: 19: 478-479.
73. Wetter TC, Brunner J, Bronisch T. Restless legs syndrome probably induced by risperidone treatment. Pharmacopsychiatry 2002; 35: 109-111.
74. Terao T, Terao M, Yoshimura R, Kazuhiko A. Restless legs syndrome induced by lithium. Biol Psychiatry 1991: 30: 1167-1170.
75. Ekbom K. Restless legs: a clinical study. Acta Med Scand 1945; 121(supplement 158): 1-123.
76. Ekbom KA. Restless legs syndrome. Neurology 1960; 10: 868-873.
77. Nordlander NB. Therapy in restless legs. Acta Med Scand 1953; 145: 453-457.
78. Parrow A, Werner I. The treatment of restless legs. Acta Med Scand 1966; 100: 401-407.
79. Wang J, O'Reilly B, Venkataraman R, Mysliwiec V, Mysliwiec A. Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: a randomized, double-blind, placebo-controlled study. Sleep Med 2009; 10: 973-975.
80. Mohri I, Kato-Nishimura K, Kagitani-Shimono K, et al. Evaluation of oral iron treatment in pediatric restless legs syndrome (RLS). Sleep Med 2012; xx: xx-xx.
81. Davis BJ, Rajput A, Rajput ML, Aul EA, Eichhorn GR. A randomized, double-blind placebo-controlled trial of iron in restless legs syndrome. Eur Neurol 2000; 43: 70-75.
82. Trotti LM, Bhadriraju S, Becker LA. Iron for restless legs syndrome. Cochrane Database Syst Rev 2012; 5: CD007834.
83. Hening WA, Allen RP, Chokroverrty S, Earley CJ. Restless legs syndrome. Saunders 2009: 272-275.
84. Matthews WB. Treatment of the restless legs syndrome with clonazepam. Br Med J 1979; 1: 751.
85. Akpinar S. Treatment of restless legs syndrome with levodopa plus benserazide. Arch Neurol 1982; 39: 739.
86. Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep 1996; 19: 205-213.
87. Adler CH, Hauser RA, Sethi K, et al. Ropinirole for restless legs syndrome: a placebo-controlled crossover trial. Neurology 2004; 62: 1405-1407.
88. Allen R, Becker PM, Bogan R, et al. Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome. Sleep 2004; 27: 907-914.
89. Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Ropinirole in the treatment of restless legs syndrome: results from a 12-week, randomised, placebo-controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 2004; 75: 92-97.
90. Walters AS, Ondo WG, Dreykluft T, Grunstein R, Lee D, Sethi K. Ropinirole is effective in the treatment of restless legs syndrome. TREAT RLS 2: a 12-week, double-blind, randomized, parallel group, placebo-controlled study. Mov Disord 2004; 19: 1414-1423.
91. Bliwise DL, Freeman A, Ingram CD, Rye DB, Chakravorty S, Watts RL. Randomized, double-blind, placebo-controlled, short-term trial of ropinirole in restless legs syndrome. Sleep Med 2005; 6: 141-147.
92. Bogan RK, Fry JM, Schmidt MH, Carson SW, Ritchie SY. Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial. Mayo Clin Proc 2006; 81: 17-27.
93. Montplaisir J, Nicolas A, Denesle R, Gomez-Mancilla B. Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology 1999; 52: 938-943.
94. Partinen M, Hirvonen K, Jama L, et al. Efficacy and safety of pramipexole in idiopathic restless legs syndrome: a polysomnographic dose-finding study - the PRELUDE study. Sleep Med 2006; 7: 407-417.
95. Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology 2006; 67: 1034-1039.
96. Trenkwalder C, Stiasny-Kolster K, Kupsch A, Oertel WH, Koester J, Reess J. Controlled withdrawal of pramipexole after 6 months of open-label treatment in patients with restless legs syndrome. Mov Disord 2006; 21: 1404-1410.
97. Oertel WH, Stiasny-Kolster K, Bergtholdt B, et al. Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study). Mov Disord 2007; 22: 213-219.
98. Uitti RJ, Tanner CM, Rajput AH, Goetz CG, Klawans HL, Thiessen B. Hypersexuality with antiparkinsonian therapyClin Neuropharmacol 1989; 12: 375-383.
99. Molina JA, Sáinz-Artiga MJ, Fraile A, et al. Pathologic gambling in Parkinson's disease: a behavioral manifestation of pharmacologic treatment? Mov Disord 2000; 15: 869-872.
100. Tippmann-Peikert M, Park JG, Boeve BF, Shepard JW, Silber MH. Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists. Neurology 2007; 68: 301-303.
101. Stiasny-Kolster K, Kohnen R, Schollmayer E, Möller JC, Oertel WH. Rotigotine Sp 666 Study Group. Patch application of the dopamine agonist rotigotine to patients with moderate to advanced stages of restless legs syndrome: a double-blind, placebo-controlled pilot study. Mov Disord 2004; 19: 1432-1438.
102. Oertel WH, Benes H, Garcia-Borreguero D, et al; Rotigotine SP 709 Study Group. Efficacy of rotigotine transdermal system in severe restless legs syndrome: a randomized, double-blind, placebo-controlled, six-week dose-finding trial in Europe. Sleep Med 2008; 9: 228-239.
103. Trenkwalder C, Benes H, Poewe W, et al; SP790 Study Group. Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2008; 7: 595-604.
104. Hening WA, Allen RP, Ondo WG, et al; SP792 Study Group. Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States. Mov Disord 2010; 25: 1675-1683.
105. Högl B, Oertel WH, Stiasny-Kolster K, et al. Treatment of moderate to severe restless legs syndrome: 2-year safety and efficacy of rotigotine transdermal patch. BMC Neurol 2010; 10: 86.
106. Oertel W, Trenkwalder C, Beneš H, et al; SP710 study group. Long-term safety and efficacy of rotigotine transdermal patch for moderate-to-severe idiopathic restless legs syndrome: a 5-year open-label extension study. Lancet Neurol 2011; 10: 710-720.
107. Beneš H, García-Borreguero D, Ferini-Strambi L, Schollmayer E, Fichtner A, Kohnen R. Augmentation in the treatment of restless legs syndrome with transdermal rotigotine. Sleep Med 2012; xx: xx-xx.
108. Earley CJ, Allen RP. Restless legs syndrome augmentation associated with tramadol. Sleep Med 2006; 7: 592-593.
109. Vetrugno R, La Morgia C, D'Angelo R, et al. Augmentation of restless legs syndrome with long-term tramadol treatment. Mov Disord 2007; 22: 424-427.
110. Garcia-Borreguero D, Allen RP, Kohnen R, Hogl B. Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine - RLSSG consensus conference at the Max Planck Institute. Sleep Med 2007; 8: 520-530.
111. Silver N, Allen RP, Senerth J, Earley CJ. A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome. Sleep Med 2011; 12: 440-444.
112. Trenkwalder C, Högl B, Benes H, Kohnen R. Augmentation in restless legs syndrome is associated with low ferritin. Sleep Med 2008; 9: 572-574.
113. Frauscher B, Gschliesser V, Brandauer E, et al. The severity range of restless legs syndrome (RLS) and augmentation in a prospective patient cohort: association with ferritin levels. Sleep Med 2009; 10: 611-615.
114. Mellick GA, Mellick LB. Management of restless legs syndrome with gabapentin (Neurontin). Sleep 1996; 19: 224-246.
115. Adler CH. Treatment of restless legs syndrome with gabapentin. Clin Neuropharmacol 1997; 20: 148-151.
116. Happe S, Klösch G, Saletu B. Zeitlhofer Treatment of idiopathic restless legs syndrome (RLS) with gabapentin. J Neurology 2001; 57: 1717-1719.
117. 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: 1573-1579.
118. Happe S, Sauter C, Klösch G, Saletu B, Zeitlhofer J. Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 2003; 48: 82-86.
119. Saletu M, Anderer P, Saletu-Zyhlarz GM, et al. Comparative placebo-controlled polysomnographic and psychometric studies on the acute effects of gabapentin versus ropinirole in restless legs syndrome. J Neural Transm 2010; 117: 463-473.
120. 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: 104-108.
121. 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: 393-397.
122. Merlino G, Serafini A, Lorenzut S, Sommaro M, Gigli GL, Valente M. Gabapentin enacarbil in restless legs syndrome. Drugs Today (Barc) 2010; 46: 3-11.
123. Kushida CA, Becker PM, Ellenbogen AL, Canafax DM, Barrett RW; XP052 Study Group. Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS. Neurology 2009; 72: 439-446.
124. Walters AS, Ondo WG, Kushida CA, et al; XP045 Study Group. Gabapentin enacarbil in restless legs syndrome: a phase 2b, 2-week, randomized, double-blind, placebo-controlled trial. Clin Neuropharmacol 2009; 32: 311-320.
125. Kushida CA, Walters AS, Becker P, et al; XP021 Study Group. A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep 2009; 32: 159-168.
126. Bogan RK, Bornemann MA, Kushida CA, Trân PV, Barrett RW; XP060 Study Group. Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study. Mayo Clin Proc 2010; 85: 512-521. Erratum in: Mayo Clin Proc 2010; 85: 693-694.
127. Ellenbogen AL, Thein SG, Winslow DH, et al. A 52-week study of gabapentin enacarbil in restless legs syndrome. Clin Neuropharmacol 2011; 34: 8-16.
128. Lee DO, Ziman RB, Perkins AT, Poceta JS, Walters AS, Barrett RW; XP053 Study Group. A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. J Clin Sleep Med 2011; 7: 282-292.
129. Winkelman JW, Bogan RK, Schmidt MH, Hudson JD, DeRossett SE, Hill-Zabala CE. Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome. Mov Disord 2011; 26: 2065-2072.
130. Inoue Y, Uchimura N, Kuroda K, Hirata K, Hattori N. Long-term efficacy and safety of gabapentin enacarbil in Japanese restless legs syndrome patients. Prog Neuropsychopharmacol Biol Psychiatry 2012; 36: 251-257.
131. Sommer M, Bachmann CG, Liebetanz KM, Schindehütte J, Tings T, Paulus W. Pregabalin in restless legs syndrome with and without neuropathic pain. Acta Neurol Scand 2007; 115: 347-350.
132. Garcia-Borreguero D, Larrosa O, Williams AM, et al. Treatment of restless legs syndrome with pregabalin: a double-blind, placebo-controlled study. Neurology 2010; 74: 1897-1904.
133. Allen R, Chen C, Soaita A, et al. A randomized, double-blind, 6-week, dose-ranging study of pregabalin in patients with restless legs syndrome. Sleep Med 2010; 11: 512-519.
134. Youssef EA, Wagner ML, Martinez JO, Hening W. Pilot trial of lamotrigine in the restless legs syndrome. Sleep Med 2005; 6: 89.
135. Della Marca G, Vollono C, Mariotti P, et al. Levetiracetam can be effective in the treatment of restless legs syndrome with periodic limb movements in sleep: report of two cases. J Neurol Neurosurg Psychiatry 2006; 77: 566-567.
136. Gagliano A, Aricò I, Calarese T, et al. Restless leg syndrome in ADHD children: levetiracetam as a reasonable therapeutic option. Brain Dev 2010; xx: xx-xx.
137. Pérez Bravo A. Topiramate use as treatment in restless legs syndrome. Actas Esp Psiquiatr. 2004; 32(3): 132-7.
138. Lundvall O, Abom PE, Holm R. Carbamazepine in restless legs. A controlled pilot study. Eur J Clin Pharmacol 1983; 25: 323-324.
139. Telstad W, Sørensen O, Larsen S, Lillevold PE, Stensrud P, Nyberg-Hansen R. Treatment of the restless legs syndrome with carbamazepine: a double blind study. Br Med J (Clin Res Ed) 1984; 288: 444-446.
140. Jimenez-Trevino L. Oxcarbazepine treatment of restless legs syndrome: three case reports. Clin Neuropharmacol 2009; 32: 169-170.
141. Eisensehr I, Ehrenberg BL, Rogge Solti S, Noachtar S. Treatment of idiopathic restless legs syndrome (RLS) with slow-release valproic acid compared with slow-release levodopa/benserazid. J Neurol 2004; 251: 579-583.
142. Walters AS, Winkelmann J, Trenkwalder C. et al. Long-term follow-up on restless legs syndrome patients treated with opioids. Mov Disord. 2001; 16(6): 1105-9.
143. Ondo WG. Methadone for refractory restless legs syndrome. Mov Disord 2005; 20: 345-348.
144. Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC. QTc interval screening in methadone treatment. Ann Intern Med 2009; 150: 387-395.
145. Earley CJ, Heckler D, Allen RP. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med. 2004; 5(3): 231-5.
146. Ondo WG. Intravenous iron dextran for refractory restless legs syndrome. Sleep Med 2010; 11: 494-496.
147. Earley CJ, Heckler D, Allen RP. Repeated IV doses of iron provides effective supplemental treatment of restless legs syndrome. Sleep Med 2005; 6: 301-305.
148. Allen RP, Adler CH, Du W, Butcher A, Bregman DB, Earley CJ. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med 2011; 12: 906-913.
149. Auerbach M. Finding a safe and effective intravenous iron treatment for restless legs syndrome. Sleep Med 2010; 11: 429-430.
150. Aukerman MM, Aukerman D, Bayard M, Tudiver F, Thorp L, Bailey B. Exercise and restless legs syndrome: a randomized controlled trial. J Am Board Fam Med 2006; 19: 487-493.