Gabapentin enacarbil for the treatment of restless legs syndrome (RLS)

Expert Opinion on Pharmacotherapy

Volumn 12, Issue 18, 2011, Pages 2905-2914

  Burke, Rachel A ^a   Faulkner, Michele A ^a  

^a CREIGHTON UNIVERSITY   (United States)

Author keywords

Gabapentin enacarbil; Horizant; Restless legs syndrome; RLS; Solzira

Indexed keywords

BENZODIAZEPINE; DOPAMINE RECEPTOR STIMULATING AGENT; GABAPENTIN; GABAPENTIN ENACARBIL; OPIATE DERIVATIVE; PLACEBO;

CONTROLLED CLINICAL TRIAL (TOPIC); DAYTIME SOMNOLENCE; DIARRHEA; DIZZINESS; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG INFORMATION; DRUG RESEARCH; DRUG SAFETY; FATIGUE; HEADACHE; HUMAN; INSOMNIA; NAUSEA; RESTLESS LEGS SYNDROME; REVIEW; SOMNOLENCE;

ADMINISTRATION, ORAL; CALCIUM CHANNELS; CARBAMATES; CLINICAL TRIALS AS TOPIC; GAMMA-AMINOBUTYRIC ACID; HUMANS; MOLECULAR STRUCTURE; PROTEIN BINDING; RESTLESS LEGS SYNDROME; TREATMENT OUTCOME;

EID: 81855183745     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2011.635645     Document Type: Review

References (76)

1. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005;12(11):1286-92
2. Hening W, Walters AS, Allen RP, et al. 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(3):237-46
3. Allen RP, Earley CJ. Restless legs syndrome: a review of clinical and pathophysiologic features. J Clin Neurophysiol 2011;18(2):128-47
4. Manconi M, Govoni V, De Vito A, et al. Pregnancy as a risk factor for restless legs syndrome. Sleep Med 2004;5:305-8
5. Goodman JD, Brodie C, Ayida GA. Restless leg syndrome in pregnancy. Br Med J 1988;297:1101-2
6. Allen R, Picchietti D, Hening W, et al. 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
7. Hening W, Allen R, Earley C, et al. The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review. Sleep 1999;22(7):970-99
8. Natarajan R. Review of periodic limb movement and restless leg syndrome. J Postgrad Med 2010;56:157-62
9. Ondo WG, Vuong KD, Wang Q. Restless legs syndrome in monozygotic twins: clinical correlates. Neurology 2000;55:1404-6
10. Winkelmann J, Schadrack J, Wetter TC, et al. Opioid and dopamine antagonist drug challenges in untreated restless legs syndrome patients. Sleep Med 2001;2:57-61
11. Neafsey PJ. Role of medications in the etiology and treatment of restless leg syndrome. Home Healthc Nurse 2005;23:207-9
12. Tunc T, Karadag YS, Dogulu F, Inan LE. Predisposing factors of restless legs syndrome in pregnancy. Mov Disord 2007;22:627-31
13. Sun ER, Chen CA, Ho G, et al. Iron and the restless legs syndrome. Sleep 1998;21(4):371-7
14. Allen RP, Barker PB, Wehrl F, et al. MRI measurement of brain iron in patients with restless legs syndrome. Neurology 2001;56:263-5
15. Beard JL, Connor JR. Iron status and neural functioning. Annu Rev Nutr 2003;23:41-58
16. Walters AS. Review of receptor agonist and antagonist studies relevant to the opiate system in restless legs syndrome. Sleep Med 2002;3:301-4
17. Walter AS, Ondo WG, Zhu W, Le W. Does the endogenous opiate system play a role in the restless legs syndrome?: a pilot post-mortem study. J Neurol Sci 2009;15:62-5
18. Allen R. Dopamine and iron in the pathophysiology of restless legs syndrome (RLS).Sleep Med 2004;5:385-91
19. Allen RP, Earley CJ. The role of iron in restless legs syndrome. Mov Disord 2007;22(Suppl 18):440-8
20. Quinn C, Uzbeck M, Saleem I, et al. Iron status and chronic kidney disease predict restless legs syndrome in an older hospital population. Sleep Med 2011;12(3):295-301
21. Silber MH, Ehrenberg BL, Allen RP, et al. An algorithm for the management of restless legs syndrome. Mayo Clin Proc 2004;79(7):916-22
22. O'Keefe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing 1994;23(3):200-3
23. Davis BJ, Rajput A, Rajput ML, et al. A randomized, double-blind placebocontrolled trial of iron in restless legs syndrome. Eur Neurol 2000;43:70-5
24. Wang J, O'Reilly B, Venkataraman R, et al. Efficacy of oral iron in patients with restless legs syndrome and low-normal ferritin: a randomized, double-blind, placebo-controlled study. Sleep Med 2009;10:973-5
25. Walters AS, Elin RJ, Cohen B, et al. Magnesium not likely to play a major role in the pathogenesis of Restless Legs Syndrome: serum and cerebrospinal fluidstudies [Letter to the editor]. Sleep Med 2007;8:186-7
26. Hornyak M, Voderholzer U, Hohagen F, et al. Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Sleep 1998;21(5):501-5
27. Trenkwalder C, Hening WA, Montagna P, et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinic practice. Mov Disord 2008;23:2267-302
28. 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(4):335-41
29. Botez MI, Lambert B. Folate deficiency and restless-legs syndrome in pregnancy. N Engl J Med 1977;297(12):670
30. Allen RP, Earley C. Augmentation of the restless legs syndrome with carbidopa/ levodopa. Sleep 1996;19(3):205-13
31. Guilleminault C, Cetel M, Philip P. Dopaminergic treatment of restless legs and rebound phenomenon. Neurology 1993;43(2):445
32. Earley CJ, Allen RP. Pergolide and carbidopa/levodopa treatment of the restless legs syndrome and periodic leg movements in sleep in a consecutive series of patients. Sleep 1996;19(10):801-10
33. Benes H, Kurella B, Kummer J, et al. Rapid onset of action of levodopa in restless legs syndrome: a double-blind, randomized, multicenter, crossover trial. Sleep 1999;22(8):1073-81
34. Trenkwalder C, Stiasny K, Pollmacher T, et al. L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial. Sleep 1995;18(8):681-8
35. Scholz H, Trenkwalder C, Kohnen R, et al. Levodopa for restless legs syndrome. Cochrane Database Syst Rev 2011;16(2):CD005504
36. Trenkwalder C, Garcia-Borreguero D, Montagna P, et al. Ropinirole in the treatment of restless legs syndrome: results from the TREAT RLS 1 study, a 12 week, randomized, placebo controlled study in 10 European countries. J Neurol Neurosurg Psychiatry 2004;75(1):92-7
37. 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(2):213-19
38. Trenkwalder C, Hundemer HP, Lledo A, et al. Efficacy of pergolide in treatment of restless legs syndrome: the PEARLS study. Neurology 2004;62(8):1391-7
39. Stiasny-Kolster K, Benes H, Peglau I, et al. Effective cabergoline treatment in idiopathic restless legs syndrome. Neurology 2004;63(12):2272-9
40. Partinen M, Hirvonen K, Jama L, et al. Open-label study of the long-term efficacy and safety of pramipexole in patients with restless legs syndrome (extension of the PRELUDE study).Sleep Med 2008;9:537-41
41. Kushida CA, Geyer J, Tolson JM, Asgharian A. Patient- and physician-rated measures demonstrate the effectiveness of ropinirole in the treatment of restless legs syndrome. Clin Neuropharmacol 2008;31(5):281-6
42. Staedt J, Wassmuth F, Ziemann U, et al. Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS).A doubleblind randomized crossover trial of pergolide versus L-Dopa. J Neural Transm 1997;104(4-5):461-8
43. Trenkwalder C, Benes H, Grote L, et al. Cabergoline compared to levodopa in the treatment of patients with severe restless legs syndrome: results from a multi-center, randomized, active controlled trial. Mov Disord 2007;22(5):696-703
44. Scholz H, Trenkwalder C, Kohnen R, et al. Dopamine agonists for restless legs syndrome. Cochrane Database Syst Rev 2011;16(3):CD006009
45. Trenkwalder C, Benes H, Poewe W, et al. Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomizes, double-blind, placebo-controlled trial. Lancet Neurol 2008;7:595-604
46. Oertel WH, Benes H, Garcia-Borreguero D, et al. 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;9:228-39
47. Oertel W, Trenkwalder C, Benes H, et al. 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;10:710-20
48. Winkelman JW, Sethi KD, Kushida CA, et al. Efficacy and safety of pramipexole in restless legs syndrome. Neurology 2006;67:1034-9
49. Walters AS, Ondo WG, Dreykluft T, et al. 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(12):1414-23
50. Tippmann-Piekert M, Park JG, Boeve BF, et al. Pathologic gambling in patients with restless legs syndrome treated with dopaminergic agonists. Neurology 2007;68:301-3
51. Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest 2006;130(5):1596-604
52. Lauerma H, Markkula J. Treatment of restless legs syndrome with tramadol: an open study. J Clin Psychiatry 1999;60:241-4
53. Earley CJ. Restless legs syndrome. N Engl J Med 2003;348:2103-9
54. Ondo WG. Methadone for refractory restless legs syndrome. Mov Disord 2005;20(3):345-8
55. Walters AS, Wagner ML, Hening WA, et al. Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep 1993;16(4):327-32
56. Montagna P, Sassoli de Bianchi L, Zucconi M, et al. Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand 1984;69(6):428-30
57. Boghen D, Lamonthe L, Elie R, et al. The treatment of the restless legs syndrome with clonazepam: a prospective controlled study. Can J Neurol Sci 1986;13(3):245-7
58. Stewart BH, Kugler AR, Thompson PR, Bockbrader HN. A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma. Pharm Res 1993;10(2):276-81
59. Lal R, Sukbuntherng J, Luo W, et al. Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers. Clin Ther 2009;31:1776-86
60. Neurontin (gabapentin) [package insert]. July 2010
61. Gidal BE, Radulovic LL, Kruger S, et al. Inter- and intra-subject variability in gabapentin absorption and absolute bioavailability. Epilepsy Res 2000;40(2-3):123-7
62. Garcia-Borreguero D, Larrosa O, de la Llave Y, et al. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology 2002;59:1573-9
63. Happe S, Sauter C, Klosch G, et al. Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 2003;48(2):82-6
64. 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(1):104-8
65. Micozkadioglu H, Ozdemir FN, Kut A, et al. Gabapentin versus levodopa for the treatment of restless legs syndrome in hemodialysis patients: an open-label study. Ren Fail 2004;26(4):393-7
66. Mellick GA, Mellick LB. Management of restless legs syndrome with gabapentin (Neurontin).Sleep 1996;19(3):224-6
67. Adler CH. Treatment of restless legs syndrome with gabapentin. Clin Neuropharmacol 1997;20(2):148-51
68. Cundy KC, Sastry S, Luo W, et al. Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J Clin Pharmacol 2008;48:1378-88
69. Lal R, Sukbuntherng J, Luo W, et al. The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral dministration of gabapentin enacarbil. Int J Clin Pharmacol Ther 2010;48(2):120-8
70. 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
71. Kushida CA, Walters AS, Becker P, et al. A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep 2009;32(2):159-68
72. Kushida CA, Becker PM, Ellenbogen AL, et al. Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS. Neurology 2009;72:439-46
73. Bogan RK, Cramer Bornemann MA, Kushida CA, et al. Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study. Mayo Clin Proc 2010;85(6):512-21
74. Lee DO, Ziman RB, Perkins AT, et al. 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(3):282-92
75. Zomorodi K, Lal R, Atluri H, et al. A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics and tolerability of gabapentin enacarbil in subjects with restless legs syndrome. J Clin Pharmacol 2009;49(9):1122
76. 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