Have a personal or library account? Click to login
A Narrative Review of the Lesser Known Medications for Treatment of Restless Legs Syndrome and Pathogenetic Implications for Their Use Cover

A Narrative Review of the Lesser Known Medications for Treatment of Restless Legs Syndrome and Pathogenetic Implications for Their Use

Open Access
|Mar 2023

References

  1. 1Yeh P, Walters AS, Tsuang JW. Restless Legs Syndrome: A Comprehensive Overview on Its Epidemiology, Risk Factors, and Treatment. Sleep Breath. 2012; 16(4): 9871007. DOI: 10.1007/s11325-011-0606-x
  2. 2Guay A, Houle M, O’Shaughnessy J, Descarreaux M. Current Evidence on Diagnostic Criteria, Relevant Outcome Measures, and Efficacy of Nonpharmacologic Therapy in the Management of Restless Legs Syndrome (Rls): A Scoping Review. J Manipulative Physiol Ther. 2020; 43(9): 93041. DOI: 10.1016/j.jmpt.2020.05.004
  3. 3Hening W. The Clinical Neurophysiology of the Restless Legs Syndrome and Periodic Limb Movements. Part I: Diagnosis, Assessment, and Characterization. Clin Neurophysiol. 2004; 115(9): 196574. DOI: 10.1016/j.clinph.2004.03.032
  4. 4Trenkwalder C, Hening WA, Montagna P, Oertel WH, Allen RP, Walters AS, Costa J, Stiasny-Kolster K, Sampaio C. Treatment of Restless Legs Syndrome: An Evidence-Based Review and Implications for Clinical Practice. Mov Disord. 2008; 23(16): 2267302. DOI: 10.1002/mds.22254
  5. 5de 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(10): 133542. DOI: 10.1002/mds.22955
  6. 6Aurora RN, Kristo DA, Bista SR, Rowley JA, Zak RS, Casey KR, Lamm CI, Tracy SL, Rosenberg RS, American Academy of Sleep M. 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(8): 103962. DOI: 10.5665/sleep.1988
  7. 7Silber MH, Buchfuhrer MJ, Earley CJ, Koo BB, Manconi M, Winkelman JW, Scientific, Medical Advisory Board of the Restless Legs Syndrome F. The Management of Restless Legs Syndrome: An Updated Algorithm. Mayo Clin Proc. 2021; 96(7): 192137. DOI: 10.1016/j.mayocp.2020.12.026
  8. 8Picchietti DL. “Restless Legs Syndrome and Periodic Limb Movement Disorder in Children.” Wolters Kluwer, https://www.uptodate.com/contents/restless-legs-syndrome-and-periodic-limb-movement-disorder-in-children/print?search=Restless%20Legs%20and%20Periodic%20Limb%20Movements%20in%20Children&source=search_result&selectedTitle=1~121&usage_type=default&display_rank=1 (accessed 2022.10.30).
  9. 9Harrison EG, Keating JL, Morgan PE. Non-Pharmacological Interventions for Restless Legs Syndrome: A Systematic Review of Randomised Controlled Trials. Disabil Rehabil. 2019; 41(17): 200614. DOI: 10.1080/09638288.2018.1453875
  10. 10Bega D, Malkani R. Alternative Treatment of Restless Legs Syndrome: An Overview of the Evidence for Mind-Body Interventions, Lifestyle Interventions, and Neutraceuticals. Sleep Medicine. 2016; 17: 99. DOI: 10.1016/j.sleep.2015.09.009
  11. 11Allen 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 Medicine. 2003; 4(2): 10119. DOI: 10.1016/S1389-9457(03)00010-8
  12. 12Xu X-M, Liu Y, Jia S-Y, Dong M-X, Cao D, Wei Y-D. Complementary and Alternative Therapies for Restless Legs Syndrome: An Evidence-Based Systematic Review. Sleep Medicine Reviews. 2018; 38: 15867. DOI: 10.1016/j.smrv.2017.06.003
  13. 13Mackie S, Winkelman JW. Long-Term Treatment of Restless Legs Syndrome (Rls): An Approach to Management of Worsening Symptoms, Loss of Efficacy, and Augmentation. CNS Drugs. 2015; 29(5): 351. DOI: 10.1007/s40263-015-0250-2
  14. 14Cuellar N, Galper DI, Taylor AG, D’Huyvetter K, Miederhoff P, Stubbs P. Restless Legs Syndrome. Journal of alternative and complementary medicine (New York, N.Y.). 2004; 10(3): 42223. DOI: 10.1089/1075553041323786
  15. 15Yan X, Wang W-D, Walters AS, Wang Q, Liu Y-J, Chu F-Y. Traditional Chinese Medicine Herbal Preparations in Restless Legs Syndrome (Rls) Treatment: A Review and Probable First Description of Rls in 1529. Sleep Medicine Reviews. 2012; 16(6): 50918. DOI: 10.1016/j.smrv.2012.01.003
  16. 16Mitchell UH. Medical Devices for Restless Legs Syndrome - Clinical Utility of the Relaxis Pad. Ther Clin Risk Manag. 2015; 11: 178994. DOI: 10.2147/TCRM.S87208
  17. 17Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C. Validation of the International Restless Legs Syndrome Study Group Rating Scale for Restless Legs Syndrome. Sleep Med. 2003; 4(2): 12132. DOI: 10.1016/S1389-9457(02)00258-7
  18. 18Popkin RJ. Orphenadrine Citrate (Norflex) for the Treatment of “Restless Legs” and Related Syndromes. J Am Geriatr Soc. 1971; 19(1): 769. DOI: 10.1111/j.1532-5415.1971.tb01557.x
  19. 19Ausserwinkler M, Schmidt P. Successful Clonidine Treatment of Restless Leg Syndrome in Chronic Kidney Insufficiency. Schweiz Med Wochenschr. 1989; 119(6): 1846.
  20. 20Pérez Bravo A. Topiramate Use as Treatment in Restless Legs Syndrome. Actas Esp Psiquiatr. 2004; 32(3): 1327
  21. 21Handwerker JV, Palmer RF JR.. Clonidine in the Treatment of “Restless Leg” Syndrome. N Engl J Med. 1985; 313(19): 12289. DOI: 10.1056/NEJM198511073131914
  22. 22Cavatorta F, Vagge R, Solari P, Queirolo C. Preliminary Results with Clonidine in the Restless Legs Syndrome in 2 Hemodialyzed Uremic Patients. Minerva urologica e nefrologica = The Italian journal of urology and nephrology. 1987; 39(1): 93.
  23. 23Bastani B, Westervelt FB. Effectiveness of Clonidine in Alleviating the Symptoms of “Restless Legs”. Am J Kidney Dis. 1987; 10(4): 326. DOI: 10.1016/S0272-6386(87)80034-3
  24. 24Bamford CR, Sandyk R. Failure of Clonidine to Ameliorate the Symptoms of Restless Legs Syndrome. Sleep. 1987; 10(4): 3989. DOI: 10.1093/sleep/10.4.398
  25. 25Wagner ML, Walters AS, Coleman RG, Hening WA, Grasing K, Chokroverty S. Randomized, Double-Blind, Placebo-Controlled Study of Clonidine in Restless Legs Syndrome. Sleep. 1996; 19(1): 528. DOI: 10.1093/sleep/19.1.52
  26. 26Zoe A, Wagner ML, Walters AS. High-Dose Clonidine in a Case of Restless Legs Syndrome. Ann Pharmacother. 1994; 28(7–8): 87881. DOI: 10.1177/106002809402800711
  27. 27Mechler K, Banaschewski T, Hohmann S, Häge A. Evidence-Based Pharmacological Treatment Options for Adhd in Children and Adolescents. Pharmacol Ther. 2022; 230: 107940. DOI: 10.1016/j.pharmthera.2021.107940
  28. 28Digne-Malcolm H, Frise MC, Dorrington KL. How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure. Front Physiol. 2016; 7: 320. DOI: 10.3389/fphys.2016.00320
  29. 29Garcia-Borreguero D, Silber MH, Winkelman JW, Högl B, Bainbridge J, Buchfuhrer M, Hadjigeorgiou G, Inoue Y, Manconi M, Oertel W, Ondo W, Winkelmann J, Allen RP. Guidelines for the First-Line Treatment of Restless Legs Syndrome/Willis-Ekbom Disease, Prevention and Treatment of Dopaminergic Augmentation: A Combined Task Force of the Irlssg, Eurlssg, and the Rls-Foundation. Sleep Med. 2016; 21: 111. DOI: 10.1016/j.sleep.2016.01.017
  30. 30Lexicomp. “Clonidine: Drug Information” https://www.uptodate.com/contents/clonidine-drug-information?search=clonidine%20drug%20information&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  31. 31Ferré S, Quiroz C, Guitart X, Rea W, Seyedian A, Moreno E, Casadó-Anguera V, Díaz-Ríos M, Casadó V, Clemens S, Allen RP, Earley CJ, García-Borreguero D. Pivotal Role of Adenosine Neurotransmission in Restless Legs Syndrome. Front Neurosci. 2017; 11: 722. DOI: 10.3389/fnins.2017.00722
  32. 32Ferré S, Quiroz C, Rea W, Guitart X, García-Borreguero D. Adenosine Mechanisms and Hypersensitive Corticostriatal Terminals in Restless Legs Syndrome. Rationale for the Use of Inhibitors of Adenosine Transport. Adv Pharmacol. 2019; 84: 319. DOI: 10.1016/bs.apha.2018.12.005
  33. 33Garcia-Borreguero D, Guitart X, Garcia Malo C, Cano-Pumarega I, Granizo JJ, Ferré S. Treatment of Restless Legs Syndrome/Willis-Ekbom Disease with the Non-Selective Ent1/Ent2 Inhibitor Dipyridamole: Testing the Adenosine Hypothesis. Sleep Med. 2018; 45: 9497. DOI: 10.1016/j.sleep.2018.02.002
  34. 34Garcia-Borreguero D, Garcia-Malo C, Granizo JJ, Ferré S. A Randomized, Placebo-Controlled Crossover Study with Dipyridamole for Restless Legs Syndrome. Mov Disord. 2021; 36(10): 238792. DOI: 10.1002/mds.28668
  35. 35Lexicomp. “Dipyridamole: Drug Information.” https://www.uptodate.com/contents/dipyridamole-drug-information?search=dipyridamole&source=panel_search_result&selectedTitle=1~104&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.11.02).
  36. 36Del Giovane C, Boncoraglio GB, Bertù L, Banzi R, Tramacere I. Antiplatelet Drugs for Secondary Prevention in Patients with Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Network Meta-Analysis. BMC Neurol. 2021; 21(1): 319. DOI: 10.1186/s12883-021-02341-2
  37. 37Allen RP, Barker PB, Horská A, Earley CJ. Thalamic Glutamate/Glutamine in Restless Legs Syndrome: Increased and Related to Disturbed Sleep. Neurology. 2013; 80(22): 202834. DOI: 10.1212/WNL.0b013e318294b3f6
  38. 38Garcia-Borreguero D, Cano I, Granizo JJ. Treatment of Restless Legs Syndrome with the Selective Ampa Receptor Antagonist Perampanel. Sleep Med. 2017; 34: 10508. DOI: 10.1016/j.sleep.2017.03.012
  39. 39Lexicomp. “Perampanel: Drug Information.” https://www.uptodate.com/contents/perampanel-drug-information?search=perampanel&source=panel_search_result&selectedTitle=1~15&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  40. 40Evidente VG, Adler CH, Caviness JN, Hentz JG, Gwinn-Hardy K. Amantadine Is Beneficial in Restless Legs Syndrome. Mov Disord. 2000; 15(2): 3247. DOI: 10.1002/1531-8257(200003)15:2<;324::AID-MDS1020>3.0.CO;2-4
  41. 41Lexicomp. “Amantadine: Drug Information.” https://www.uptodate.com/contents/amantadine-drug-information?search=amantadine&source=panel_search_result&selectedTitle=1~69&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  42. 42Kapur N, Friedman R. Oral Ketamine: A Promising Treatment for Restless Legs Syndrome. Anesth Analg. 2002; 94(6): 15589, table of contents. DOI: 10.1097/00000539-200206000-00034
  43. 43Lexicomp. “Ketamine: Drug Information.” https://www.uptodate.com/contents/ketamine-drug-information?search=ketamine&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2023.01.29).
  44. 44Lundvall O, Abom PE, Holm R. Carbamazepine in Restless Legs. A Controlled Pilot Study. Eur J Clin Pharmacol. 1983; 25(3): 3234. DOI: 10.1007/BF01037942
  45. 45Telstad 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(6415): 4446. DOI: 10.1136/bmj.288.6415.444
  46. 46Oztürk O, Eraslan D, Kumral E. Oxcarbazepine Treatment for Paroxetine-Induced Restless Leg Syndrome. Gen Hosp Psychiatry. 2006; 28(3): 2645. DOI: 10.1016/j.genhosppsych.2006.02.009
  47. 47Jimenez-Trevino L. Oxcarbazepine Treatment of Restless Legs Syndrome: Three Case Reports. Clin Neuropharmacol. 2009; 32(3): 16970. DOI: 10.1097/WNF.0b013e31818f1125
  48. 48Lexicomp. “Carbamazepine: Drug Information.” https://www.uptodate.com/contents/carbamazepine-drug-information?search=carbamazepine&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  49. 49Lexicomp. “Oxcarbazepine: Drug Information.” https://www.uptodate.com/contents/oxcarbazepine-drug-information?search=oxcarbazepine&source=panel_search_result&selectedTitle=1~121&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  50. 50Youssef EA, Wagner ML, Martinez JO, Hening W. Pilot Trial of Lamotrigine in the Restless Legs Syndrome. Sleep Med. 2005; 6(1): 89. DOI: 10.1016/j.sleep.2004.10.009
  51. 51McMeekin H. Treatment of Bipolar Disorder, Restless Legs Syndrome and Parkinsonian Symptoms Using Lamotrigine: A Report of Seven Patients. J S C Med Assoc. 2007; 103(3): 6973
  52. 52Lexicomp. “Lamotrigine: Drug Information.” https://www.uptodate.com/contents/lamotrigine-drug-information?search=lamotrigine&source=panel_search_result&selectedTitle=1~135&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.11.05).
  53. 53Romigi A, Izzi F, Placidi F, Sperli F, Cervellino A, Marciani MG. Topiramate-Induced Restless Legs Syndrome: A Report of Two Cases. J Neurol. 2007; 254(8): 11201. DOI: 10.1007/s00415-007-0243-z
  54. 54Bermejo PE. Restless Legs Syndrome Induced by Topiramate: Two More Cases. J Neurol. 2009; 256(4): 6623. DOI: 10.1007/s00415-009-0073-5
  55. 55Lexicomp. “Topiramate: Drug Information.” https://www.uptodate.com/contents/topiramate-drug-information?search=topiramate&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.11.01).
  56. 56Ehrenberg BL, Eisensehr I, Corbett KE, Crowley PF, Walters AS. Valproate for Sleep Consolidation in Periodic Limb Movement Disorder. J Clin Psychopharmacol. 2000; 20(5): 5748. DOI: 10.1097/00004714-200010000-00013
  57. 57Eisensehr 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(5): 57983. DOI: 10.1007/s00415-004-0367-6
  58. 58Lexicomp. “Valproate: Drug Information.” https://www.uptodate.com/contents/valproate-drug-information?search=valproic%20acid&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  59. 59Della Marca G, Vollono C, Mariotti P, Mazza M, Mennuni GF, Tonali P, Mazza S. 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(4): 5667. DOI: 10.1136/jnnp.2005.075671
  60. 60Gagliano A, Aricò I, Calarese T, Condurso R, Germanò E, Cedro C, Spina E, Silvestri R. Restless Leg Syndrome in Adhd Children: Levetiracetam as a Reasonable Therapeutic Option. Brain Dev. 2011; 33(6): 4806. DOI: 10.1016/j.braindev.2010.09.008
  61. 61Lexicomp. “Levetiracetam: Drug Information.” https://www.uptodate.com/contents/levetiracetam-drug-information?search=levetiracetam&source=panel_search_result&selectedTitle=1~108&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.11.03).
  62. 62Weinstock LB, Walters AS, Paueksakon P. Restless Legs Syndrome--Theoretical Roles of Inflammatory and Immune Mechanisms. Sleep Med Rev. 2012; 16(4): 34154. DOI: 10.1016/j.smrv.2011.09.003
  63. 63Hornyak M, Rupp A, Riemann D, Feige B, Berger M, Voderholzer U. Low-Dose Hydrocortisone in the Evening Modulates Symptom Severity in Restless Legs Syndrome. Neurology. 2008; 70(18): 16202. DOI: 10.1212/01.wnl.0000310984.45538.89
  64. 64Oscroft NS, Smith IE. Oral Glucocorticosteroids: Effective in a Case of Restless Legs Syndrome Resistant to Other Therapies. Sleep Med. 2010; 11(6): 596. DOI: 10.1016/j.sleep.2009.11.010
  65. 65Lexicomp. “Prednisolone (Systemic): Drug Information.” https://www.uptodate.com/contents/prednisolone-systemic-drug-information?search=glucocorticoids&selectedTitle=1~146&usage_type=panel&display_rank=1&kp_tab=drug_general&source=panel_search_result (accessed 2022.10.31).
  66. 66Lexicomp. “Hydrocortisone (Systemic): Drug Information.” https://www.uptodate.com/contents/hydrocortisone-systemic-drug-information?search=hydrocortisone&source=panel_search_result&selectedTitle=1~145&usage_type=panel&showDrugLabel=true&display_rank=1 (accessed 2022.11.07).
  67. 67Megelin T, Ghorayeb I. Cannabis for Restless Legs Syndrome: A Report of Six Patients. Sleep Med. 2017; 36: 18283. DOI: 10.1016/j.sleep.2017.04.019
  68. 68Samaha D, Kandiah T, Zimmerman D. Cannabis Use for Restless Legs Syndrome and Uremic Pruritus in in Patients Treated with Maintenance Dialysis: A Survey. Can J Kidney Health Dis. 2020; 7: 2054358120954944. DOI: 10.1177/2054358120954944
  69. 69Lexicomp. “Cannabidiol: Drug Information.” https://www.uptodate.com/contents/cannabidiol-drug-information?search=cannabidiol&source=panel_search_result&selectedTitle=1~53&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2023.01.28).
  70. 70Kolla BP, Mansukhani MP, Bostwick JM. The Influence of Antidepressants on Restless Legs Syndrome and Periodic Limb Movements: A Systematic Review. Sleep Med Rev. 2018; 38: 13140. DOI: 10.1016/j.smrv.2017.06.002
  71. 71Park YM, Lee HJ, Kang SG, Cho JH, Kim L. Resolution of Pregabalin and Mirtazapine Associated Restless Legs Syndrome by Bupropion in a Patient with Major Depressive Disorder. Psychiatry Investig. 2009; 6(4): 3135. DOI: 10.4306/pi.2009.6.4.313
  72. 72Lee JJ, Erdos J, Wilkosz MF, LaPlante R, Wagoner B. Bupropion as a Possible Treatment Option for Restless Legs Syndrome. Ann Pharmacother. 2009; 43(2): 3704. DOI: 10.1345/aph.1L035
  73. 73Kim 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(6): 298301. DOI: 10.1097/01.wnf.0000194706.61224.29
  74. 74Bayard M, Bailey B, Acharya D, Ambreen F, Duggal S, Kaur T, Rahman ZU, Roller K, Tudiver F. Bupropion and Restless Legs Syndrome: A Randomized Controlled Trial. J Am Board Fam Med. 2011; 24(4): 4228. DOI: 10.3122/jabfm.2011.04.100173
  75. 75Vishwakarma K, Kalra J, Gupta R, Sharma M, Sharma T. A Double-Blind, Randomized, Controlled Trial to Compare the Efficacy and Tolerability of Fixed Doses of Ropinirole, Bupropion, and Iron in Treatment of Restless Legs Syndrome (Willis-Ekbom Disease). Ann Indian Acad Neurol. 2016; 19(4): 47277. DOI: 10.4103/0972-2327.194424
  76. 76Lexicomp. “Bupropion: Drug Information.” https://www.uptodate.com/contents/bupropion-drug-information?search=bupropion&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  77. 77Guilleminault C, Flagg W. Effect of Baclofen on Sleep-Related Periodic Leg Movements. Ann Neurol. 1984; 15(3): 2349. DOI: 10.1002/ana.410150304
  78. 78Sandyk R, Kwo-on-Yuen PF, Bamford CR. The Effects of Baclofen in the Restless Legs Syndrome: Evidence for Endogenous Opioid Involvement. J Clin Psychopharmacol. 1988; 8(6): 4401. DOI: 10.1097/00004714-198812000-00017
  79. 79Brown 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(5): 5914. DOI: 10.1093/sleep/23.5.1a
  80. 80Lexicomp. “Baclofen: Drug Information.” https://www.uptodate.com/contents/baclofen-drug-information?search=baclofen&source=panel_search_result&selectedTitle=1~96&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  81. 81Alpert CC, Tobin DP, Dierdorf SF. Physostigmine for the Acute Treatment of Restless Legs Syndrome. Anesth Analg. 2005; 101(3): 72627. DOI: 10.1213/01.ANE.0000159376.47974.71
  82. 82Peacock J, Mishra G, Roy RC. Physostigmine and Restless Legs Syndrome. Anesthesiology. 2012; 117(5): 11445. DOI: 10.1097/ALN.0b013e31826e7038
  83. 83Lexicomp. “Physostigmine: Drug Information.” https://www.uptodate.com/contents/physostigmine-drug-information?search=physostigmine&source=panel_search_result&selectedTitle=1~25&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2023.01.29).
  84. 84Lexicomp. “Orphenadrine: Drug Information.” https://www.uptodate.com/contents/orphenadrine-drug-information?search=orphenadrine&source=panel_search_result&selectedTitle=1~9&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.11.01).
  85. 85Weinstock LB, Walters AS. Restless Legs Syndrome Is Associated with Irritable Bowel Syndrome and Small Intestinal Bacterial Overgrowth. Sleep Med. 2011; 12(6): 6103. DOI: 10.1016/j.sleep.2011.03.007
  86. 86Weinstock LB, Fern SE, Duntley SP. Restless Legs Syndrome in Patients with Irritable Bowel Syndrome: Response to Small Intestinal Bacterial Overgrowth Therapy. Dig Dis Sci. 2008; 53(5): 12526. DOI: 10.1007/s10620-007-0021-0
  87. 87Weinstock LB. Antibiotic Therapy May Improve Idiopathic Restless Legs Syndrome: Prospective, Open-Label Pilot Study of Rifaximin, a Nonsystemic Antibiotic. Sleep Med. 2010; 11(4): 427. DOI: 10.1016/j.sleep.2009.06.005
  88. 88Lexicomp. “Rifaximin: Drug Information.” https://www.uptodate.com/contents/rifaximin-drug-information?search=rifaximin&source=panel_search_result&selectedTitle=1~45&usage_type=panel&kp_tab=drug_general&display_rank=1 (accessed 2022.10.31).
  89. 89Rotenberg JS, Canard K, Difazio M. Successful Treatment of Recalcitrant Restless Legs Syndrome with Botulinum Toxin Type-A. J Clin Sleep Med. 2006; 2(3): 2758. DOI: 10.5664/jcsm.26585
  90. 90Mittal SO, Machado D, Richardson D, Dubey D, Jabbari B. Botulinum Toxin in Restless Legs Syndrome-a Randomized Double-Blind Placebo-Controlled Crossover Study. Toxins (Basel). 2018; 10(10). DOI: 10.3390/toxins10100401
  91. 91Agarwal P, Sia C, Vaish N, Roy-Faderman I. Pilot Trial of Onabotulinumtoxina (Botox) in Moderate to Severe Restless Legs Syndrome. Int J Neurosci. 2011; 121(11): 6225. DOI: 10.3109/00207454.2011.602774
  92. 92Ghorayeb I, Bénard A, Vivot A, Tison F, Burbaud P. A Phase Ii, Open-Label, Non-Comparative Study of Botulinum Toxin in Restless Legs Syndrome. Sleep Med. 2012; 13(10): 13136. DOI: 10.1016/j.sleep.2012.08.019
  93. 93Nahab FB, Peckham EL, Hallett M. Double-Blind, Placebo-Controlled, Pilot Trial of Botulinum Toxin a in Restless Legs Syndrome. Neurology. 2008; 71(12): 9501. DOI: 10.1212/01.wnl.0000325994.93782.a1
  94. 94Lexicomp. “Onabotulinumtoxina (Botox): Drug Information “Onabotulinumtoxina (Botox): Drug Information - Uptodate”.” https://www.uptodate.com/contents/onabotulinumtoxina-botox-drug-information?source=auto_suggest&selectedTitle=1~1---1~4---botox&search=botox
  95. 95Lexicomp. “Rimabotulinumtoxinb (Myobloc): Drug Information.” https://www.uptodate.com/contents/rimabotulinumtoxinb-myobloc-drug-information?source=auto_suggest&selectedTitle=1~1---1~4---rimabotulinum&search=rimabotulinumtoxinb (accessed 2023.01.23).
  96. 96Grewal M, Hawa R, Shapiro C. Treatment of Periodic Limb Movements in Sleep with Selegiline Hcl. Mov Disord. 2002; 17(2): 398401. DOI: 10.1002/mds.10082
  97. 97Lexicomp. “Selegiline: Drug Information.” https://www.uptodate.com/contents/selegiline-drug-information?source=auto_suggest&selectedTitle=1~1---1~4---selegiline&search=selegiline (accessed 2023.01.29).
  98. 98Jhoo JH, Yoon IY, Kim YK, Chung S, Kim JM, Lee SB, Kim TH, Moon SH, Kim SE, Kim KW. Availability of Brain Serotonin Transporters in Patients with Restless Legs Syndrome. Neurology. 2010; 74(6): 5138. DOI: 10.1212/WNL.0b013e3181cef824
  99. 99Lexicomp. “Cyproheptadine: Drug Information.” https://www.uptodate.com/contents/cyproheptadine-drug-information?source=auto_suggest&selectedTitle=1~1---1~4---cyproheptadine&search=cyproheptadine (accessed 2023.01.29). DOI: 10.1093/sleep/zsz223
  100. 100Lai YY, Hsieh KC, Cheng YH, Chew KT, Nguyen D, Ramanathan L, Siegel JM. Striatal Histamine Mechanism in the Pathogenesis of Restless Legs Syndrome. Sleep. 2020; 43(2). DOI: 10.1093/sleep/zsz223
  101. 101Meskill GJ, Davis CW, Zarycranski D, Doliba M, Schwartz JC, Dayno JM. Clinical Impact of Pitolisant on Excessive Daytime Sleepiness and Cataplexy in Adults with Narcolepsy: An Analysis of Randomized Placebo-Controlled Trials. CNS Drugs. 2022; 36(1): 6169. DOI: 10.1007/s40263-021-00886-x
  102. 102Poceta JS, Parsons L, Engelland S, Kripke DF. Circadian Rhythm of Csf Monoamines and Hypocretin-1 in Restless Legs Syndrome and Parkinson’s Disease. Sleep Med. 2009; 10(1): 12933. DOI: 10.1016/j.sleep.2007.11.002
  103. 103Allen RP, Mignot E, Ripley B, Nishino S, Earley CJ. Increased Csf Hypocretin-1 (Orexin-a) in Restless Legs Syndrome. Neurology. 2002; 59(4): 63941. DOI: 10.1212/WNL.59.4.639
  104. 104Stiasny-Kolster K, Mignot E, Ling L, Möller JC, Cassel W, Oertel WH. Csf Hypocretin-1 Levels in Restless Legs Syndrome. Neurology. 2003; 61(10): 14269. DOI: 10.1212/01.WNL.0000094196.50155.38
  105. 105Lexicomp. “Pitolisant: Drug Information.” https://www.uptodate.com/contents/pitolisant-drug-information?source=auto_suggest&selectedTitle=1~1---1~4---pitol&search=pitolisant (accessed 2023.01.29).
  106. 106Winkelman JW, Schoerning L, Platt S, Jensen JE. Restless Legs Syndrome and Central Nervous System Gamma-Aminobutyric Acid: Preliminary Associations with Periodic Limb Movements in Sleep and Restless Leg Syndrome Symptom Severity. Sleep Med. 2014; 15(10): 122530. DOI: 10.1016/j.sleep.2014.05.019
  107. 107Jiménez-Jiménez FJ, Esguevillas G, Alonso-Navarro H, Zurdo M, Turpín-Fenoll L, Millán-Pascual J, Adeva-Bartolomé T, Cubo E, Navacerrada F, Amo G, Rojo-Sebastián A, Rubio L, Díez-Fairén M, Pastor P, Calleja M, Plaza-Nieto JF, Pilo-de-la-Fuente B, Arroyo-Solera M, García-Albea E, Agúndez JAG, García-Martín E. Gamma-Aminobutyric Acid (Gaba) Receptors Genes Polymorphisms and Risk for Restless Legs Syndrome. Pharmacogenomics J. 2018; 18(4): 56577. DOI: 10.1038/s41397-018-0023-7
  108. 108Sills GJ, Rogawski MA. Mechanisms of Action of Currently Used Antiseizure Drugs. Neuropharmacology. 2020; 168: 107966. DOI: 10.1016/j.neuropharm.2020.107966
DOI: https://doi.org/10.5334/tohm.739 | Journal eISSN: 2160-8288
Language: English
Submitted on: Nov 20, 2022
Accepted on: Feb 11, 2023
Published on: Mar 2, 2023
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2023 Paul G. Yeh, Karen Spruyt, Lourdes M. DelRosso, Arthur S. Walters, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.