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Restless-legs-Syndrom, periodische Gliedmaßenbewegungen im Schlaf und Psychopharmakologie

Restless legs syndrome, periodic limb movements, and psychopharmacology

Zusammenfassung

Das Restless-legs-Syndrom (RLS) und das Syndrom der periodischen Gliedmaßenbewegungen (PLMS) finden sich in der Allgemeinbevölkerung mit einer hohen Prävalenz als primäre Form. Neben organischen Faktoren kann ein sekundäres RLS/PLMS durch verschiedene Medikamente, vor allem durch Psychopharmaka, ausgelöst werden. In Fallberichten und kleinen Fallserien wurden bei einigen Antidepressiva, Antipsychotika, Lithium und einem Entzug von Opioiden eine Auslösung oder Verstärkung eines RLS und PLMS beschrieben, während verschiedene als Phasenprophylaktika eingesetzte Antiepileptika sowie einige Benzodiazepine von therapeutischem Nutzen sein können. Systematische Untersuchungen oder kontrollierte Studien zu diesen unerwünschten Effekten von Psychopharmaka sind bislang nicht durchgeführt worden. Zu den Antidepressiva mit einer erhöhten Auftretenswahrscheinlichkeit von RLS/PLMS zählen die selektiven Serotoninwiederaufnahmehemmer, Venlafaxin sowie einige tetrazyklische Antidepressiva; für verschiedene trizyklische Substanzen wurden vermehrt PLMS beobachtet. Für einige Antidepressiva mit anderem Transmitterprofil wie etwa Bupropion wurden in meist kleineren Studien RLS-/PLMS-lindernde oder zumindest diesbezüglich neutrale Effekte (Trazodon, Nortriptylin) beschrieben.

Im Falle eines Fortbestehens oder eines Neuauftretens einer Insomnie unter Psychopharmakotherapie sollte eine genaue Anamnese erhoben werden, um das Vorliegen eines RLS/PLMS als mögliche unerwünschte Arzneimittelwirkung zu identifizieren. Falls klinisch möglich, sollte ein Umsetzversuch auf eine andere Substanz vorgenommen werden. Zur Behandlung eines RLS/PLMS bei psychotischen Patienten kann zusätzlich zum Umsetzen des Antipsychotikums eine Behandlung mit einem Antiepileptikum oder einem Benzodiazepin in Erwägung gezogen werden.

Summary

Restless legs syndrome (RLS) and the often associated periodic limb movement disorder in sleep (PLMD) frequently occur in the general population as a primary disorder. In addition to organic disease, secondary forms are caused by psychotropic medication. Several antidepressants, antipsychotics, lithium, and opioid withdrawal have been shown to induce or exacerbate RLS and PLMD, while several antiepileptics used as mood stabilizers and some benzodiazepines demonstrate therapeutic potential for treating RLS/PLMD. Systematic or controlled studies for evaluating these side effects still do not exist. Among the antidepressants at higher risk of inducing this disorder are selective serotonin reuptake inhibitors, venlafaxine, and some tetracyclic antidepressants. Under medication with some tricyclic substances, periodic limb movements were observed more often. For some antidepressants with differing transmitter profiles such as bupropion RLS/PLMD ameliorating effects or at least neutral effects (Trazodon, Nortriptylin) have been described in small studies. In case of continued of or newly occurring insomnia a thorough history should be taken to identify a possible RLS/PLMD as an intolerable side effect of treatment. A change in medications should be considered if clinically feasible. In case of RLS/PLMD occurring in psychotic patients switching the antipsychotic and additionally using a second line medication such as antiepileptics or a benzodiazepine should be considered.

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Literatur

  1. Abetz L, Allen R, Follet A et al. (2004) Evaluating the quality of life of patients with restless legs syndrome. Clin Ther 26: 925–935

    PubMed  Article  Google Scholar 

  2. Adler CH (1997) Treatment of restless legs syndrome with gabapentin. Clin Neuropharmacol 20: 148–151

    PubMed  Article  CAS  Google Scholar 

  3. Agargun MY, Kara H, Ozbek H (2002) Restless legs syndrome induced by mirtazapine. J Clin Psychiatry 63: 1179

    PubMed  Google Scholar 

  4. Aiken CB (2007) Pramipexole in psychiatry: a systematic review of the literature. J Clin Psychiatry 68: 1230–1236

    PubMed  CAS  Google Scholar 

  5. Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113: 296–320

    PubMed  Article  CAS  Google Scholar 

  6. Allen RP, Picchietti D, Hening WA (2003) 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 4: 101–119

    PubMed  Article  Google Scholar 

  7. Bahk WM, Pae CU, Chae JH (2002) Mirtazapine may have the propensity for developing a restless legs syndrome? A case report. Psychiatry Clin Neurosci 56: 209–210

    PubMed  Article  Google Scholar 

  8. Bakshi R (1996) Fluoxetine and restless legs syndrome. J Neurol Sci 142: 151–152

    PubMed  Article  CAS  Google Scholar 

  9. Barnes TR, Braude WM (1985) Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry 42: 874–878

    PubMed  CAS  Google Scholar 

  10. Berger K, Kurth T (2007) RLS epidemiology-Frequencies, risk factors and methods in population studies. Mov Disord 23: 1200–1202

    Google Scholar 

  11. Bezerra ML, Martinez JV (2002) Zolpidem in restless legs syndrome. Eur Neurol 48: 180–181

    PubMed  Article  CAS  Google Scholar 

  12. Bonin B, Vandel P, Kantelip JP (2000) Mirtazapine and restless leg syndrome: a case report. Therapie 55: 655–656

    PubMed  CAS  Google Scholar 

  13. Bonnet MH, Arand DL (1990) The use of triazolam in older patients with periodic leg movements, fragmented sleep, and daytime sleepiness. J Gerontol 45: M139–144

    PubMed  CAS  Google Scholar 

  14. Brandt-Christensen M, Kvist K, Nilsson FM et al. (2006) Treatment with antidepressants and lithium is associated with increased risk of treatment with antiparkinson drugs: a pharmacoepidemiological study. J Neurol Neurosurg Psychiatry 77: 781–783

    PubMed  Article  CAS  Google Scholar 

  15. Buysse DJ, Reynolds CF 3rd, Hoch CC et al. (1996) Longitudinal effects of nortriptyline on EEG sleep and the likelihood of recurrence in elderly depressed patients. Neuropsychopharmacology 14: 243–252

    PubMed  Article  CAS  Google Scholar 

  16. Casas M, Garcia-Ribera C, Alvarez E et al. (1987) Myoclonic movements as a side-effect of treatment with therapeutic doses of clomipramine. Int Clin Psychopharmacol 2: 333–336

    PubMed  Article  CAS  Google Scholar 

  17. Chang CC, Shiah IS, Chang HA, Mao WC (2006) Does domperidone potentiate mirtazapine-associated restless legs syndrome? Prog Neuropsychopharmacol Biol Psychiatry 30: 316–318

    PubMed  Article  CAS  Google Scholar 

  18. Cohrs S (2008) Sleep Disturbances in Patients with Schizophrenia: Impact and Effect of Antipsychotics. CNS Drugs 22(11): 939–962

    PubMed  Article  CAS  Google Scholar 

  19. Cohrs S, Rodenbeck A, Guan Z et al. (2004) Sleep-promoting properties of quetiapine in healthy subjects. Psychopharmacology (Berl) 174: 421–429

    Google Scholar 

  20. Doghramji K, Browman CP, Gaddy JR, Walsh JK (1991) Triazolam diminishes daytime sleepiness and sleep fragmentation in patients with periodic leg movements in sleep. J Clin Psychopharmacol 11: 284–290

    PubMed  Article  CAS  Google Scholar 

  21. Dorsey CM, Lukas SE, Cunningham SL (1996) Fluoxetine-induced sleep disturbance in depressed patients. Neuropsychopharmacology 14: 437–442

    PubMed  Article  CAS  Google Scholar 

  22. Duggal HS, Mendhekar DN (2007) Clozapine-associated restless legs syndrome. J Clin Psychopharmacol. 27: 89–90

    Google Scholar 

  23. Ehrenberg BL, Eisensehr I, Corbett KE et al. (2000) Valproate for sleep consolidation in periodic limb movement disorder. J Clin Psychopharmacol 20: 574–578

    PubMed  Article  CAS  Google Scholar 

  24. Eisensehr I, Ehrenberg BL, Rogge Solti S, Noachtar S (2004) Treatment of idiopathic restless legs syndrome (RLS) with slow-release valproic acid compared with slow-release levodopa/benserazid. J Neurol 251: 579–583

    PubMed  Article  CAS  Google Scholar 

  25. Freye E, Levy J (2000) Acute abstinence syndrome following abrupt cessation of long-term use of tramadol (Ultram): a case study. Eur J Pain 4: 307–311

    PubMed  Article  CAS  Google Scholar 

  26. Freye E, Levy JV, Partecke L (2004) Use of gabapentin for attenuation of symptoms following rapid opiate detoxification (ROD) – correlation with neurophysiological parameters. Neurophysiol Clin 34: 81–89

    PubMed  Article  CAS  Google Scholar 

  27. Garcia-Borreguero D, Larrosa O, de la Llave Y et al. (2002) Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology 59: 1573–1579

    PubMed  CAS  Google Scholar 

  28. Guilleminault C, Crowe C, Quera-Salva MA et al. (1988) Periodic leg movement, sleep fragmentation and central sleep apnoea in two cases: reduction with Clonazepam. Eur Respir J 1: 762–765

    PubMed  CAS  Google Scholar 

  29. Guilleminault C, Raynal D, Takahashi S et al. (1976) Evaluation of short-term and long-term treatment of the narcolepsy syndrome with clomipramine hydrochloride. Acta Neurol Scand 54: 71–87

    PubMed  CAS  Article  Google Scholar 

  30. Happe S, Klosch G, Saletu B, Zeitlhofer J (2001) Treatment of idiopathic restless legs syndrome (RLS) with gabapentin. Neurology 57: 1717–1719

    PubMed  CAS  Google Scholar 

  31. Happe S, Sauter C, Klosch G et al. (2003) Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome. Neuropsychobiology 48: 82–86

    PubMed  Article  CAS  Google Scholar 

  32. Hargrave R, Beckley DJ (1998) Restless leg syndrome exacerbated by sertraline. Psychosomatics 39: 177–178

    PubMed  CAS  Google Scholar 

  33. Heiman EM, Christie M (1986) Lithium-aggravated nocturnal myoclonus and restless legs syndrome. Am J Psychiatry 143: 1191–1192

    PubMed  CAS  Google Scholar 

  34. Horiguchi J, Inami Y, Sasaki A et al. (1992) Periodic leg movements in sleep with restless legs syndrome: effect of clonazepam treatment, Jpn J Psychiatry Neurol 46: 727–732

    Google Scholar 

  35. Hornyak M, Kopasz M, Rodenbeck A et al. (2006) Influence of low-dose doxepin on periodic leg movements in primary insomnia patients. Somnologie 9: 111–115

    Article  Google Scholar 

  36. Jaskiw GE, Popli AP (2004) A meta-analysis of the response to chronic L-dopa in patients with schizophrenia: therapeutic and heuristic implications. Psychopharmacology (Berl) 171: 365–374

    Google Scholar 

  37. Kang SG, Lee HJ, Jung SW et al. (2007) Characteristics and clinical correlates of restless legs syndrome in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 31: 1078–1083

    PubMed  Article  Google Scholar 

  38. Kim SW, Shin IS, Kim JM et al. (2005) Bupropion may improve restless legs syndrome: a report of three cases. Clin Neuropharmacol 28: 298–301

    PubMed  Article  Google Scholar 

  39. Kraus T, Schuld A, Pollmacher T (1999) Periodic leg movements in sleep and restless legs syndrome probably caused by olanzapine. J Clin Psychopharmacol 19: 478–479

    PubMed  Article  CAS  Google Scholar 

  40. Larsen S, Telstad W, Sorensen O (1985) Carbamazepine therapy in restless legs. Discrimination between responders and non-responders. Acta Med Scand 218: 223–227

    PubMed  CAS  Google Scholar 

  41. Lauerma H, Markkula J(1999) Treatment of restless legs syndrome with tramadol: an open study. J Clin Psychiatry 60: 241–244

    PubMed  CAS  Google Scholar 

  42. Lundvall O, Abom PE, Holm R (1983) Carbamazepine in restless legs. A controlled pilot study. Eur J Clin Pharmacol 25: 323–324

    PubMed  Article  CAS  Google Scholar 

  43. Markkula J, Lauerma H (1997) Mianserin and restless legs. Int Clin Psychopharmacol 12: 53–58

    PubMed  Article  CAS  Google Scholar 

  44. McLean AJ (2004) The use of the dopamine-receptor partial agonist aripiprazole in the treatment of restless legs syndrome. Sleep 27: 1022

    PubMed  Google Scholar 

  45. Medicine A.A.o.S. (2005) International classification of sleep disorders, second edn: Diagnostic and coding manual edn. American Academy of Sleep Medicine

  46. Medicine A.A.o.S. (2001) International classification of slep disorders, revised: diagnostic and coding manual. American Academy of Sleep Medicine

  47. Mellick GA, Mellick LB (1996) Management of restless legs syndrome with gabapentin (Neurontin). Sleep 19: 224–226

    PubMed  CAS  Google Scholar 

  48. Micozkadioglu H, Ozdemir FN, Kut A et al. (2004) Gabapentin versus levodopa for the treatment of Restless Legs Syndrome in hemodialysis patients: an open-label study. Ren Fail 26: 393–397

    PubMed  Article  CAS  Google Scholar 

  49. Mitler MM, Browman CP, Menn SJ et al. (1986) Nocturnal myoclonus: treatment efficacy of clonazepam and temazepam. Sleep 9: 385–392

    PubMed  CAS  Google Scholar 

  50. Moldofsky H, Tullis C, Quance G, Lue FA (1986) Nitrazepam for periodic movements in sleep (sleep-related myoclonus). Can J Neurol Sci 13: 52–54

    PubMed  CAS  Google Scholar 

  51. Nofzinger EA, Fasiczka A, Berman S, Thase ME (2000) Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder. J Clin Psychiatry 61: 858–862

    PubMed  CAS  Google Scholar 

  52. Ohanna N, Peled R, Rubin AH et al. (1985) Periodic leg movements in sleep: effect of clonazepam treatment. Neurology 35: 408–411

    PubMed  Article  CAS  Google Scholar 

  53. Ozturk O, Eraslan D, Kumral E (2006) Oxcarbazepine treatment for paroxetine-induced restless leg syndrome. Gen Hosp Psychiatry 28: 264–265

    PubMed  Article  Google Scholar 

  54. Pae CU, Kim TS, Kim JJ et al. (2004) Re-administration of mirtazapine could overcome previous mirtazapine- associated restless legs syndrome? Psychiatry Clin Neurosci 58: 669–670

    PubMed  Article  CAS  Google Scholar 

  55. Page RL 2nd, Ruscin JM, Bainbridge JL, Brieke AA (2008) Restless legs syndrome induced by escitalopram: case report and review of the literature. Pharmacotherapy 28: 271–280

    PubMed  Article  CAS  Google Scholar 

  56. Paik IH, Lee C, Choi BM et al. (1989) Mianserin-induced restless legs syndrome. Br J Psychiatry 155: 415–417

    PubMed  CAS  Google Scholar 

  57. Perez Bravo A (2004) Utilidad del topiramato en el tratamiento del sindrome de piernas inquietas. Actas Esp Psiquiatr 32: 132–137

    Google Scholar 

  58. Perroud N, Lazignac C, Baleydier B et al. (2007) Restless legs syndrome induced by citalopram: a psychiatric emergency? Gen Hosp Psychiatry 29: 72–74

    PubMed  Article  Google Scholar 

  59. Picchietti D, Winkelman JW (2005) Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep 28: 891–898

    PubMed  Google Scholar 

  60. Pinninti NR, Mago R, Townsend J, Doghramji K (2005) Periodic restless legs syndrome associated with quetiapine use: a case report. J Clin Psychopharmacol 25: 617–618

    PubMed  Article  Google Scholar 

  61. Prospero-Garcia KA, Torres-Ruiz A, Ramirez-Bermudez J et al. (2006) Fluoxetine-mirtazapine interaction may induce restless legs syndrome: report of 3 cases from a clinical trial. J Clin Psychiatry 67: 1820

    PubMed  Google Scholar 

  62. Read DJ, Feest TG, Nassim MA (1981) Clonazepam: effective treatment for restless legs syndrome in uraemia. Br Med J (Clin Res Ed) 283: 885–886

    Google Scholar 

  63. Romigi A, Izzi F, Placidi F et al. (2007) Topiramate-induced restless legs syndrome: A report of two cases. J Neurol 254: 1120–1121

    PubMed  Article  Google Scholar 

  64. Saletu M, Anderer P, Saletu-Zyhlarz G et al. (2001) Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol 11: 153–161

    PubMed  Article  CAS  Google Scholar 

  65. Saletu-Zyhlarz GM, Abu-Bakr MH, Anderer P et al. (2002) Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Prog Neuropsychopharmacol Biol Psychiatry 26: 249–260

    PubMed  Article  CAS  Google Scholar 

  66. Salin-Pascual RJ, Galicia-Polo L, Drucker-Colin R (1997) Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 58: 348–350

    PubMed  CAS  Google Scholar 

  67. Sandyk R, Iacono RP, Bamford CR (1988) Spinal cord mechanisms in amitriptyline responsive restless legs syndrome in Parkinson’s disease. Int J Neurosci 38: 121–124

    PubMed  Article  CAS  Google Scholar 

  68. Sanz-Fuentenebro FJ, Huidobro A, Tejadas-Rivas A (1996) Restless legs syndrome and paroxetine. Acta Psychiatr Scand 94: 482–484

    PubMed  Article  CAS  Google Scholar 

  69. Scharf MB, Brown L, Hirschowitz J (1986) Possible efficacy of alprazolam in restless leg syndrome. Hillside J Clin Psychiatry 8: 214–223

    PubMed  CAS  Google Scholar 

  70. Schenck CH, Mahowald MW (1996) Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Med 100: 333–337

    PubMed  Article  CAS  Google Scholar 

  71. Scherbaum N, Stuper B, Bonnet U, Gastpar M (2003) Transient restless legs-like syndrome as a complication of opiate withdrawal. Pharmacopsychiatry 36: 70–72

    PubMed  Article  CAS  Google Scholar 

  72. Staedt J, Dewes D, Danos P, Stoppe G (2000) Can chronic neuroleptic treatment promote sleep disturbances in elderly schizophrenic patients? Int J Geriatr Psychiatry 15: 170–176

    PubMed  Article  CAS  Google Scholar 

  73. Staedt J, Stoppe G, Riemann H et al. (1996) Lamotrigine in the treatment of nocturnal myoclonus syndrome (NMS): two case reports. J Neural Transm 103: 355–361

    PubMed  Article  CAS  Google Scholar 

  74. Teive HA, de Quadros A, Barros FC, Werneck LC (2002) Sindrome das pernas inquietas com heranca autossomica dominante piorada pelo uso de mirtazapina: relato de caso. Arq Neuropsiquiatr 60: 1025–1029

    PubMed  Google Scholar 

  75. Telstad W, Sorensen O, Larsen S et al. (1984) Treatment of the restless legs syndrome with carbamazepine: a double blind study. Br Med J (Clin Res Ed) 288: 444–446

    Google Scholar 

  76. Terao T, Terao M, Yoshimura R, Abe K (1991) Restless legs syndrome induced by lithium. Biol Psychiatry 30: 1167–1170

    PubMed  Article  CAS  Google Scholar 

  77. Thorp ML, Morris CD, Bagby SP (2001) A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients. Am J Kidney Dis 38: 104–108

    PubMed  Article  CAS  Google Scholar 

  78. Trenkwalder C, Paulus W, Walters AS (2005) The restless legs syndrome. Lancet Neurol 4: 465–475

    PubMed  Article  CAS  Google Scholar 

  79. Trenkwalder C.e.a. (2007) Leitlinie zur Diagnose und Therapie des Restless-Legs-Syndroms (RLS), Newsletter der Deutschen Gesellschaft für Neurologie, http://www.dgn.org/fileadmin/leit05/RLS_Sommer_2007.pdf

  80. Ulfberg J, Bjorvatn B, Leissner L et al. (2007) Comorbidity in restless legs syndrome among a sample of Swedish adults. Sleep Med 8: 768–772

    PubMed  Article  Google Scholar 

  81. Ware JC, Brown FW, Moorad PJ et al. (1984) Nocturnal myoclonus and tricyclic antidepressanats. Sleep Res 13: 72

    Google Scholar 

  82. Wetter TC, Brunner J, Bronisch T (2002) Restless legs syndrome probably induced by risperidone treatment. Pharmacopsychiatry 35: 109–111

    PubMed  Article  CAS  Google Scholar 

  83. Winkelmann J (2008) Genetics of restless legs syndrome. Curr Neurol Neurosci Rep 8: 211–216

    PubMed  Article  CAS  Google Scholar 

  84. Winkelmann J, Schadrack J, Wetter TC et al. (2001) Opioid and dopamine antagonist drug challenges in untreated restless legs syndrome patients. Sleep Med 2: 57–61

    PubMed  Article  Google Scholar 

  85. Yang C, White DP, Winkelman JW (2005) Antidepressants and periodic leg movements of sleep. Biol Psychiatry 58: 510–514

    PubMed  Article  CAS  Google Scholar 

  86. Youssef EA, Wagner ML, Martinez JO, Hening W (2005) Pilot trial of lamotrigine in the restless legs syndrome. Sleep Med 6: 89Zucconi M, Coccagna G, Petronelli R et al. (1989) Nocturnal myoclonus in restless legs syndrome effect of carbamazepine treatment. Funct Neurol 4: 263–271

    Google Scholar 

  87. Zucconi M, Coccagna G, Petronelli R et al. (1989) Nocturnal myoclonus in restless legs syndrome effect of carbamazepine treatment. Funct Neurol 4: 263–271

    PubMed  CAS  Google Scholar 

  88. Cohrs S, Meier A, Neumann AC et al. (2005) Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy malesubjects. J Clin Psychiatry 66: 989–96

    PubMed  CAS  Article  Google Scholar 

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Cohrs, S., Rodenbeck, A., Hornyak, M. et al. Restless-legs-Syndrom, periodische Gliedmaßenbewegungen im Schlaf und Psychopharmakologie. Nervenarzt 79, 1263–1272 (2008). https://doi.org/10.1007/s00115-008-2575-2

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Schlüsselwörter

  • Restless-legs-Syndrom
  • Syndrom der periodischen Gliedmaßenbewegungen
  • Schlaf
  • Psychopharmakologie
  • Antidepressiva

Keywords

  • Restless legs syndrome
  • Periodic limb movement disorder
  • Psychopharmacology
  • Sleep
  • Antidepressants