Current Neurology and Neuroscience Reports

, Volume 7, Issue 4, pp 302–310

Levodopa-induced Dyskinesia in Parkinson’s disease: Epidemiology, etiology, and treatment

  • Theresa A. Zesiewicz
  • Kelly L. Sullivan
  • Robert A. Hauser


Although levodopa is the gold standard for treating motor symptoms of Parkinson’s disease (PD), long-term therapy leads to levodopa-induced dyskinesia (LID). Dyskinesia refers to involuntary movements other than tremor and most commonly consists of chorea that occurs when levodopa-derived dopamine is peaking in the brain (“peak-dose dyskinesia”). However, dyskinesia can also consist of dystonia or myoclonus and occur during other parts of the levodopa dosing cycle. New validated rating scales and home diaries can better help the health care provider assess the timing and severity of dyskinesia. The exact etiology of LID is unknown, but there is evidence that abnormal pulsatile stimulation of dopamine receptors may be contributory. Treatment of LID includes adjustment of PD medications to maximize “on” time without troublesome dyskinesia. Amantadine is the only medication available with demonstrated ability to reduce the expression of established LID without reducing antiparkinsonian benefit. Other medications that are currently being studied to treat established LID include antiepileptics and serotonergic medications. Deep brain stimulation of the subthalamic nucleus is now the most commonly used surgical procedure for PD patients, and it is very effective in treating LID.


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References and Recommended Reading

  1. 1.
    Pechevis M, Clarke CE, Vieregge P, et al.; Trial Study Group: Effects of dyskinesias in Parkinson’s disease on quality of life and health-related costs: a prospective European study. Eur J Neurol 2005, 12:956–963.PubMedCrossRefGoogle Scholar
  2. 2.
    Muenter MD, Sharpless NS, Tyce GM, Darley FL: Patterns of dystonia (“I-D-I” and “D-I-D”) in response to L dopa therapy for Parkinson’s disease. Mayo Clin Proc 1977, 52:163–174.PubMedGoogle Scholar
  3. 3.
    Rascol O, Fabre N: Dyskinesia: L-dopa-induced and tardive dyskinesia. Clin Neuropharmacol 2001, 24:313–323.PubMedCrossRefGoogle Scholar
  4. 4.
    Klawans HL, Goetz C, Bergen D: Levodopa-induced myoclonus. Arch Neurol 1975, 32:330–334.PubMedGoogle Scholar
  5. 5.
    Vidailhet M, Bonnet AM, Marconi R: The phenomenology of L-dopa-induced dyskinesias in Parkinson’s disease. Mov Disord 1999, 14(Suppl 1):13–18.PubMedGoogle Scholar
  6. 6.
    Marconi R, Lefebvre-Caparros D, Bonnet AM, et al.: Levodopa-induced dyskinesias in Parkinson’s disease: phenomenology and pathophysiology. Mov Disord 1994, 9:2–12.PubMedCrossRefGoogle Scholar
  7. 7.
    Damiano AM, McGrath MM, William MK, et al.: Evaluation of a measurement strategy for Parkinson’s disease: assessing patient health-related quality of life. Qual Life Res 2000, 9:87–100.PubMedCrossRefGoogle Scholar
  8. 8.
    Schrag A, Quinn N: Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study. Brain 2000, 123:2297–2305.PubMedCrossRefGoogle Scholar
  9. 9.
    Olanow C W, Koller WC: An algorithm (decision tree) for the management of Parkinson’s disease: treatment guidelines. American Academy of Neurology. Neurology 1998, 50(3 Suppl 3):S1–S57.PubMedGoogle Scholar
  10. 10.
    Ahlskog JE, Muenter MD: Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 2001, 16:448–458.PubMedCrossRefGoogle Scholar
  11. 11.
    Van Gerpen JA, Kumar N, Bower JH, et al.: Levodop-associated dyskinesia risk among Parkinson disease patients in Olmsted County, Minnesota, 1976–1990. Arch Neurol 2006, 63:205–209.PubMedCrossRefGoogle Scholar
  12. 12.
    Fahn S, Oakes D, Shoulson I, et al.: Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004, 351:2498–2508.PubMedCrossRefGoogle Scholar
  13. 13.
    Rascol O, Brooks DJ, Korczyn AD, et al.; 056 Study Group: Development of dyskinesias in a 5-year trial of ropinirole and L-dopa. Mov Disord 2006, 21:1844–1850.PubMedCrossRefGoogle Scholar
  14. 14.
    Holloway RG, Shoulson I, Fahn S, et al.: Parkinson Study Group: Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol 2004, 61:1044–1053.PubMedCrossRefGoogle Scholar
  15. 15.
    Papapetropoulos S, Mash DC: Motor fluctuations and dyskinesias in advanced/end stage Parkinson’s disease: a study from a population of brain donors. J Neural Transm 2007, 114:341–345.PubMedCrossRefGoogle Scholar
  16. 16.
    Zappia M, Annesi G, Nicoletti G, et al.: Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease. Arch Neurol 2005, 62:601–605.PubMedCrossRefGoogle Scholar
  17. 17.
    Sharma JC, Macnamara L, Hasoon M, et al.: Cascade of levodopa dose and weight-related dyskinesia in Parkinson’s disease (LD-WD-PD cascade). Parkinsonism Relat Disord 2006, 12:499–505.PubMedCrossRefGoogle Scholar
  18. 18.
    Hauser RA, McDermott MP, Messing S: Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol 2006, 63:1756–1760.PubMedCrossRefGoogle Scholar
  19. 19.
    Guy W: ECDEU Assessment Manual for Psychopharmacology. Washington, DC: Government Printing Office; 1976.Google Scholar
  20. 20.
    Goetz CG, Stebbins GT, Shale HM, et al.: Utility of an objective dyskineisa rating scale for Parkinson’s disease: inter-and intrarater reliability assessment. Mov Disord 1994, 9:390–394.PubMedCrossRefGoogle Scholar
  21. 21.
    Hauser RA, Deckers F, Lehert P: Parkinson’s disease home diary: further validation and implications for clinical trials. Mov Disord 2004, 19:1409–1413.PubMedCrossRefGoogle Scholar
  22. 22.
    Hauser RA, Friedlander J, Zesiewicz TA, et al.: A home diary to assess functional status in patients with Parkinson’s disease with motor fluctuations and dyskinesia. Clin Neuropharmacol 2000, 23:75–81.PubMedCrossRefGoogle Scholar
  23. 23.
    Konitsiotis S, Blanchet PJ, Verhagen L, et al.: AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys. Neurology 2000, 54:1589–1595.PubMedGoogle Scholar
  24. 24.
    Rascol O, Arnulf I, Saint P, et al.: Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson’s disease. Mov Disord 2001, 16:708–713.PubMedCrossRefGoogle Scholar
  25. 25.
    Bibbiani F, Oh JD, Chase TN: Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology 2001, 57:1829–1834.PubMedGoogle Scholar
  26. 26.
    Oh JD, Bibbiani F, Chase TN: Quetiapine attenuates levodopa-induced motor complications in rodent and primate parkinsonian models. Exp Neurol 2002, 177:557–564.PubMedCrossRefGoogle Scholar
  27. 27.
    Olanow CW, Obeso JA, Stocchi F: Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol 2006, 5:677–687.PubMedCrossRefGoogle Scholar
  28. 28.
    da Silva-Junior EP, Braga-Neto P, Sueli Monte F, de Bruin VM: Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study. Parkinsonism Relat Disord 2005, 11:449–452.PubMedCrossRefGoogle Scholar
  29. 29.
    Thomas A, Iacono D, Luciano AL, et al.: Duration of amantadine benefit on dyskinesia of severe Parkinson’s disease. J Neurol Neurosurg Psychiatry 2004, 75:141–143.PubMedGoogle Scholar
  30. 30.
    Metman LV, Del Dotto P, LePoole K, et al.: Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol 1999, 56:1383–1386.PubMedCrossRefGoogle Scholar
  31. 31.
    Butzer JF, Silver DE, Sahs AL: Amantadine in Parkinson’s disease. A double-blind, placebo-controlled, crossover study with long-term follow-up. Neurology 1975, 25:603–606.PubMedGoogle Scholar
  32. 32.
    Verhagen Metman L, Del Dotto P, van den Munckhof P, et al.: Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology 1998, 50:1323–1326.PubMedGoogle Scholar
  33. 33.
    Nyholm D: Enteral levodopa/carbidopa gel infusion for the treatment of motor fluctuations and dyskinesias in advanced Parkinsons’s disease. Expert Rev Neurother 2006, 6:1403–1411PubMedCrossRefGoogle Scholar
  34. 34.
    Nyholm D, Askmark H, Gomes-Trolin C, et al.: Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets. Clin Neuropharmacol 2003, 26:156–163.PubMedCrossRefGoogle Scholar
  35. 35.
    Nyholm D, Nilsson Remahl AI, Dizdar N, et al.: Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 2005, 64:216–223.PubMedGoogle Scholar
  36. 36.
    Block G, Liss C, Reines S, et al.: Comparison of immediate-release and controlled release carbidopa/levodopa in Parkinson’s disease. A multicenter 5-year study. The CR First Study Group. Eur Neurol 1997, 37:23–27.PubMedGoogle Scholar
  37. 37.
    Storch A, Trenkwalder C, Oehlwein C, et al.: High-dose treatment with pergolide in Parkinson’s disease patients with motor fluctuations and dyskinesias. Parkinsonism Relat Disord 2005, 11:393–398.PubMedCrossRefGoogle Scholar
  38. 38.
    Kaakkola S, Wurtman RJ: Effects of catechol-O-methyl-transferase inhibitors and L-3,4-dihydroxyphenylalanine with or without carbidopa on extracellular dopamine in rat striatum. J Neurochem 1993, 60:137–144.PubMedCrossRefGoogle Scholar
  39. 39.
    Rinne UK, Gordin A, Teravainen H: COMT inhibition with entacapone in the treatment of Parkinson’s disease. Ann Neurol 1999, 80:491–494.Google Scholar
  40. 40.
    Theresa A, Zesiewicz TA, Lyons KE, et al.: Parkinson’s Disease: Questions and Answers, edn 5. Edited by Robert A. Hauser. West Palm Beach, Florida: Merit Publishing International; 2006.Google Scholar
  41. 41.
    Marin C, Aguilar E, Obeso JA: Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats. Mov Disord 2006, 21:646–653.PubMedCrossRefGoogle Scholar
  42. 42.
    Smith LA, Jackson MJ, Al-Barghouthy G, et al.: Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates. Mov Disord 2005, 20:306–314.PubMedCrossRefGoogle Scholar
  43. 43.
    Loscher W, Richter A: Piracetam and levetiracetam, two pyrrolidone derivatives, exert antidystonic activity in a hamster model of paroxysmal dystonia. Eur J Pharmacol 2000, 391:251–254.PubMedCrossRefGoogle Scholar
  44. 44.
    Hill MP, Bezard E, McGuire SG, et al.: Novel antiepileptic drug levetiracetam decreases dyskinesia elicited by L-dopa and ropinirole in the MPTP-lesioned marmoset. Mov Disord 2003, 18:1301–1305.PubMedCrossRefGoogle Scholar
  45. 45.
    Zesiewicz TA, Sullivan KL, Maldonado JL, et al.: Openlabel pilot study of levetiracetam (Keppra) for the treatment of levodopa-induced dyskinesias in Parkinson’s disease. Mov Disord 2005, 20:1205–1209.PubMedCrossRefGoogle Scholar
  46. 46.
    Lyons KE, Pahwa R: Efficacy and tolerability of levetiracetam in Parkinson disease patients with levodopa-induced dyskinesia. Clin Neuropharmacol 2006, 29:148–153.PubMedCrossRefGoogle Scholar
  47. 47.
    Iravani MM, Tayarani-Binazir K, Chu WB, et al.: In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with/increased motor disability. J Pharmacol Exp Ther 2006, 319:1225–1234.PubMedCrossRefGoogle Scholar
  48. 48.
    Goetz CG, Damier P, Hicking C, et al.: Sarizotan as a treatment for dyskinesias in Parkinson’s disease: a double-blind placebo-controlled trial. Mov Disord 2007, 22:179–186.PubMedCrossRefGoogle Scholar
  49. 49.
    Durif F, Debilly B, Galitzky M, et al.: Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study. Neurology 2004, 62:381–388.PubMedGoogle Scholar
  50. 50.
    Pierelli F, Adipietro A, Soldati G, et al.: Low dosage clozapine effects on L-dopa induced dyskinesias in parkinsonian patients. Acta Neurol Scand 1998, 97:295–299.PubMedGoogle Scholar
  51. 51.
    Bennett JP Jr, Landow ER, Dietrich S, Schuh LA: Suppression of dyskinesias in advanced Parkinson’s disease: moderate daily clozapine doses provide long-term dyskinesia reduction. Mov Disord 1994, 9:409–414.PubMedCrossRefGoogle Scholar
  52. 52.
    Samadi P, Gregoire L, Rouillard C, et al.: Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys. Ann Neurol 2006, 59:282–288.PubMedCrossRefGoogle Scholar
  53. 53.
    Verhagen Metman L, Blanchet PJ, van den Munckhof P, et al.: A trial of dextromethorphan in parkinsonian patients with motor response complications. Mov Disord 1998, 13:414–417.PubMedCrossRefGoogle Scholar
  54. 54.
    Verhagen Metman L, Del Dotto P, Natte R, et al.: Dextromethorphan improves levodopa-induced dyskinesias in Parkinson’s disease. Neurology 1998, 51:203–206.PubMedGoogle Scholar
  55. 55.
    Metman LV, O’Leary ST: Role of surgery in the treatment of motor complications. Mov Disord 2005, 20(Suppl 11):S45–56.PubMedCrossRefGoogle Scholar
  56. 56.
    Deep-Brain Stimulation for Parkinson’s Disease Study Group: Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med 2001, 345:956–963.CrossRefGoogle Scholar
  57. 57.
    Merello M, Nouzeilles MI, Kuzis G, et al.: Unilateral radiofrequency lesion versus electrostimulation of posteroventral pallidum: a prospective randomized comparison. Mov Disord 1999, 14:50–56.PubMedCrossRefGoogle Scholar
  58. 58.
    Ogura M, Nakao N, Nakai E, et al.: The mechanism and effect of chronic electrical stimulation of the globus pallidus for treatment of Parkinson disease. J Neurosurg 2004, 100:997–1001.PubMedGoogle Scholar
  59. 59.
    Alkhani A, Lozano AM: Pallidotomy for Parkinson’s disease: a review of contemporary literature. J Neurosurg 2001, 94:43–49.PubMedCrossRefGoogle Scholar
  60. 60.
    Vitek JL, Bakay RA, Freeman A, et al.: Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol 2003, 53:558–569.PubMedCrossRefGoogle Scholar
  61. 61.
    Kleiner-Fisman G, Herzog J, Fisman DN, et al.: Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord 2006, 21(Suppl 14):S290–304.PubMedCrossRefGoogle Scholar
  62. 62.
    Deuschl G, Schade-Brittinger C, Krack P; German Parkinson Study Group, Neurostimulation Section: A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 2006, 355:896–908.PubMedCrossRefGoogle Scholar
  63. 63.
    Ostergaard K, Sunde N, Dupont E: Effects of bilateral stimulation of the subthalamic nucleus in patients with severe Parkinson’s disease and motor fluctuations. Mov Disord 2002, 17:693–700.PubMedCrossRefGoogle Scholar
  64. 64.
    Pahwa R, Wilkinson SB, Overman J, Lyons KE: Bilateral subthalamic stimulation in patients with Parkinson disease: long-term follow up. J Neurosurg 2003, 99:71–77.PubMedGoogle Scholar
  65. 65.
    Esselink RA, de Bie RM, de Haan RJ, et al.: Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD: a randomized trial. Neurology 2004, 62:201–207.PubMedGoogle Scholar
  66. 66.
    Lang AE: Surgery for levodopa-induced dyskinesias. Ann Neurol 2000, 47(Suppl 1):S193–S199; discussion S199–S202.PubMedGoogle Scholar
  67. 67.
    Krack P, Batir A, Van Blercom N, et al.: Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 2003, 349:1925–1934.PubMedCrossRefGoogle Scholar
  68. 68.
    Freed CR, Greene PE, Breeze RE, et al.: Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001, 344:710–719.PubMedCrossRefGoogle Scholar
  69. 69.
    Olanow CW, Goetz CG, Kordower JH, et al.: A doubleblind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 2003, 54:403–414.PubMedCrossRefGoogle Scholar
  70. 70.
    Ma Y, Feigin A, Dhawan V, et al.: Dyskinesia after fetal cell transplantation for Parkinsonism: a PET study. Ann Neurol 2002, 52:628–634.PubMedCrossRefGoogle Scholar
  71. 71.
    Hagell P, Piccini P, Bjorkland A, et al.: Dyskinesias following neural transplantation in Parkinson’s disease. Nat Neurosci 2002, 5:627–628.PubMedGoogle Scholar
  72. 72.
    Young RF, Vermeulen S, Posewitz A, Shumway-Cook A: Pallidotomy with the gamma knife: a positive experience. Stereotact Funct Neurosurg 1998, 70(Suppl 1):218–228PubMedCrossRefGoogle Scholar
  73. 73.
    Grondin R, Zhand Z, Yi A, et al.: Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 2002, 125:2191–2201.PubMedCrossRefGoogle Scholar
  74. 74.
    Gill SS, Patel NK, Hotton GR, et al.: Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 2003, 9:589–595.PubMedCrossRefGoogle Scholar
  75. 75.
    Lang A E, Gill S, Patel NK, et al.: Randomized controlled trial of intraputamental glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 2006, 59:459–466.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  • Theresa A. Zesiewicz
    • 1
  • Kelly L. Sullivan
  • Robert A. Hauser
  1. 1.Parkinson’s Disease and Movement Disorders CenterUniversity of South FloridaTampaUSA

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