CNS Drugs

, Volume 24, Issue 2, pp 119–129

Oral and Infusion Levodopa-Based Strategies for Managing Motor Complications in Patients with Parkinson’s Disease

  • Angelo Antonini
  • K. Ray Chaudhuri
  • Pablo Martinez-Martin
  • Per Odin
Review Article
  • 139 Downloads

Abstract

Levodopa is the most effective treatment for Parkinson’s disease (PD) signs and symptoms, and patients invariably will require it during the course of the disease. It also provides benefits in activities of daily living, quality of life and life expectancy. However, after a few years of levodopa treatment the majority of patients will experience motor fluctuations and dyskinesia. Initial use of a dopamine receptor agonist may delay the emergence of motor fluctuations but at the cost of reduced symptomatic control compared with the use of levodopa in some cases. Adequate management of motor fluctuations and dyskinesia is essential to maintaining satisfactory quality of life at the advanced stage of disease. Various levodopa-based strategies are currently available that aim to control motor complications (wearing-off and dyskinesia) in PD and each approach has its own unique benefit and risk profile. Strategies such as dose fragmentation (smaller, more frequent dosing) or the use of orally administered, liquid levodopa formulations or melevodopa can reduce off-time intervals or facilitate absorption. More recently introduced, continuous delivery of dopaminergic medications may represent a more effective approach to treat motor complications in advanced PD and its effect can be perceived from improvement in clinical scales, as well as in health-related items. Indeed, continuous levodopa delivery by duodenal infusion may stabilize and significantly improve motor function as well as patients’ quality of life. We propose a treatment algorithm that takes into account all currently available levodopa-based treatment strategies for motor complications in patients with PD.

References

  1. 1.
    Ehringer H, Hornykiewicz O. Distribution of noradrena-line and dopamine (3-hydroxytyramine) in the human brain and their behaviour in diseases of the extrapyramidal system [in German]. Klin Wochenschr 1960; 38: 1236–9PubMedCrossRefGoogle Scholar
  2. 2.
    Agid Y, Ahlshog E, Albanese A, et al. Levodopa in the treatment of Parkinson’s disease: a consensus meeting. Mov Disord 1995; 14: 911–3CrossRefGoogle Scholar
  3. 3.
    Rascol O, Goetz C, Koller W, et al. Treatment interventions for Parkinson’s disease: an evidence based assessment. Lancet 2002; 359: 1589–98PubMedCrossRefGoogle Scholar
  4. 4.
    Rajput AH. Levodopa prolongs life expectancy and is non-toxic to substantia nigra. Parkinsonism Related Dis 2001; 8: 95–100CrossRefGoogle Scholar
  5. 5.
    Nutt JG, Holford NHG. The response to levodopa in Parkinson’s disease: imposing pharmacological law and order. Ann Neurol 1996; 39: 561–73PubMedCrossRefGoogle Scholar
  6. 6.
    Obeso JA, Grandas F, Vaamonde J, et al. Motor complications associated with chronic levodopa therapy in Parkinson’s disease. Neurology 1989; 39 Suppl. 2: 11–9Google Scholar
  7. 7.
    Marsden CD, Parkes JD, Quinn N. Fluctuations disability in Parkinson’s disease: clinical aspects. In: Masden CD, Fahn S, editors. Movement disorders. London: Butter-worth, 1982: 96–122Google Scholar
  8. 8.
    Grandas F, Luquin MR, Rodriguez M, et al. Motor fluctuations in Parkinson disease: risk factors. Neurologia 1992; 7: 89–93PubMedGoogle Scholar
  9. 9.
    Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson’s disease: a community-based study. Brain 2000; 123: 2297–305PubMedCrossRefGoogle Scholar
  10. 10.
    Chapuis S, Ouchchane L, Metz O, et al. Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord 2005; 20: 224–30PubMedCrossRefGoogle Scholar
  11. 11.
    Lloyd KG, Davison L, Hornykiewicz O. The neurochemistry of Parkinson’s disease: effect of L-dopa therapy. J Pharmacol Exp Ther 1975; 195: 453–64PubMedGoogle Scholar
  12. 12.
    Tolosa E, Martin WE, Cohen HP, et al. Patterns of clinical response on plasma dopa levels in Parkinson’s disease. Neurology 1975; 25: 177–83PubMedCrossRefGoogle Scholar
  13. 13.
    Kurlan R, Rothfield KP, Woodward WR, et al. Erratic gastric emptying may cause “random” fluctuations of parkinsonian mobility. Neurology 1988; 38: 419–21PubMedCrossRefGoogle Scholar
  14. 14.
    Kurlan R, Nutt JG, Woodward WR, et al. Duodenal and gastric delivery of levodopa in Parkinsonism. Ann Neurol 1988; 23: 589–95PubMedCrossRefGoogle Scholar
  15. 15.
    Nutt JG, Woodward WR, Hammerstad JP, et al. The “on-off” phenomenon in Parkinson’s disease: relation to levodopa absorption and transport. N Engl J Med 1984; 310: 483–8PubMedCrossRefGoogle Scholar
  16. 16.
    Tsui JK, Ross S, Poulin K, et al. The effect of dietary protein on the efficacy of levodopa: a double-blind study. Neurology 1989; 39: 549–52PubMedCrossRefGoogle Scholar
  17. 17.
    Grandas F, Galiano MF, Tabernero C. Risk factors for levodopa-induced dyskinesia in Parkinson’s disease. J Neurol 1999; 246: 1127–33PubMedCrossRefGoogle Scholar
  18. 18.
    Kuoppamäki M, Korpela K, Marttila R, et al. Comparisonof pharmacokinetic profile of levodopa throughout the day between levodopa/carbidopa/entacapone and levodopa/ carbidopa when administered four or five times daily. Eur J Clin Pharmacol 2009; 65: 443–55PubMedCrossRefGoogle Scholar
  19. 19.
    Olanow CW, Obeso JA, Stocchi F. Drug insight: continuous dopaminergic stimulation in the treatment of Parkinson’s disease. Nat Clin Pract Neurol 2006; 2: 382–92PubMedCrossRefGoogle Scholar
  20. 20.
    Obeso JA, Rodriguez-Oroz MC, Marin C, et al. The origin of motor fluctuations in Parkinson’s disease: importance of dopaminergic innervations and basal ganglia circuits. Neurology 2004; 62Suppl. 1: S17–30PubMedCrossRefGoogle Scholar
  21. 21.
    Wolters ECh. Deep brain stimulation and continuous dopaminergic stimulation in advanced Parkinson’s disease. Parkinsonism Relat Disord 2007; 13 Suppl.: S18–23PubMedCrossRefGoogle Scholar
  22. 22.
    Wolters E, Lees AJ, Volkmann J, et al. Managing Parkinson’s disease with continuous dopaminergic stimulation. CNS Spectr 2008; 13(4 Suppl. 7): 1–14Google Scholar
  23. 23.
    Olanow CW, Obeso JA, Stocchi F. Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol 2006; 5: 677–87PubMedCrossRefGoogle Scholar
  24. 24.
    Stowe RL, Ives NJ, Clarke C, et al. Dopamine agonist therapy in early Parkinson’s disease. Cochrane Database Syst Rev 2008; (2): CD006564Google Scholar
  25. 25.
    Stocchi F. The levodopa wearing-off phenomenon in Parkinson’s disease: pharmacokinetic considerations.Expert Opin Pharmacother 2006; 7: 1399–407PubMedCrossRefGoogle Scholar
  26. 26.
    Koller WC, Hutton JT, Tolosa E, et al. Immediate releaseand controlled-release carbidopa/levodopa in PD: a 5-year randomized multicenter study. Carbidopa/Levodopa Study Group. Neurology 1999; 53: 1012–9Google Scholar
  27. 27.
    Stocchi F, Olanow CW. Continuous dopaminergic stimulation in early and advanced Parkinson’s disease. Neurology 2004; 62Suppl. 1: S56–63PubMedCrossRefGoogle Scholar
  28. 28.
    Pfeiffer RF. A promising new technology for Parkinson’s disease. Neurology 2005; 65(2 Suppl. 1): S6–10PubMedCrossRefGoogle Scholar
  29. 29.
    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: 956–63CrossRefGoogle Scholar
  30. 30.
    Hariz MI. Complications of deep brain stimulation surgery. Mov Disord 2002; 17Suppl. 3: S162–6PubMedCrossRefGoogle Scholar
  31. 31.
    Verhagen Metman L, Hoff J, Mouradian MM, et al. Fluctuationsin plasma levodopa and motor responses with liquid andtablet levodopa/carbidopa. Mov Disord 1994; 9: 463–5CrossRefGoogle Scholar
  32. 32.
    Stocchi F, Barbato L, Bramante L, et al. The clinical efficacy of a single afternoon dose of levodopa methyl ester: a double-blind cross-over study versus placebo. Funct Neurol 1994; 9: 259–64PubMedGoogle Scholar
  33. 33.
    Zangaglia R, Stocchi F, Sciarretta M, et al. Clinical experiences with levodopa methylester (melevodopa) in patients with Parkinson disease experiencing motor fluctuations: an open-label observational study. Clin Neuropharmacol. Epub 2009 Nov 21Google Scholar
  34. 34.
    Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol 2003; 2: 107–16PubMedCrossRefGoogle Scholar
  35. 35.
    Nyholm D, Lennernäs H. Irregular gastrointestinal drug absorption in Parkinson’s disease. Expert Opin Drug Metab Toxicol 2008; 4: 193–203PubMedCrossRefGoogle Scholar
  36. 36.
    Müller T, Erdmann C, Bremen D, et al. Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients. Clin Neuropharmacol 2006; 29: 61–7PubMedCrossRefGoogle Scholar
  37. 37.
    Goetze O, Wieczorek J, Mueller T, et al. Impaired gastric emptying of a solid test meal in patients with Parkinson’s disease using 13C-sodium octanoate breath test. Neurosci Lett 2005; 375: 170–3PubMedCrossRefGoogle Scholar
  38. 38.
    Pierantozzi M, Pietroiusti A, Brusa L, et al. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology 2006; 66: 1824–9PubMedCrossRefGoogle Scholar
  39. 39.
    Goetze O, Nikodem AB, Wiezcorek J, et al. Predictors of gastric emptying in Parkinson’s disease. Neurogastro-enterol Motil 2006; 18: 369–75CrossRefGoogle Scholar
  40. 40.
    Stocchi F, Fabbri L, Vecsei L, et al. Clinical efficacy of a single afternoon dose of effervescent levodopa-carbidopa preparation (CHF 1512) in fluctuating Parkinson disease. Clin Neuropharmacol 2007; 30: 18–24PubMedCrossRefGoogle Scholar
  41. 41.
    Data on file, Chiesi Pharmaceuticals, 2002Google Scholar
  42. 42.
    Hardoff R, Sula M, Tamir A, et al. Gastric emptying time and gastric motility in patients with Parkinson’s disease. Mov Disord 2001; 16: 1041–7PubMedCrossRefGoogle Scholar
  43. 43.
    Djaldetti R, Giladi N, Hassin-Baer S, et al. Pharmacokinetics of etilevodopa compared to levodopa in patients with Parkinson’s disease: an open-label, randomized, crossover study. Clin Neuropharmacol 2003; 26: 322–6PubMedCrossRefGoogle Scholar
  44. 44.
    LeWitt PA, Jennings D, Lyons KE, et al. Pharmacokinetic-pharmacodynamic crossover comparison of two levodopa extension strategies. Mov Disord 2009; 24: 1319–24PubMedCrossRefGoogle Scholar
  45. 45.
    Cedarbaum JM. The promise and limitations of controlled-release oral levodopa administration. Clin Neuropharmacol 1989; 12: 147–66PubMedCrossRefGoogle Scholar
  46. 46.
    Shoulson I, Glaubiger GA, Chase TN. On-off response: clinical and biochemical correlations during oral and intravenous levodopa administration in parkinsonian patients. Neurology 1975; 25: 1144–8PubMedCrossRefGoogle Scholar
  47. 47.
    Hardie RJ, Lees AJ, Stern GM. On-off fluctuations in Parkinson’s disease: a clinical and neuropharmacological study. Brain 1984; 107: 487–506PubMedCrossRefGoogle Scholar
  48. 48.
    Sage JI, Sonsalla PK, McHale DM, et al. Clinical experience with duodenal infusions of levodopa for the treatment of motor fluctuations in Parkinson’s disease. Adv Neurol 1990; 53: 383–6PubMedGoogle Scholar
  49. 49.
    Nyholm D. Enteral levodopa/carbidopa gel infusion for the treatment of motor fluctuations and dyskinesias in advanced Parkinson’s disease. Expert Rev Neurother 2006; 6: 1403–11PubMedCrossRefGoogle Scholar
  50. 50.
    Samanta J, Hauser RA. Duodenal levodopa infusion for thetreatment of Parkinson’s disease. Expert Opin Pharmacother 2007; 8: 657–64PubMedCrossRefGoogle Scholar
  51. 51.
    Nyholm D, Nilsson Remahl AI, Dizdar N, et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology 2005; 64: 216–23PubMedCrossRefGoogle Scholar
  52. 52.
    Lee MA, Walker RW, Hildreth AJ, et al. Individualized assessment of quality of life in idiopathic Parkinson’s disease. Mov Disord 2006; 21: 1929–34PubMedCrossRefGoogle Scholar
  53. 53.
    Antonini A, Isaias IU, Canesi M, et al. Duodenal levodopa infusion for advanced Parkinson’s disease: 12-month treatment outcome. Mov Disord 2007 15; 22: 1145–9PubMedCrossRefGoogle Scholar
  54. 54.
    Nilsson D, Nyholm D, Aquilonius SM. Duodenal levodopa infusion in Parkinson’s disease: long-term experience. Acta Neurol Scand 2001; 104: 343–8PubMedCrossRefGoogle Scholar
  55. 55.
    Antonini A, Tolosa E. Apomorphine and levodopa infusion therapies for advanced Parkinson’s disease: selection criteria and patient management. Expert Rev Neurother 2009; 9: 859–67PubMedCrossRefGoogle Scholar
  56. 56.
    Pietz K, Hagell P, Odin P. Subcutaneous apomorphine in late stage Parkinson’s disease: a long term follow up. J Neurol Neurosurg Psychiatry 1998; 65: 709–16PubMedCrossRefGoogle Scholar
  57. 57.
    Di Rosa AE, Epifanio A, Antonini A, et al. Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson’s disease. Neurol Sci 2003; 24: 174–5PubMedCrossRefGoogle Scholar
  58. 58.
    Poewe WH, Rascol O, Quinn N, et al. Efficacy of prami-pexole and transdermal rotigotine in advanced Parkinson’s disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurol 2007; 6: 513–20PubMedCrossRefGoogle Scholar
  59. 59.
    Rascol O, Brooks DJ, Melamed E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005; 365: 947–54PubMedCrossRefGoogle Scholar
  60. 60.
    Antonini A. Continuous dopaminergic stimulation: from theory to clinical practice. Parkinsonism Relat Disord 2007; 13 Suppl.: S24–8PubMedCrossRefGoogle Scholar
  61. 61.
    Antonini A, Tolosa E, Mizuno Y, et al. A reassessment of risks and benefits of dopamine agonists in Parkinson’s disease. Lancet Neurol 2009; 8: 929–37PubMedCrossRefGoogle Scholar
  62. 62.
    DeGaspari D, Siri C, Landi A, et al. Clinical and neuro-psychological follow up at 12 months in patients with complicated Parkinson’s disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus. J Neurol Neurosurg Psychiat 2006; 77: 450–3CrossRefGoogle Scholar
  63. 63.
    Derost PP, Ouchchane L, Morand D, et al. Is DBS-STN appropriate to treat severe Parkinson disease in an elderly population? Neurology 2007; 68: 1345–55PubMedCrossRefGoogle Scholar
  64. 64.
    Lees AJ. Alternatives to levodopa in the initial treatment of early Parkinson’s disease. Drugs Aging 2005; 22: 731–40PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Angelo Antonini
    • 1
  • K. Ray Chaudhuri
    • 2
  • Pablo Martinez-Martin
    • 3
  • Per Odin
    • 4
  1. 1.IRCCS, San CamilloVeniceItaly
  2. 2.Kings College and Institute of PsychiatryKings College Hospital and University Hospital LewishamLondonUK
  3. 3.National Center for Epidemiology and CIBERNEDCarlos III Institute of HealthMadridSpain
  4. 4.Department of NeurologyKlinikum-BremerhavenBremenGermany

Personalised recommendations