Skip to main content
SpringerLink
Log in

Management of Motor and Non-Motor Symptoms in Parkinson’s Disease

  • Therapy in Practice
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder that affects approximately 1 % of people over the age of 60 years. Accurate diagnosis and individualized assessment of the risks and benefits of available antiparkinsonian medications as well as specific clinical features and the phase of disease should guide treatment for patients with PD. Levodopa still remains the gold standard for the treatment of motor symptoms of PD but dopamine agonists (DAs), catechol-O-methyltransferase (COMT) inhibitors and monoamine oxidase B (MAO-B) inhibitors have also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to improve motor outcomes and decrease the risk of levodopa-induced motor complications. Deep-brain stimulation as well as other invasive therapies can be used for the treatment of drug-refractory levodopa-induced motor complications. Despite all of the therapeutic advances achieved within the last 20 years, PD continues to be a progressive disorder leading to severe disability caused by motor and non-motor symptoms. To date, neuroprotective interventions able to modify PD progression are not available. This review focuses on medical and invasive treatment strategies for early and advanced stages of PD as well as on the treatment of PD non-motor symptoms such as mood and behavioural disorders, cognitive and autonomic dysfunction, and sleep disorders, which can antedate PD motor symptoms for years.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, et al. Prevalence of Parkinson’s disease in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54(11 Suppl 5):S21–3.

    PubMed  Google Scholar 

  2. Rajput AH. Frequency and cause of Parkinson’s disease. Can J Neurol Sci. 1992;19(1 Suppl):103–7.

    PubMed  CAS  Google Scholar 

  3. Tanner CM, Goldman SM. Epidemiology of Parkinson’s disease. Neurol Clin. 1996;14(2):317–35.

    PubMed  CAS  Google Scholar 

  4. Forno LS. Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol. 1996;55(3):259–72.

    PubMed  CAS  Google Scholar 

  5. Takahashi H, Wakabayashi K. The cellular pathology of Parkinson’s disease. Neuropathology. 2001;21(4):315–22.

    PubMed  CAS  Google Scholar 

  6. Fox SH, Katzenschlager R, Lim SY, Ravina B, Seppi K, Coelho M, et al. The movement disorder society evidence-based medicine review update: treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 2011;26(Suppl 3):S2–41.

    PubMed  Google Scholar 

  7. Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, et al. The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov Disord. 2011;26(Suppl 3):S42–80.

    PubMed  Google Scholar 

  8. Yamamoto M. Practice guidelines for Parkinson’s disease. Parkinsonism Relat Disord. 2003;9(Suppl 2):S111–5.

    PubMed  Google Scholar 

  9. Weiner WJ. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines [letter]. Neurology. 2002;58(1):156 (author reply 156–7).

    Google Scholar 

  10. Olanow CW, 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):S1–57.

    PubMed  CAS  Google Scholar 

  11. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001;56(11 Suppl 5):S1–88.

    PubMed  CAS  Google Scholar 

  12. Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO study. Arch Neurol. 2002;59(12):1937–43.

    Google Scholar 

  13. Shoulson I. DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl and tocopherol antioxidative therapy of parkinsonism. Ann Neurol. 1998;44(3 Suppl 1):S160–6.

    Google Scholar 

  14. Parkinson Study Group. DATATOP: a multicenter controlled clinical trial in early Parkinson’s disease. Arch Neurol. 1989;46(10):1052–60.

    Google Scholar 

  15. Olanow CW, Hauser RA, Jankovic J, Langston W, Lang A, Poewe W, et al. A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson’s disease (the ADAGIO study): rationale, design, and baseline characteristics. Mov Disord. 2008;23(15):2194–201.

    PubMed  Google Scholar 

  16. Wimbiscus M, Kostenko O, Malone D. MAO inhibitors: risks, benefits, and lore. Cleve Clin J Med. 2010;77(12):859–82.

    PubMed  Google Scholar 

  17. Richard IH, Kurlan R. A survey of antidepressant drug use in Parkinson’s disease. Parkinson Study Group. Neurology. 1997;49(4):1168–70.

    PubMed  CAS  Google Scholar 

  18. Hauser RA, Rascol O, Korczyn AD, Jon Stoessl A, Watts RL, Poewe W, et al. Ten-year follow-up of Parkinson’s disease patients randomized to initial therapy with ropinirole or levodopa. Mov Disord. 2007;22(16):2409–17.

    PubMed  Google Scholar 

  19. Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE. A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. 056 Study Group. N Engl J Med. 2000;342(20):1484–91.

    PubMed  CAS  Google Scholar 

  20. Potenza MN, Voon V, Weintraub D. Drug insight: impulse control disorders and dopamine therapies in Parkinson’s disease. Nat Clin Pract Neurol. 2007;3(12):664–72.

    PubMed  CAS  Google Scholar 

  21. Voon V, Potenza MN, Thomsen T. Medication-related impulse control and repetitive behaviors in Parkinson’s disease. Curr Opin Neurol. 2007;20(4):484–92.

    PubMed  Google Scholar 

  22. Weintraub D. Impulse control disorders in Parkinson’s disease: prevalence and possible risk factors. Parkinsonism Relat Disord. 2009;15(Suppl 3):S110–3.

    PubMed  Google Scholar 

  23. Holloway RG, Shoulson I, Fahn S, Kieburtz K, Lang A, Marek K, et al. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol. 2004;61(7):1044–53.

    PubMed  Google Scholar 

  24. Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson’s disease: a community-based study. Brain. 2000;123(Pt 11):2297–305.

    PubMed  Google Scholar 

  25. Fahn S. Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs Later L-DOPA. Arch Neurol. 1999;56(5):529–35.

    PubMed  CAS  Google Scholar 

  26. Hauser RA. IPX066: a novel carbidopa-levodopa extended-release formulation. Expert Rev Neurother. 2012;12(2):133–40.

    PubMed  CAS  Google Scholar 

  27. Ahlskog JE, Muenter MD, McManis PG, Bell GN, Bailey PA. Controlled-release Sinemet (CR-4): a double-blind crossover study in patients with fluctuating Parkinson’s disease. Mayo Clin Proc. 1988;63(9):876–86.

    PubMed  CAS  Google Scholar 

  28. Jankovic J, Schwartz K, Vander Linden C. Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations. Mov Disord. 1989;4(4):303–9.

    PubMed  CAS  Google Scholar 

  29. Stocchi F, Rascol O, Kieburtz K, Poewe W, Jankovic J, Tolosa E, et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol. 2010;68(1):18–27.

    PubMed  CAS  Google Scholar 

  30. Evans AH, Katzenschlager R, Paviour D, O’Sullivan JD, Appel S, Lawrence AD, et al. Punding in Parkinson’s disease: its relation to the dopamine dysregulation syndrome. Mov Disord. 2004;19(4):397–405.

    PubMed  Google Scholar 

  31. Kurlan R. Disabling repetitive behaviors in Parkinson’s disease. Mov Disord. 2004;19(4):433–7.

    PubMed  Google Scholar 

  32. Giovannoni G, O’Sullivan JD, Turner K, Manson AJ, Lees AJ. Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry. 2000;68(4):423–8.

    PubMed  CAS  Google Scholar 

  33. Lewitt PA. Levodopa for the treatment of Parkinson’s disease. N Engl J Med. 2008;359(23):2468–76.

    PubMed  CAS  Google Scholar 

  34. Gottwald MD, Aminoff MJ. Therapies for dopaminergic-induced dyskinesias in Parkinson disease. Ann Neurol. 2011;69(6):919–27.

    PubMed  CAS  Google Scholar 

  35. Leenders KL, Poewe WH, Palmer AJ, Brenton DP, Frackowiak RS. Inhibition of L-[18F]fluorodopa uptake into human brain by amino acids demonstrated by positron emission tomography. Ann Neurol. 1986;20(2):258–62.

    PubMed  CAS  Google Scholar 

  36. Hametner E, Seppi K, Poewe W. The clinical spectrum of levodopa-induced motor complications. J Neurol. 2010;257(Suppl 2):S268–75.

    PubMed  CAS  Google Scholar 

  37. de la Fuente-Fernandez R, Schulzer M, Mak E, Calne DB, Stoessl AJ. Presynaptic mechanisms of motor fluctuations in Parkinson’s disease: a probabilistic model. Brain. 2004;127(Pt 4):888–99.

    PubMed  Google Scholar 

  38. Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, 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(9463):947–54.

    PubMed  CAS  Google Scholar 

  39. Hauser RA, Ellenbogen AL, Metman LV, Hsu A, O’Connell MJ, Modi NB, et al. Crossover comparison of IPX066 and a standard levodopa formulation in advanced Parkinson’s disease. Mov Disord. 2011;26(12):2246–52.

    PubMed  Google Scholar 

  40. Pahwa R, Stacy MA, Factor SA, Lyons KE, Stocchi F, Hersh BP, et al. Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease. Neurology. 2007;68(14):1108–15.

    PubMed  CAS  Google Scholar 

  41. Poewe WH, Rascol O, Quinn N, Tolosa E, Oertel WH, Martignoni E, et al. Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson’s disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurol. 2007;6(6):513–20.

    PubMed  CAS  Google Scholar 

  42. Moller JC, Oertel WH, Koster J, Pezzoli G, Provinciali L. Long-term efficacy and safety of pramipexole in advanced Parkinson’s disease: results from a European multicenter trial. Mov Disord. 2005;20(5):602–10.

    PubMed  Google Scholar 

  43. Mizuno Y, Abe T, Hasegawa K, Kuno S, Kondo T, Yamamoto M, et al. Ropinirole is effective on motor function when used as an adjunct to levodopa in Parkinson’s disease: STRONG study. Mov Disord. 2007;22(13):1860–5.

    PubMed  Google Scholar 

  44. Barone P, Lamb J, Ellis A, Clarke Z. Sumanirole versus placebo or ropinirole for the adjunctive treatment of patients with advanced Parkinson’s disease. Mov Disord. 2007;22(4):483–9.

    PubMed  Google Scholar 

  45. LeWitt PA, Lyons KE, Pahwa R. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER study. Neurology. 2007;68(16):1262–7.

    PubMed  CAS  Google Scholar 

  46. Poewe W, Rascol O, Barone P, Hauser RA, Mizuno Y, Haaksma M, et al. Extended-release pramipexole in early Parkinson disease: a 33-week randomized controlled trial. Neurology. 2011;77(8):759–66.

    PubMed  CAS  Google Scholar 

  47. Schapira AH, Barone P, Hauser RA, Mizuno Y, Rascol O, Busse M, et al. Extended-release pramipexole in advanced Parkinson disease: a randomized controlled trial. Neurology. 2011;77(8):767–74.

    PubMed  CAS  Google Scholar 

  48. Stocchi F, Giorgi L, Hunter B, Schapira AH. PREPARED: comparison of prolonged and immediate release ropinirole in advanced Parkinson’s disease. Mov Disord. 2011;26(7):1259–65.

    PubMed  Google Scholar 

  49. Grosset D. Dopamine agonists and therapy compliance. Neurol Sci. 2008;29(Suppl 5):S375–6.

    PubMed  Google Scholar 

  50. Ondo W, Hunter C, Almaguer M, Gancher S, Jankovic J. Efficacy and tolerability of a novel sublingual apomorphine preparation in patients with fluctuating Parkinson’s disease. Clin Neuropharmacol. 1999;22(1):1–4.

    PubMed  CAS  Google Scholar 

  51. Poewe W, Wenning GK. Apomorphine: an underutilized therapy for Parkinson’s disease. Mov Disord. 2000;15(5):789–94.

    PubMed  CAS  Google Scholar 

  52. Katzenschlager R, Hughes A, Evans A, Manson AJ, Hoffman M, Swinn L, et al. Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson’s disease: a prospective study using single-dose challenges. Mov Disord. 2005;20(2):151–7.

    PubMed  Google Scholar 

  53. Tyne HL, Parsons J, Sinnott A, Fox SH, Fletcher NA, Steiger MJ. A 10 year retrospective audit of long-term apomorphine use in Parkinson’s disease. J Neurol. 2004;251(11):1370–4.

    PubMed  Google Scholar 

  54. Dewey RB Jr, Hutton JT, LeWitt PA, Factor SA. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events. Arch Neurol. 2001;58(9):1385–92.

    PubMed  Google Scholar 

  55. Nyholm D, Nilsson Remahl AI, Dizdar N, Constantinescu R, Holmberg B, Jansson R, et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology. 2005;64(2):216–23.

    PubMed  CAS  Google Scholar 

  56. Antonini A, Isaias IU, Canesi M, Zibetti M, Mancini F, Manfredi L, et al. Duodenal levodopa infusion for advanced Parkinson’s disease: 12-month treatment outcome. Mov Disord. 2007;22(8):1145–9.

    PubMed  Google Scholar 

  57. Devos D. Patient profile, indications, efficacy and safety of duodenal levodopa infusion in advanced Parkinson’s disease. Mov Disord. 2009;24(7):993–1000.

    PubMed  Google Scholar 

  58. Santos-Garcia D, Macias M, Llaneza M, Grande M, de la Fuente-Fernandez R. Serum vitamin B(12) and folate levels in Parkinson’s disease patients treated with duodenal levodopa infusion. Mov Disord. 2011;26(3):558–9.

    PubMed  Google Scholar 

  59. Weaver FM, Follett KA, Stern M, Luo P, Harris CL, Hur K, et al. Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes. Neurology. 2012;79(1):55–65.

    PubMed  CAS  Google Scholar 

  60. Harries AM, Kausar J, Roberts SA, Mocroft AP, Hodson JA, Pall HS, et al. Deep brain stimulation of the subthalamic nucleus for advanced Parkinson disease using general anesthesia: long-term results. J Neurosurg. 2012;116(1):107–13.

    PubMed  Google Scholar 

  61. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355(9):896–908.

    PubMed  CAS  Google Scholar 

  62. Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301(1):63–73.

    PubMed  CAS  Google Scholar 

  63. Castrioto A, Lozano AM, Poon YY, Lang AE, Fallis M, Moro E. Ten-year outcome of subthalamic stimulation in Parkinson disease: a blinded evaluation. Arch Neurol. 2011;68(12):1550–6.

    PubMed  Google Scholar 

  64. Follett KA, Weaver FM, Stern M, Hur K, Harris CL, Luo P, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2010;362(22):2077–91.

    PubMed  CAS  Google Scholar 

  65. Volkmann J. Deep brain stimulation for Parkinson’s disease. Parkinsonism Relat Disord. 2007;13(Suppl 3):S462–5.

    PubMed  Google Scholar 

  66. Voges J, Hilker R, Botzel K, Kiening KL, Kloss M, Kupsch A, et al. Thirty days complication rate following surgery performed for deep-brain-stimulation. Mov Disord. 2007;22(10):1486–9.

    PubMed  Google Scholar 

  67. Schupbach WM, Agid Y. Psychosocial adjustment after deep brain stimulation in Parkinson’s disease. Nat Clin Pract Neurol. 2008;4(2):58–9.

    PubMed  Google Scholar 

  68. Voon V, Krack P, Lang AE, Lozano AM, Dujardin K, Schupbach M, et al. A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson’s disease. Brain. 2008;131(Pt 10):2720–8.

    PubMed  Google Scholar 

  69. Hariz MI. Surgical probings into the basal ganglia: hemorrhage and hardware-related risks, and costs of microelectrode recording. Mov Disord. 2011;26(8):1375–7.

    PubMed  Google Scholar 

  70. Okun MS, Gallo BV, Mandybur G, Jagid J, Foote KD, Revilla FJ, et al. Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomised controlled trial. Lancet Neurol. 2012;11(2):140–9.

    PubMed  Google Scholar 

  71. Vergani F, Landi A, Pirillo D, Cilia R, Antonini A, Sganzerla EP. Surgical, medical, and hardware adverse events in a series of 141 patients undergoing subthalamic deep brain stimulation for Parkinson disease. World Neurosurg. 2010;73(4):338–44.

    PubMed  Google Scholar 

  72. Esselink RA, de Bie RM, de Haan RJ, Steur EN, Beute GN, Portman AT, et al. Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in Parkinson’s disease: one year follow-up of a randomised observer-blind multi centre trial. Acta Neurochir (Wien). 2006;148(12):1247–55 (discussion 1255).

    Google Scholar 

  73. Vitek JL, Bakay RA, Freeman A, Evatt M, Green J, McDonald W, et al. Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol. 2003;53(5):558–69.

    PubMed  Google Scholar 

  74. de Bie RM, Schuurman PR, de Haan PS, Bosch DA, Speelman JD. Unilateral pallidotomy in advanced Parkinson’s disease: a retrospective study of 26 patients. Mov Disord. 1999;14(6):951–7.

    PubMed  Google Scholar 

  75. Parkinson Study Group CALM Cohort Investigators. Long-term effect of initiating pramipexole vs levodopa in early Parkinson disease. Arch Neurol. 2009;66(5):563–70.

    Google Scholar 

  76. Nyholm D, Klangemo K, Johansson A. Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson’s disease. Eur J Neurol. 2012;19(8):1079–85.

    PubMed  CAS  Google Scholar 

  77. Wolf E, Seppi K, Katzenschlager R, Hochschorner G, Ransmayr G, Schwingenschuh P, et al. Long-term antidyskinetic efficacy of amantadine in Parkinson’s disease. Mov Disord. 2010;25(10):1357–63.

    PubMed  Google Scholar 

  78. Poewe W, Mahlknecht P, Jankovic J. Emerging therapies for Parkinson’s disease. Curr Opin Neurol. 2012;25(4):448–59.

    PubMed  CAS  Google Scholar 

  79. Durif F, Debilly B, Galitzky M, Morand D, Viallet F, Borg M, et al. Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study. Neurology. 2004;62(3):381–8.

    PubMed  CAS  Google Scholar 

  80. Abbott RD, Petrovitch H, White LR, Masaki KH, Tanner CM, Curb JD, et al. Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology. 2001;57(3):456–62.

    PubMed  CAS  Google Scholar 

  81. Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Marti MJ, Valldeoriola F, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006;5(7):572–7.

    PubMed  Google Scholar 

  82. Siderowf A, Stern MB. Premotor Parkinson’s disease: clinical features, detection, and prospects for treatment. Ann Neurol. 2008;64(Suppl 2):S139–47.

    PubMed  Google Scholar 

  83. Tolosa E, Poewe W. Premotor Parkinson disease. Neurology. 2009;72(7 Suppl):S1.

    PubMed  Google Scholar 

  84. Tolosa E, Gaig C, Santamaria J, Compta Y. Diagnosis and the premotor phase of Parkinson disease. Neurology. 2009;72(7 Suppl):S12–20.

    PubMed  Google Scholar 

  85. Gonera EG, van’t Hof M, Berger HJ, van Weel C, Horstink MW. Symptoms and duration of the prodromal phase in Parkinson’s disease. Mov Disord. 1997;12(6):871–6.

    PubMed  CAS  Google Scholar 

  86. Hely MA, Morris JG, Reid WG, Trafficante R. Sydney Multicenter Study of Parkinson’s disease: non-l-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20(2):190–9.

    PubMed  Google Scholar 

  87. Tandberg E, Larsen JP, Aarsland D, Cummings JL. The occurrence of depression in Parkinson’s disease. A community-based study. Arch Neurol. 1996;53(2):175–9.

    PubMed  CAS  Google Scholar 

  88. Zesiewicz TA, Gold M, Chari G, Hauser RA. Current issues in depression in Parkinson’s disease. Am J Geriatr Psychiatry. 1999;7(2):110–8.

    PubMed  CAS  Google Scholar 

  89. Witjas T, Kaphan E, Azulay JP, Blin O, Ceccaldi M, Pouget J, et al. Nonmotor fluctuations in Parkinson’s disease: frequent and disabling. Neurology. 2002;59(3):408–13.

    PubMed  Google Scholar 

  90. Barone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, et al. Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(6):573–80.

    PubMed  CAS  Google Scholar 

  91. Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, et al. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology. 2009;72(10):886–92.

    PubMed  CAS  Google Scholar 

  92. Richard IH, McDermott MP, Kurlan R, Lyness JM, Como PG, Pearson N, et al. A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology. 2012;78(16):1229–36.

    PubMed  CAS  Google Scholar 

  93. Devos D, Dujardin K, Poirot I, Moreau C, Cottencin O, Thomas P, et al. Comparison of desipramine and citalopram treatments for depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled study. Mov Disord. 2008;23(6):850–7.

    PubMed  Google Scholar 

  94. Sockeel P, Dujardin K, Devos D, Deneve C, Destee A, Defebvre L. The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2006;77(5):579–84.

    PubMed  CAS  Google Scholar 

  95. Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R, Robinson RG. Reliability, validity, and clinical correlates of apathy in Parkinson’s disease. J Neuropsychiatry Clin Neurosci. 1992;4(2):134–9.

    PubMed  CAS  Google Scholar 

  96. Chatterjee A, Fahn S. Methylphenidate treats apathy in Parkinson’s disease. J Neuropsychiatry Clin Neurosci. 2002;14(4):461–2.

    PubMed  Google Scholar 

  97. Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B. Motivation, reward, and Parkinson’s disease: influence of dopatherapy. Neuropsychologia. 2002;40(13):2257–67.

    PubMed  CAS  Google Scholar 

  98. Starkstein SE. Apathy in Parkinson’s disease: diagnostic and etiological dilemmas. Mov Disord. 2012;27(2):174–8.

    PubMed  Google Scholar 

  99. Leentjens AF, Dujardin K, Marsh L, Richard IH, Starkstein SE, Martinez-Martin P. Anxiety rating scales in Parkinson’s disease: a validation study of the Hamilton anxiety rating scale, the Beck anxiety inventory, and the hospital anxiety and depression scale. Mov Disord. 2011;26(3):407–15.

    PubMed  Google Scholar 

  100. Nuti A, Ceravolo R, Piccinni A, Dell’Agnello G, Bellini G, Gambaccini G, et al. Psychiatric comorbidity in a population of Parkinson’s disease patients. Eur J Neurol. 2004;11(5):315–20.

    PubMed  CAS  Google Scholar 

  101. Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE. Symptomatology and markers of anxiety disorders in Parkinson’s disease: a cross-sectional study. Mov Disord. 2011;26(3):484–92.

    PubMed  Google Scholar 

  102. Poewe W. Psychosis in Parkinson’s disease. Mov Disord. 2003;18(Suppl 6):S80–7.

    PubMed  Google Scholar 

  103. Fenelon G, Mahieux F, Huon R, Ziegler M. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain. 2000;123(Pt 4):733–45.

    PubMed  Google Scholar 

  104. Poewe W, Seppi K. Treatment options for depression and psychosis in Parkinson’s disease. J Neurol. 2001;248 Suppl 3:III12–21.

    Google Scholar 

  105. Borek LL, Chou KL, Friedman JH. Management of the behavioral aspects of Parkinson’s disease. Expert Rev Neurother. 2007;7(6):711–25.

    PubMed  Google Scholar 

  106. Factor SA, Friedman JH, Lannon MC, Oakes D, Bourgeois K. Clozapine for the treatment of drug-induced psychosis in Parkinson’s disease: results of the 12 week open label extension in the PSYCLOPS trial. Mov Disord. 2001;16(1):135–9.

    PubMed  CAS  Google Scholar 

  107. Merims D, Balas M, Peretz C, Shabtai H, Giladi N. Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson’s disease psychosis. Clin Neuropharmacol. 2006;29(6):331–7.

    PubMed  CAS  Google Scholar 

  108. Atkin K, Kendall F, Gould D, Freeman H, Liberman J, O’Sullivan D. Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland. Br J Psychiatry. 1996;169(4):483–8.

    PubMed  CAS  Google Scholar 

  109. Honigfeld G, Arellano F, Sethi J, Bianchini A, Schein J. Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry. J Clin Psychiatry. 1998;59(Suppl 3):3–7.

    PubMed  Google Scholar 

  110. Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993;329(3):162–7.

    PubMed  CAS  Google Scholar 

  111. Goetz CG, Stebbins GT. Risk factors for nursing home placement in advanced Parkinson’s disease. Neurology. 1993;43(11):2227–9.

    PubMed  CAS  Google Scholar 

  112. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837–44.

    PubMed  Google Scholar 

  113. Forsaa EB, Larsen JP, Wentzel-Larsen T, Alves G. What predicts mortality in Parkinson disease? A prospective population-based long-term study. Neurology. 2010;75(14):1270–6.

    PubMed  CAS  Google Scholar 

  114. Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22(12):1689–707 (quiz 1837).

    Google Scholar 

  115. Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord. 2005;20(10):1255–63.

    PubMed  Google Scholar 

  116. Emre M. Treatment of dementia associated with Parkinson’s disease. Parkinsonism Relat Disord. 2007;13(Suppl 3):S457–61.

    PubMed  Google Scholar 

  117. Reid WG, Hely MA, Morris JG, Loy C, Halliday GM. Dementia in Parkinson’s disease: a 20-year neuropsychological study (Sydney Multicentre Study). J Neurol Neurosurg Psychiatry. 2011;82(9):1033–7.

    PubMed  CAS  Google Scholar 

  118. Leroi I, Overshott R, Byrne EJ, Daniel E, Burns A. Randomized controlled trial of memantine in dementia associated with Parkinson’s disease. Mov Disord. 2009;24(8):1217–21.

    PubMed  Google Scholar 

  119. Aarsland D, Ballard C, Walker Z, Bostrom F, Alves G, Kossakowski K, et al. Memantine in patients with Parkinson’s disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 2009;8(7):613–8.

    PubMed  CAS  Google Scholar 

  120. Emre M, Tsolaki M, Bonuccelli U, Destee A, Tolosa E, Kutzelnigg A, et al. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(10):969–77.

    PubMed  CAS  Google Scholar 

  121. Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351(24):2509–18.

    PubMed  CAS  Google Scholar 

  122. Lahrmann H, Cortelli P, Hilz M, Mathias CJ, Struhal W, Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol. 2006;13(9):930–6.

    PubMed  CAS  Google Scholar 

  123. Bonuccelli U, Lucetti C, Del Dotto P, Ceravolo R, Gambaccini G, Bernardini S, et al. Orthostatic hypotension in de novo Parkinson disease. Arch Neurol. 2003;60(10):1400–4.

    PubMed  Google Scholar 

  124. Magalhaes M, Wenning GK, Daniel SE, Quinn NP. Autonomic dysfunction in pathologically confirmed multiple system atrophy and idiopathic Parkinson’s disease: a retrospective comparison. Acta Neurol Scand. 1995;91(2):98–102.

    PubMed  CAS  Google Scholar 

  125. Wenning GK, Scherfler C, Granata R, Bosch S, Verny M, Chaudhuri KR, et al. Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study. J Neurol Neurosurg Psychiatry. 1999;67(5):620–3.

    PubMed  CAS  Google Scholar 

  126. Denq JC, Opfer-Gehrking TL, Giuliani M, Felten J, Convertino VA, Low PA. Efficacy of compression of different capacitance beds in the amelioration of orthostatic hypotension. Clin Auton Res. 1997;7(6):321–6.

    PubMed  CAS  Google Scholar 

  127. Tanaka H, Yamaguchi H, Tamai H. Treatment of orthostatic intolerance with inflatable abdominal band. Lancet. 1997;349(9046):175.

    PubMed  CAS  Google Scholar 

  128. Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension: a randomized, double-blind multicenter study. Midodrine Study Group. JAMA. 1997;277(13):1046–51.

    PubMed  CAS  Google Scholar 

  129. Jankovic J, Gilden JL, Hiner BC, Kaufmann H, Brown DC, Coghlan CH, et al. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med. 1993;95(1):38–48.

    PubMed  CAS  Google Scholar 

  130. Suchowersky O, Furtado S, Rohs G. Beneficial effect of intranasal desmopressin for nocturnal polyuria in Parkinson’s disease. Mov Disord. 1995;10(3):337–40.

    PubMed  CAS  Google Scholar 

  131. Winge K, Fowler CJ. Bladder dysfunction in Parkinsonism: mechanisms, prevalence, symptoms, and management. Mov Disord. 2006;21(6):737–45.

    PubMed  Google Scholar 

  132. Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, et al. Review of the therapeutic management of Parkinson’s disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated) Parkinson’s disease. Eur J Neurol. 2006;13(11):1186–202.

    PubMed  CAS  Google Scholar 

  133. Conte A, Giannantoni A, Proietti S, Giovannozzi S, Fabbrini G, Rossi A, et al. Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity. Eur J Neurol. 2012;19(5):725–32.

    PubMed  CAS  Google Scholar 

  134. Hussain IF, Brady CM, Swinn MJ, Mathias CJ, Fowler CJ. Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson’s disease or multiple system atrophy with observations on orthostatic hypotension. J Neurol Neurosurg Psychiatry. 2001;71(3):371–4.

    PubMed  CAS  Google Scholar 

  135. Safarinejad MR, Taghva A, Shekarchi B, Safarinejad S. Safety and efficacy of sildenafil citrate in the treatment of Parkinson-emergent erectile dysfunction: a double-blind, placebo-controlled, randomized study. Int J Impot Res. 2010;22(5):325–35.

    PubMed  CAS  Google Scholar 

  136. Dula E, Bukofzer S, Perdok R, George M. Double-blind, crossover comparison of 3 mg apomorphine SL with placebo and with 4 mg apomorphine SL in male erectile dysfunction. Eur Urol. 2001;39(5):558–3 (discussion 64).

    Google Scholar 

  137. Friedman JH, Chou KL. Sleep and fatigue in Parkinson’s disease. Parkinsonism Relat Disord. 2004;10(Suppl 1):S27–35.

    PubMed  Google Scholar 

  138. Comella CL, Nardine TM, Diederich NJ, Stebbins GT. Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson’s disease. Neurology. 1998;51(2):526–9.

    PubMed  CAS  Google Scholar 

  139. Stiasny-Kolster K, Magerl W, Oertel WH, Moller JC, Treede RD. Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome. Brain. 2004;127(Pt 4):773–82.

    PubMed  CAS  Google Scholar 

  140. Bjørnarå KA, Dietrichs E, Toft M. REM sleep behavior disorder in Parkinson’s disease—is there a gender difference? Parkinsonism Relat Disord. 2013;19(1):120–2

    Google Scholar 

  141. Ozekmekci S, Apaydin H, Kilic E. Clinical features of 35 patients with Parkinson’s disease displaying REM behavior disorder. Clin Neurol Neurosurg. 2005;107(4):306–9.

    PubMed  Google Scholar 

  142. Schenck CH, Mahowald MW. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Med. 1996;100(3):333–7.

    PubMed  CAS  Google Scholar 

  143. Schenck CH, Bundlie SR, Patterson AL, Mahowald MW. Rapid eye movement sleep behavior disorder: a treatable parasomnia affecting older adults. JAMA. 1987;257(13):1786–9.

    PubMed  CAS  Google Scholar 

  144. Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281–4.

    PubMed  Google Scholar 

  145. Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord. 1999;14(3):507–11.

    PubMed  CAS  Google Scholar 

  146. Ondo WG, Vuong KD, Jankovic J. Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol. 2002;59(3):421–4.

    PubMed  Google Scholar 

  147. Sophie M, Ford B. Management of pain in Parkinson’s disease. CNS Drugs. 2012;26(11):937–48.

    PubMed  CAS  Google Scholar 

  148. Bonnet AM, Jutras MF, Czernecki V, Corvol JC, Vidailhet M. Nonmotor symptoms in Parkinson’s disease in 2012: relevant clinical aspects. Parkinsons Dis. 2012;2012:198316.

    PubMed  Google Scholar 

  149. Ford B. Parkinson disease: pain in Parkinson disease: the hidden epidemic. Nat Rev Neurol. 2009;5(5):242–3.

    PubMed  Google Scholar 

  150. Beiske AG, Loge JH, Ronningen A, Svensson E. Pain in Parkinson’s disease: prevalence and characteristics. Pain. 2009;141(1–2):173–7.

    PubMed  CAS  Google Scholar 

  151. Ha AD, Jankovic J. Pain in Parkinson’s disease. Mov Disord. 2012;27(4):485–91.

    PubMed  Google Scholar 

  152. Van Blercom N, Lasa A, Verger K, Masramon X, Sastre VM, Linazasoro G. Effects of gabapentin on the motor response to levodopa: a double-blind, placebo-controlled, crossover study in patients with complicated Parkinson disease. Clin Neuropharmacol. 2004;27(3):124–8.

    PubMed  Google Scholar 

  153. Loher TJ, Burgunder JM, Weber S, Sommerhalder R, Krauss JK. Effect of chronic pallidal deep brain stimulation on off period dystonia and sensory symptoms in advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2002;73(4):395–9.

    PubMed  CAS  Google Scholar 

  154. Maruo T, Saitoh Y, Hosomi K, Kishima H, Shimokawa T, Hirata M, et al. Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson’s disease. Pain. 2011;152(4):860–5.

    PubMed  Google Scholar 

  155. Djaldetti R, Yust-Katz S, Kolianov V, Melamed E, Dabby R. The effect of duloxetine on primary pain symptoms in Parkinson disease. Clin Neuropharmacol. 2007;30(4):201–5.

    PubMed  CAS  Google Scholar 

  156. Olanow CW, Agid Y, Mizuno Y, Albanese A, Bonuccelli U, Damier P, et al. Levodopa in the treatment of Parkinson’s disease: current controversies. Mov Disord. 2004;19(9):997–1005.

    PubMed  Google Scholar 

Download references

Acknowledgments

No funding was received to prepare this article. Werner Poewe has received consultancy and lecture fees from Abbott, AstraZeneca, Teva, Novartis, GlaxoSmithKline, Boehringer-Ingelheim, UCB, Orion Pharma, Merck Serono and Merz Pharmaceuticals in relation to clinical drug development programmes for Parkinson’s disease. Fabienne Sprenger has no conflicts of interest that are directly relevant to the content of this article.

Author information

Authors and Affiliations

  1. Department of Neurology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria

    Fabienne Sprenger & Werner Poewe

Authors
  1. Fabienne Sprenger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Werner Poewe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabienne Sprenger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sprenger, F., Poewe, W. Management of Motor and Non-Motor Symptoms in Parkinson’s Disease. CNS Drugs 27, 259–272 (2013). https://doi.org/10.1007/s40263-013-0053-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-013-0053-2

Keywords

Search

Navigation