Parkinsonian Drugs: Guidelines for Japan

  • Yoshikuni MizunoEmail author
Living reference work entry


Drugs for Parkinson’s disease (PD) permitted by the Department of Health, Labor and Welfare in Japan now (as of October, 2017) includes l-dopa, l-dopa/DCI (dopa decarboxylase inhibitor), l-dopa/DCI for intra-jejunal injection, dopamine agonists (bromocriptine, pergolide, cabergoline, pramipexole, ropinirole, rotigotine, and apomorphine), selegiline, entacapone, zonisamide, istradefylline, amantadine, anti-cholinergics (trihexyphenidyl and others), and droxidopa. The first guideline for PD was published in 2003. It was revised in 2011 and 2018. In the edition, newer drugs such as rotigotine, apomorphine, and istradefylline have been added. As the third version was not published when this version was completed, the second edition was adopted. The Guideline Committee reviewed vast numbers of articles since 1983 until September, 2008. In the second guideline, clinical efficacy and safety of each anti-PD drug was described. The evidence level adopted was that of Minds treatment guidelines as follows: I; conclusions obtained by the systematic review or the meta-analysis of the randomized control trials (RCT), and II, III, IV, V, VI with decreasing confidence. In the second part of the revised guideline, 42 clinical questions such as “When anti-PD drugs should be started for PD?” were raised and the recommendations of the Guideline Committee were added according to the Minds degree of probability for each question as follows: A; strong scientific evidences are present and it is strongly to follow their recommendations, B, C, D with decreasing confidence. The Guideline Committee made the conclusion as efficacious and safe or probably safe in all of the anti-PD drugs listed above. But for the ergot dopamine agonists, the Committee was the opinion that they should not be used as the first-line treatment.


  1. Alvarez L, Macias R, Guridi J, Lopez G, Alvarez E, Maragoto C, Teijeiro J, Torres A, Pavon N, Rodriguez-Oroz MC, Ochoa L, Hetherington H, Juncos J, DeLong MR, Obeso JA. Dorsal subthalamotomy for Parkinson’s disease. Mov Disord. 2001;16(1):72–8.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Antonini A, Tesei S, Zecchinelli A, Barone P, De Gaspari D, Canesi M, Sacilotto G, Meucci N, Mariani C, Pezzoli G. Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson’s disease and depression: effect on quality of life. Mov Disord. 2006;21(8): 1119–22.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Antonini A, Yegin A, Preda C, Bergmann L, Poewe W, GLORIA Study Investigators and Coordinators. Global long-term study on motor and non-motor symptoms and safety of levodopa-carbidopa intestinal gel in routine care of advanced Parkinson’s disease patients; 12-month interim outcomes. Parkinsonism Relat Disord. 2015;21(3):231–5. Epub 2014 Dec 19.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bédard MA, Pillon B, Dubois B, Duchesne N, Masson H, Agid Y. Acute and long-term administration of anticholinergics in Parkinson’s disease: specific effects on the subcortico-frontal syndrome. Brain Cogn. 1999;40(2):289–313.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Bracco F, Battaglia A, Chouza C, Dupont E, Gershanik O, Marti Masso JF, Montastruc JL, PKDS009 Study Group. The long-acting dopamine receptor agonist cabergoline in early Parkinson’s disease: final results of a 5-year, double-blind, levodopa-controlled study. CNS Drugs. 2004;18(11):733–46.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Brefel-Courbon C, Payoux P, Thalamas C, Ory F, Quelven I, Chollet F, Montastruc JL, Rascol O. Effect of levodopa on pain threshold in Parkinson’s disease: a clinical and positron emission tomography study. Mov Disord. 2005;20(12):1557–63.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Brocks DR. Anticholinergic drugs used in Parkinson’s disease: an overlooked class of drugs from a pharmacokinetic perspective. J Pharm Pharmaceut Sci. 1999;2(2):39–46.Google Scholar
  8. Brooks DJ, Sagar H, UK-Irish Entacapone Study Group. Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson’s disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry. 2003;74(8):1071–9.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, Van Brocklin HF, Wright JF, Bankiewicz KS, Aminoff MJ. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology. 2009;73(20):1662–9. Epub 2009 Oct 14.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Comella CL, Stebbins GT, Brown-Toms N, Goetz CG. Physical therapy and Parkinson’s disease: a controlled clinical trial. Neurology. 1994;44(3 Pt 1):376–8.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Constantinescu R, Romer M, McDermott MP, Kamp C, Kieburtz K, CALM-PD Investigators of the Parkinson Study Group. Impact of pramipexole on the onset of levodopa-related dyskinesias. Mov Disord. 2007;22(9):1317–9.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Corvol JC, Anzouan-Kacou JB, Fauveau E, Bonnet AM, Lebrun-Vignes B, Girault C, Agid Y, Lechat P, Isnard R, Lacomblez L. Heart valve regurgitation, pergolide use, and Parkinson disease: an observational study and meta-analysis. Arch Neurol. 2007;64(12):1721–6.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Dallos V, Heathfield K, Stone P, Allen FAD. Use of amantadine in Parkinson’s disease. Results of a double-blind trial. Br Med J. 1970;4:24–6.PubMedPubMedCentralCrossRefGoogle Scholar
  14. de Lau LM, Schipper CM, Hofman A, Koudstaal PJ, Breteler MM. Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study. Arch Neurol. 2005;62(8):1265–9.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Deep-Brain Stimulation for Parkinson’s Disease Study Group, Obeso JA, Olanow CW, Rodriguez-Oroz MC, Krack P, Kumar R, Lang AE. 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(13): 956–63.CrossRefGoogle Scholar
  16. Deleu D, Hanssens Y, Northway MG. Subcutaneous apomorphine: an evidence-based review of its use in Parkinson’s disease. Drugs Aging. 2004;21(11):687–709.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K, Daniels C, Deutschländer A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J, German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355(9):896–908.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Doshay LJ, Constable K, Zier A. Five year follow-up of treatment with trihexyphenidyl (artane); outcome in four hundred eleven cases of paralysis agitans. J Am Med Assoc. 1954;154(16):1334–6.PubMedCrossRefPubMedCentralGoogle Scholar
  19. Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, Durif F, Kulisevsky J, van Laar T, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351(24): 2509–18.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, Lew MF, Odin P, Steiger M, Yakupov EZ, Chouinard S, Suchowersky O, Dubow J, Hall CM, Chatamra K, Robieson WZ, Benesh JA, Espay AJ. Levodopa-carbidopa intestinal gel in advanced Parkinson’s disease: final 12-month, open-label results. Mov Disord. 2015;30(4):500–9. Epub 2014.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 2001;344(10):710–9.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Fukui T, Yamaguchi N. Minds handbook for clinical practice guideline development 2007. Tokyo: Igakushoin; 2007. (Japanese) (English version is available by internet).Google Scholar
  23. Goetz CG, Poewe W, Rascol O, Sampaio C. Evidence-based medical review update: pharmacological and surgical treatments of Parkinson’s disease: 2001. Mov Disord. 2005;20(5):523–39.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL. The effectiveness of exercise interventions for people with Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2008;23(5):631–40. Scholar
  25. Grosset D, Taurah L, Burn DJ, MacMahon D, Forbes A, Turner K, Bowron A, Walker R, Findley L, Foster O, Patel K, Clough C, Castleton B, Smith S, Carey G, Murphy T, Hill J, Brechany U, McGee P, Reading S, Brand G, Kelly L, Breen K, Ford S, Baker M, Williams A, Hearne J, Qizilbash N, Chaudhuri KR. A multicentre longitudinal observational study of changes in self-reported health status in people with Parkinson’s disease left untreated at diagnosis. J Neurol Neurosurg Psychiatry. 2007;78(5):465–9. Epub 2006 Nov 10.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Hamada M, Ugawa Y, Tsuji S, Effectiveness of rTMS on Parkinson’s Disease Study Group, Japan. High-frequency rTMS over the supplementary motor area for treatment of Parkinson’s disease. Mov Disord. 2008;23(11):1524–31. Scholar
  27. Hattori N, Nomoto M, 6500-004 Study Group. Sustained efficacy of apomorphine in Japanese patients with advanced Parkinson’s disease. Parkinsonism Relat Disord. 2014;20(8):819–23. Epub 2014 Apr 18.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Hauser RA, Hubble JP, Truong DD, Istradefylline US-001 Study Group. Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology. 2003;61(3):297–303.PubMedCrossRefPubMedCentralGoogle Scholar
  29. Hauser RA, Rascol O, Korczyn AD, Jon Stoessl A, Watts RL, Poewe W, De Deyn PP, Lang AE. Ten-year follow-up of Parkinson’s disease patients randomized to initial therapy with ropinirole or levodopa. Mov Disord. 2007;22(16):2409–17.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Hauser RA, Panisset M, Abbruzzese G, Mancione L, Dronamraju N, Kakarieka A, FIRST-STEP Study Group. Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson’s disease. Mov Disord. 2009;24(4):541–50. Scholar
  31. Hauser RA, Isaacson S, Lisk JP, Hewitt LA, Rowse G. Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson’s disease (nOH306B). Mov Disord. 2015;30(5):646–54. Epub 2014 Dec 9.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hely MA, Morris JG, Traficante R, Reid WG, O’Sullivan DJ, Williamson PM. The Sydney multicentre study of Parkinson’s disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry. 1999;67(3):300–7.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Hirayama K, Uono M, Nakanishi T, Kato N, Nagao Y. Therapeutic effects of L-dopa and trihexyphenidyl in Parkinson’s disease – an examination by a double blind method. Shinkei Kenkyu No Shimpo. 1971;15(1):267–85. (Japanese).PubMedPubMedCentralGoogle Scholar
  34. Holloway RG, Shoulson I, Fahn S, Kieburtz K, Lang A, Marek K, McDermott M, Seibyl J, Weiner W, Musch B, Kamp C, Welsh M, Shinaman A, Pahwa R, Barclay L, Hubble J, LeWitt P, Miyasaki J, Suchowersky O, Stacy M, Russell DS, Ford B, Hammerstad J, Riley D, Standaert D, Wooten F, Factor S, Jankovic J, Atassi F, Kurlan R, Panisset M, Rajput A, Rodnitzky R, Shults C, Petsinger G, Waters C, Pfeiffer R, Biglan K, Borchert L, Montgomery A, Sutherland L, Weeks C, DeAngelis M, Sime E, Wood S, Pantella C, Harrigan M, Fussell B, Dillon S, Alexander-Brown B, Rainey P, Tennis M, Rost-Ruffner E, Brown D, Evans S, Berry D, Hall J, Shirley T, Dobson J, Fontaine D, Pfeiffer B, Brocht A, Bennett S, Daigneault S, Hodgeman K, O’Connell C, Ross T, Richard K, Watts A, Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol. 2004;61(7):1044–53.PubMedPubMedCentralGoogle Scholar
  35. Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, Gray R, Wheatley K. Monoamine oxidase type B inhibitors in early Parkinson’s disease: meta-analysis of 17 randomised trials involving 3525 patients. BMJ. 2004;329(7466):593. Epub 2004 Aug 13.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet. 2007;369(9579):2097–105.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Karlsen KH, Larsen JP, Tandberg E, Maeland JG. Influence of clinical and demographic variables on quality of life in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1999;66(4):431–5.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Katzenschlager R, Head J, Schrag A, Ben-Shlomo Y, Evans A, Lees AJ, Parkinson’s Disease Research Group of the United Kingdom. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology. 2008;71(7):474–80. Epub 2008 Jun.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, Mauney J, Feirtag M, Mathias CJ, NOH301 Investigators. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328–35. Epub 2014 Jun 18.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Krause M, Fogel W, Heck A, Hacke W, Bonsanto M, Trenkwalder C, Tronnier V. Deep brain stimulation for the treatment of Parkinson’s disease: subthalamic nucleus versus globus pallidus internus. J Neurol Neurosurg Psychiatry. 2001;70(4):464–70.PubMedPubMedCentralCrossRefGoogle Scholar
  41. LeWitt PA, Lyons KE, Pahwa R, SP 650 Study Group. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology. 2007;68(16):1262–7.PubMedCrossRefPubMedCentralGoogle Scholar
  42. LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM, 6002-US-005 Study Group. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol. 2008;63(3):295–302.PubMedPubMedCentralCrossRefGoogle Scholar
  43. LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Thomas K, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Van Meter L, Sapan CV, During MJ, Kaplitt MG, Feigin A. AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol. 2011;10(4):309–19. Scholar
  44. Lou JS, Kearns G, Benice T, Oken B, Sexton G, Nutt J. Levodopa improves physical fatigue in Parkinson’s disease: a double-blind, placebo-controlled, crossover study. Mov Disord. 2003;18(10):1108–14.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Marks WJ Jr, Ostrem JL, Verhagen L, Starr PA, Larson PS, Bakay RA, Taylor R, Cahn-Weiner DA, Stoessl AJ, Olanow CW, Bartus RT. Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson’s disease: an open-label, phase I trial. Lancet Neurol. 2008;7(5):400–8. Epub 2008 Apr 2.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Marks WJ Jr, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, Vitek J, Stacy M, Turner D, Verhagen L, Bakay R, Watts R, Guthrie B, Jankovic J, Simpson R, Tagliati M, Alterman R, Stern M, Baltuch G, Starr PA, Larson PS, Ostrem JL, Nutt J, Kieburtz K, Kordower JH, Olanow CW. Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2010;9(12):1164–72. Epub 2010 Oct 20.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Marras C, Rochon P, Lang AE. Predicting motor decline and disability in Parkinson disease: a systematic review. Arch Neurol. 2002;59(11):1724–8.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Marras C, McDermott MP, Rochon PA, Tanner CM, Naglie G, Rudolph A, Lang AE, Parkinson Study Group. Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort. Neurology. 2005;64(1):87–93.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Buyske S, Bienfait K, Dicke A. A controlled trial of antidepressants in patients with Parkinson disease and depression. Neurology. 2009;72(10):886–92. Epub 2008 Dec 17.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Mizuno Y, Hasegawa K, Kondo T, Kuno S, Yamamoto M, Japanese Istradefylline, Stacy M, Silver D, Mendis T, Sutton J, Mori A, Chaikin P, Sussman NM. A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease. Neurology. 2008;70(23):2233–40.CrossRefGoogle Scholar
  51. Mizuno Y, Hasegawa K, Kondo T, Kuno S, Yamamoto M, Japanese Istradefylline Study Group. Clinical efficacy of istradefylline (KW-6002) in Parkinson’s disease: a randomized, controlled study. Mov Disord. 2010;25(10):1437–43. Scholar
  52. Mizuno Y, Kondo T. Japanese Istradefylline Study Group. Adenosine A2A receptor antagonist istradefylline reduces daily OFF time in Parkinson’s disease. MovDisord. 2013;28(8):1138–41.Google Scholar
  53. Mizuno Y, Hattori N, Kondo T, Nomoto M, Origasa H, Takahashi R, Yamamoto M, Yanagisawa N. A randomized double-blind placebo-controlled phase III trial of selegiline monotherapy for early Parkinson’s disease. Clin Neuropharmacol. 2017. (in press).Google Scholar
  54. Muramatsu S, Fujimoto K, Kato S, Mizukami H, Asari S, Ikeguchi K, Kawakami T, Urabe M, Kume A, Sato T, Watanabe E, Ozawa K, Nakano I. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Mol Ther. 2010;18(9):1731–5. Epub 2010 Jul 6.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Murata M, Hasegawa K, Kanazawa I, Japan Zonisamide on PD Study Group. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007;68(1): 45–50.PubMedCrossRefPubMedCentralGoogle Scholar
  56. Murata M, Hasegawa K, Kanazawa I, Fukasaka J, Kochi K, Shimazu R, Japan Zonisamide on PD Study Group. Zonisamide improves wearing-off in Parkinson’s disease: a randomized, double-blind study. Mov Disord. 2015;30(10):1343–50. Epub 2015 Jun 12.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Narabayashi H, Nakanishi T, Yoshida M, Yanagisawa N, Mizuno Y, Kanazawa I, Kondo T. Therapeutic effect of L-dopa in Parkinson’s disease: double blind, comparative study against placebo as control in patients with the long-term levodopa therapy. Clin Eval. 1997;15:423–57. (Japanese with English summary).Google Scholar
  58. Nomoto M, Kubo S, Nagai M, Yamada T, Tamaoka A, Tsuboi Y, Hattori N, PD Study Group. A randomized controlled trial of subcutaneous Apomorphine for Parkinson disease: a repeat dose and pharmacokinetic study. Clin Neuropharmacol. 2015;38(6):241–7. Scholar
  59. Oertel WH, Wolters E, Sampaio C, Gimenez-Roldan S, Bergamasco B, Dujardin M, Grosset DG, Arnold G, Leenders KL, Hundemer HP, Lledó A, Wood A, Frewer P, Schwarz J. Pergolide versus levodopa monotherapy in early Parkinson’s disease patients: the PELMOPET study. Mov Disord. 2006;21(3):343–53.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Olanow CW, Rascol O, Hauser R, Feigin PD, Jankovic J, Lang A, Langston W, Melamed E, Poewe W, Stocchi F, Tolosa E, ADAGIO Study Investigators. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med. 2009;361(13):1268–78.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanagunas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A, LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2014;13(2):141–9. Epub 2013 Dec 20.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain. 2000;123(Pt 2):331–9.PubMedCrossRefPubMedCentralGoogle Scholar
  63. Ondo WG, Tintner R, Voung KD, Lai D, Ringholz G. Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson’s disease. Mov Disord. 2005;20(8):958–63.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, Hallett M, Miyasaki J, Stevens J, Weiner WJ, Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the quality standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):983–95.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Pahwa R, Koller WC, Trosch RM, Sherry JH, APO303 Study Investigators. Subcutaneous apomorphine in patients with advanced Parkinson’s disease: a dose-escalation study with randomized, double-blind, placebo-controlled crossover evaluation of a single dose. J Neurol Sci. 2007;258(1–2):137–43. Epub 2007 Apr 27.PubMedCrossRefPubMedCentralGoogle Scholar
  66. Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Parkinson Study Group. Ann Neurol. 1997;42(5):747–55.CrossRefGoogle Scholar
  67. Parkinson Study Group. Mortality in DATATOP: a multicenter trial in early Parkinson’s disease. Parkinson Study Group. Ann Neurol. 1998;43(3):318–25.CrossRefGoogle Scholar
  68. Parkinson Study Group. A controlled trial of rotigotine monotherapy in early Parkinson’s disease. Arch Neurol. 2003;60(12):1721–8.CrossRefGoogle Scholar
  69. Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol. 2004a;61(4):561–6.CrossRefGoogle Scholar
  70. Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol. 2004b;61(7):1044–53.Google Scholar
  71. Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol. 2005;62(2):241–8.CrossRefGoogle Scholar
  72. Paus S, Brecht HM, Köster J, Seeger G, Klockgether T, Wüllner U. Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson’s disease. Mov Disord. 2003;18(6):659–67.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Perry EK, Kilford L, Lees AJ, Burn DJ, Perry RH. Increased Alzheimer pathology in Parkinson’s disease related to antimuscarinic drugs. Ann Neurol. 2003;54(2):235–8.PubMedCrossRefPubMedCentralGoogle Scholar
  74. Pfeiffer RF, Gutmann L, Hull KL Jr, Bottini PB, Sherry JH, APO302 Study Investigators. Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson’s disease. Parkinsonism Relat Disord. 2007;13(2):93–100. Epub 2006 Oct 18.PubMedCrossRefPubMedCentralGoogle Scholar
  75. Rabey JM, Prokhorov T, Miniovitz A, Dobronevsky E, Klein C. Effect of quetiapine in psychotic Parkinson’s disease patients: a double-blind labeled study of 3 months’ duration. Mov Disord. 2007;22(3):313–8.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  77. Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE, Abdalla M, 056 Study Group. Development of dyskinesias in a 5-year trial of ropinirole and L-dopa. Mov Disord. 2006;21(11):1844–50.PubMedCrossRefPubMedCentralGoogle Scholar
  78. Ravina B, Putt M, Siderowf A, Farrar JT, Gillespie M, Crawley A, Fernandez HH, Trieschmann MM, Reichwein S, Simuni T. Donepezil for dementia in Parkinson’s disease: a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry. 2005;76(7): 934–9.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Rektorová I, Rektor I, Bares M, Dostál V, Ehler E, Fanfrdlová Z, Fiedler J, Klajblová H, Kulist’ák P, Ressner P, Svátová J, Urbánek K, Velísková J. Pramipexole and pergolide in the treatment of depression in Parkinson’s disease: a national multicentre prospective randomized study. Eur J Neurol. 2003;10(4):399–406.PubMedCrossRefPubMedCentralGoogle Scholar
  80. Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson’s disease? J Neurol Neurosurg Psychiatry. 2000;69(3):308–12.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Schuurman PR, Bosch DA, Merkus MP, Speelman JD. Long-term follow-up of thalamic stimulation versus thalamotomy for tremor suppression. Mov Disord. 2008;23(8):1146–53. Scholar
  82. Shoulson I, Oakes D, Fahn S, Lang A, Langston JW, LeWitt P, Olanow CW, Penney JB, Tanner C, Kieburtz K, Rudolph A, Parkinson Study Group. Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson’s disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Ann Neurol. 2002;51(5):604–12.PubMedCrossRefPubMedCentralGoogle Scholar
  83. Simonis G, Fuhrmann JT, Strasser RH. Meta-analysis of heart valve abnormalities in Parkinson’s disease patients treated with dopamine agonists. Mov Disord. 2007;22(13):1936–42.PubMedCrossRefPubMedCentralGoogle Scholar
  84. Stacy M, Silver D, Mendis T, Sutton J, Mori A, Chaikin P, Sussman NM. A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease. Neurology. 2008;70(23):2233–40. Scholar
  85. Stocchi F, Rascol O, Kieburtz K, Poewe W, Jankovic J, Tolosa E, Barone P, Lang AE, Olanow CW. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol. 2010;68(1):18–27. Scholar
  86. Stowe RL, Ives NJ, Clarke C, van Hilten J, Ferreira J, Hawker RJ, Shah L, Wheatley K, Gray R. Dopamine agonist therapy in early Parkinson’s disease. Cochrane Database Syst Rev. 2008;2:CD006564. Scholar
  87. Su PC, Tseng HM, Liu HM, Yen RF, Liou HH. Subthalamotomy for advanced Parkinson disease. J Neurosurg. 2002;97(3):598–606.PubMedCrossRefPubMedCentralGoogle Scholar
  88. The Global Parkinson’s Disease Survey (GPDS) Steering Committee. Factors impacting on quality of life in Parkinson’s disease: results from an international survey. Mov Disord. 2002;17:60–7.CrossRefGoogle Scholar
  89. The Guideline Committee for the Treatment of Parkinson’s Disease. The guideline for the treatment of Parkinson’s disease. Rinshoshinkeigaku. 2002;42:428–94. (Japanese).Google Scholar
  90. The Guideline Committee for the Treatment of Parkinson’s Disease. The guideline for the treatment of Parkinson’s disease. Tokyo: Igakushoin; 2003. (Japanese).Google Scholar
  91. The Guideline Committee for the Treatment of Parkinson’s Disease. The guidelines of the treatment of Parkinson’s disease 2011. Tokyo: Igakushoin; 2011. pp. 1–198. (Japanese).Google Scholar
  92. The Guideline Committee for the Treatnent of PD. The guidlines of the treatment of PD. 2018, Tokyo, Igakushoin; 2018. pp. 1–288.Google Scholar
  93. Valálik I, Sági S, Solymosi D, Julow J. CT-guided unilateral thalamotomy with macroelectrode mapping for the treatment of Parkinson’s disease. Acta Neurochir. 2001;143(10):1019–30.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Vignatelli L, Billiard M, Clarenbach P, Garcia-Borreguero D, Kaynak D, Liesiene V, Trenkwalder C, Montagna P, EFNS Task Force. EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep. Eur J Neurol. 2006;13(10): 1049–65.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Vitek JL, Bakay RA, Freeman A, Evatt M, Green J, McDonald W, Haber M, Barnhart H, Wahlay N, Triche S, Mewes K, Chockkan V, Zhang JY, DeLong MR. Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Ann Neurol. 2003;53(5):558–69.PubMedCrossRefPubMedCentralGoogle Scholar
  96. Voon V, Hassan K, Zurowski M, de Souza M, Thomsen T, Fox S, Lang AE, Miyasaki J. Prevalence of repetitive and reward-seeking behaviors in Parkinson disease. Neurology. 2006;67(7): 1254–7. Epub 2006 Sep 6.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 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.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Juntendo University School of MedicineTokyoJapan

Section editors and affiliations

  • Toshiharu Nagatsu
    • 1
    • 2
  • Akira Nakashima
    • 3
  1. 1.Fujita Health University School of MedicineToyoakeJapan
  2. 2.Institute of Environmental MedicineNagoya UniversityNagoyaJapan
  3. 3.Department of Physiological ChemistryFujita Health University School of MedicineToyoake, AichiJapan

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