Abstract
There are many guidelines available concerning the treatment of Parkinson’s disease. Most of these advocate treating young-onset patients with a dopamine agonist and older patients with levodopa. The rationale behind this recommendation has its origins in the side effects associated with each of these drug classes: whilst levodopa leads to dyskinesia, which may not be relevant for patients with a limited life-expectancy, dopamine agonists have a much longer plasma half life which probably leads to more continuous dopamine receptor stimulation and thus decreases the occurrence and severity of dyskinesia. However, the side effects associated with the use of dopamine agonists, such as sleepiness, orthostatic problems, hallucinations and impulse control disorders are a drawback. In this overview, the hypothesis will be put forward that perhaps such a strict distinction is no longer needed. A new idea may be the early combination of levodopa with a dopamine agonist which would provide good clinical efficacy and, because of the relatively low doses involved, would reduce the side effects associated with both substances. MAO-B inhibitors may be a good option for early treatment and especially for patients who experience first motor fluctuations. Similarly, and particularly if a wearing-off symptom is present, COMT inhibitors smoothen and prolong the action of levodopa. More invasive escalation therapy comes into play when patients reach the advanced stages with problems of insufficient motor control, such as bradykinesia, rigidity and resting tremor, combined with on-time dyskinesia. The use of all oral and invasive treatment has to be individualized to gain a good motor and non-motor control and especially a good quality of life.
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Abbott RD, Petrovitch J, Withe LR, Masaki KH, Tanner CM, Curb JD, Grandinetti A, Blanchette PL, Popper JS, Ross GW (2001) Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 57:456–462
Bonuccelli U, Ceravolo R, Salvetti S, D’Avino C, Del Dotto P, Rossi G, Murri L (1997) Clozapine in Parkinson’s disease tremor. Effects of acute and chronic administration. Neurology 49:1587–1590
Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt M, Chirilineau D, Stocchi F, Lucini V, Giuliani R, Forrest E, Rice P, Anand R, Study 016 Investigators (2014a) Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord 29:229–237
Braak H, Del Tredici K, Bratzke H, Hamm-Clement J, Sandmann-keil D, Rueb U (2002) Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). J Neurol 249 Suppl 3:III/1–III/5
Caccia C, Maj R, Calabresi M, Maestroni S, Faravelli L, Curatolo L, Salvati P, Fariello RG (2006) Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology 67(7 Suppl 2):S18–S23
Cerosimo MG, Raina GB, Pecci C, Pellene A, Calandra CR, Gutiérrez C, Micheli FE, Benarroch EE (2013) Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol 260:1332–1338
Chaudhuri KR, Odin P (2010) The challenge of non-motor symptoms in Parkinson’s disease. Prog Brain Res 184:325–341
Chaudhuri KR, Schapira AH (2009) Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8:464–474
Chondrogiorgi M, Tatsioni A, Reichmann H, Konitsiotis S (2014) Dopamine agonist monotherapy in Parkinson’s disease and potential risk factors for dyskinesia: a meta-analysis of levodopa-controlled trials. Eur J Neurol 21:433–440
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 H, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Mehdorn HM, Koringlane 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 (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355:896–908
Eggert KM, Oertel WH, Reichmann H (2012) Leitlinie Parkinson-Syndrome: Diagnostik und Therapie. In: Diener HC, Weimar C and Kommission Leitlinien der Deutschen Gesellschaft für Neurologie (eds). Thieme Verlag, 5th edition
Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K, Parkinson Study Group (2004) Levodopa and the progression of Parkinson’s disease. N Engl J Med 351:2498–2508
Frucht S, Rogers JD, Greene PE, Gordon MF, Fahn S (1999) Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 52:1908–1910
Grosset D, Taurah L, Burn DJ, MacMahon D, Forbes A et al (2007) 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 78:465–469
Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA, Johnston AN, Mellick GD, Herting B, Reichmann H, Hummel T (2009) Prevalence of smell loss in Parkinson’s disease-a multicenter study. Parkinson Rel Disord 15:490–494
Hauser RA, Lew MF, Hurtig HI, Ondo WG, Wojcieszek J, Fitzer-Attas CJ, TEMPO open-label study group (2009) Long-term outcome of early versus delayed rasagiline treatment in early Parkinson’s disease. Mov Disord 24:564–573
Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442
Ingman K, Naukkarinen T, Vahteristo M, Korpela I, Kuoppamäki M, Ellmén J (2012) The effect of different dosing regimens of levodopa/carbidopa/entacapone on plasma levodopa concentrations. Eur J Clin Pharmacol 68:281–289
Iranzo A, Santamaria J, Rye DB, Vallderiola F, Martí MJ, Munoz E, Vilaseca I, Tolosa E (2005) Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology 65:247–252
Kostic V, Przedborski S, Flaster E, Sternic N (1991) Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson’s disease. Neurology 41:202–205
Leentjens AF, van den Akker M, Metsemakers JF, Lousberg R, Verhey FR (2003) Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 18:4144–4418
Martinez-Martin P, Rodriguez-Blaszquez C, Kurtis MM, Chaudhuri KR, NMSS Validation Group (2011) The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord 15:399–406
Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, MacPhee G, Brown RG, Naidu Y, Abe K, Tsuboi Y, MacMahon D, Barone P, Rabey M, Bonuccelli U, Forbes A, Breen K, Tluk S, Olanow CW, Thomas S, Rye D, Hand A, Williams AJ, Ondo W, Chaudhuri KR (2007) Prevalence of nonmotor symptoms in Parkinson’s disease in an international setting: study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 22:1623–1629
Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanaquanas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A, LCIG Horizon Study group (2014) Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomized, controlled, double-blind, double-dummy study. Lancet Neurol 13:141–149
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 (2009) A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med 361:1268–1278
Olanow XC, Kieburtz K, Rascol O, Poewe W, Schapira AH, Emre M, Nissinen H, Leinonen M, Stocchi F, the STRIDE PD investigators (2013) Factors predictive of the development of levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord 28:1064–1071
Parkinson Study Group (1993) Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 328:176–183
Parkinson Study Group (2000) Pramipexole vs levodopa as initial treatment for Parkinson disease: a randomized controlled trial. JAMA 284:1931–1938
Parkinson Study Group (2002) A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 59:1937–1943
Parkinson Study Group (2003) A controlled trial of rotigotine monotherapy in early Parkinson’s disease. Arch Neurol 60:1721–1728
Parkinson Study Group (2005) A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 62:241–248
PD Med Collaborative Group (2014) Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomized trial. Lancet 384:1196–1205
Pogarell O, Gasser T, van Hilten JJ, Spieker S, PollentierS Meier D, Oertel WH (2002) Pramipexole in patients with Parkinson’s disease and marked drug resistant tremor: a randomized, double blind, placebo controlled multicentre study. J Neurol Neurosurg Psychiatry 72:713–720
Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE (2000) A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med 342:1484–1491
Rascol O, Brooks DJ, Melamed E, Oertel W, Poewe W, Stocchi F, Tolosa E, LARGO study group (2005) 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 randomized, double-blind, parallel-group trial. Lancet 365:947–954
Rascol O, Fitzer-Attas CJ, Hauser R, Jankovic J, Lang A, Langston JW, Melamed E, Poewe W, Stocchi F, Tolosa E, Eyal E, Weiss YM, Olanow CW (2011) A double-blind, delayed-start trial of rasagiline in Parkinson’s disease (the ADAGIO study): prespecified and posthoc analyses of the need for additional therapies, changes in UPDRS scoresk and non-motor outcomes. Lancet Neurol 10:415–423
Reichmann H (2010) Clinical criteria for the diagnosis of Parkinson’s disease. Neurodeg Disord 7:284–290
Rizos A (2013) DICE-ET:DA impulse control European evaluation and tolerability study with immediate and extended release dopamine agonists in real life Parkinson’s disease. Poster presentation MDS congress in Sydney
Schapira AH (2007) Treatment options in the modern management of Parkinson’s disease. Arch Neurol 64:1083–1088
Schapira AH, McDermott MP, Barone P, Comella CL, Albrecht S, Hsu HH, Massey DH, Mizuno Y, Poewe W, Rascol O, Marek K (2013) Pramipexole in patients with early Parkinson’s disease (PROUD): a randomized delayed-start trial. Lancet Neurol 12:747–755
Schrag A, Jahanshahi M, Quinn N (2000) What contributes to quality of life in patients with Parkinson’s disease? J Neurol Neurosurg Psychiatry 69:308–312
Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Hälbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seignueret E, Kistner A, Chaynes P, Ory-Magne F, Bfefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltete D, Damier P, Raoul S, Sixel-döring F, Hellwig D, Gharabaghi A, Krüger R, Pinsker MO, Amtage F, Régis JM, Witjas T, Thobois S, Lertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelmann H, Agid Y, Schade-Brittinger C, Deuschl G, EARLYSTIM Study Group (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368:610–622
Sharma JC, Ross IN, Rascol O, Brooks D (2008) relationship between weight, levodopa and dyskinesia: the significance of levodopa dose per kilogram body weight. Eur J Neurol 15:493–496
Sharma JC, Bachmann CG, Linazasano G (2010) Classifying risk factors for dyskinesia in Parkinson’s disease. Parkinsonism Relat Disord 16:490–497
Shoulson I, Oakes D, Fahn S, Lang A, Langston JW, LeWitt P, Olanow CW, Penne JB, Tanner C, Kieburtz K, Rudolph A, Parkinson Study Group (2002) 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 51:604–612
Sommer U, Hummel T, Cormann K, Mueller A, Frasnelli J, Kropp J, Reichmann H (2004) Detection of presymptomatic Parkinson’s disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord 19:1196–1202
Stiasny-Kolster K, Doerr Y, Möller JC, Höffken H, Behr TM, Oertel WH, Mayer G (2005) Combination of idiopathic REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128:126–137
Stocchi F, Vacca IL, Ruggieri S, Olanow CW (2005) Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol 62:905–910
Stocchi F, Rascol O, Kieburtz K, Poewe W, Jankovic J, Tolosa E, Barone P, Lang AE, Olanow WC (2010) initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease. The STRIDE PD study. Ann Neurol 68:18–27
Storch A, Schneider CB, Wolz M, Stürwald Y, Nebe A, Odin P, Mahler A, Fuchs G, Jost WH, Chaudhuri KR, Koch R, Reichmann H, Ebersbach G (2013a) Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology 80:800–809
Storch A, Wolz M, Beuthien-Baumann B, Löhle M, Herting B, Schwanebeck U, Oehme L, van den Hoff J, Perick M, Grhlert X, Kotzerke J, Reichmann H (2013b) Effects of dopaminergic treatment on striatal dopamine turnover in de novo Parkinson disease. Neurology 80:1754–1761
Syed N, Murphy J, Zimmermann T Jr, Mark MH, Sage JI (1998) Ten years’ experience with enteral levodopa infusions for motor fluctuations in Parkinson’s disease. Mov Disord 13:336–338
Verhagen Metman L, DelDotto P, van den Munckhof P, Fang J, Mouradian MM, Chase TN (1998) Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology 50:1323–1326
Voon V, Gao J, Brezing C, Symmonds M, Ekanayake V, Fernandez H, Dolan RJ, Hallett M (2011) Dopamine agonists and risk: impulse control disorders in Parkinson’s disease. Brain 134:1436–1446
Watts RL, Lyons KE, Pahwa R, Sethi K, Stern M, Hauser RA, Olanow W, Gray AM, Earl Adams BNL, 228 Study investigators (2010) Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson’s disease. Mov Disord 25:858–866
Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, Rothlind J, Sagher O, Reda D, Moy CS, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein J, Stoner G, Heemskerk H, Huang GD, CSP 468 Study Group (2009) Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301:63–73
Weinreb O, Amit T, Bar-Am O, Youdim MB (2010) Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol 92:330–344
Weintraub D, David AS, Evans AH, Grant JE, Stacy M (2014) Clinical spectrum of impulse control disorders in Parkinson’s disease. Mov Disord. doi:10.1002/mds.26016 (Epub ahead of print)
Wolters ECh, Braak H (2006) Parkinson’s disease: premotor clinic-pathological correlations. J Neural Transm Suppl 70:309–319
Borgohain R, Szasz J, Stanzione P, Meshram C, Bhatt M, Chirilineau D, Stocchi F, Lucini V, Giuliani R, Forrest E, Rice P, Anand R, Study 018 Investigators (2014b) Two-year, randomized, controlled study of safinamide as add-on to levodopa in mid to late Parkinson’s disease. Mov Disord 29:1273–1280
Ziemssen T, Reichmann H (2010) Treatment of dysautonomia in extrapyramidal disorders. Ther Adv Neurol Disord 3:53–67
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Reichmann, H. Modern treatment in Parkinson’s disease, a personal approach. J Neural Transm 123, 73–80 (2016). https://doi.org/10.1007/s00702-015-1441-1
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DOI: https://doi.org/10.1007/s00702-015-1441-1