Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: the role of opicapone

References

• LeWitt PA. Levodopa therapy for Parkinson’s disease: pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64–72.
   PubMed Web of Science ®Google Scholar
• Olanow CW. Levodopa is the best symptomatic therapy for PD: nothing more, nothing less. Mov Disord. 2019;34(6):812–815.
   PubMed Web of Science ®Google Scholar
• Aquino CC, Fox SH. Clinical spectrum of levodopa-induced complications. Mov Disord. 2015;30(1):80–89.
   PubMed Web of Science ®Google Scholar
• Chaudhuri KR, Jenner P, Antonini A. Should there be less emphasis on levodopa-induced dyskinesia in Parkinson’s disease? Mov Disord. 2019;34(6):816–819.
   PubMed Web of Science ®Google Scholar
• Matthews H, Stamford J, Saha R, et al. Exploring issues around wearing-off and quality of life: the OFF-PARK survey of people with Parkinson’s disease and their care partners. J Parkinsons Dis. 2015;5(3):533–539.
   PubMedGoogle Scholar
• Stacy M. The wearing-off phenomenon and the use of questionnaires to facilitate its recognition in Parkinson’s disease. J Neural Transm. 2010;117(7):837–846.
   PubMed Web of Science ®Google Scholar
• Bjornestad A, Forsaa EB, Pedersen KF, et al. Risk and course of motor complications in a population-based incident Parkinson’s disease cohort. Parkinsonism Relat Disord. 2016;22:48–53.
   PubMed Web of Science ®Google Scholar
• Scott NW, Macleod AD, Counsell CE. Motor complications in an incident Parkinson’s disease cohort. Eur J Neurol. 2016;23(2):304–312.
   PubMed Web of Science ®Google Scholar
• Kim H-J, Mason S, Foltynie T, et al. Motor complications in Parkinson’s disease: 13-Year follow-up of the CamPaIGN Cohort. Mov Disord. 2020;35(1):185–190.
   PubMed Web of Science ®Google Scholar
• LeWitt PA, Chaudhuri KR. Unmet needs in Parkinson disease: motor and non-motor. Parkinsonism Relat Disord. 2020;80(Suppl 1):S7–S12.
   PubMed Web of Science ®Google Scholar
• 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(2):224–230.
   PubMed Web of Science ®Google Scholar
• Hechtner MC, Vogt T, Zollner Y, et al. Quality of life in Parkinson’s disease patients with motor fluctuations and dyskinesias in five European countries. Parkinsonism Relat Disord. 2014;20:969–974.
   PubMed Web of Science ®Google Scholar
• Wu J, Lim E-C, Nadkarni NV, et al. The impact of levodopa therapy-induced complications on quality of life in Parkinson’s disease patients in Singapore. Sci Rep. 2019;9(1):9248.
   PubMed Web of Science ®Google Scholar
• Soh S-E, Morris ME, McGinley JL. Determinants of health-related quality of life in Parkinson’s disease: a systematic review. Parkinsonism Relat Disord. 2011;17(1):1–9.
   PubMed Web of Science ®Google Scholar
• Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study. Brain. 2000;123(Pt 11):2297–2305.
   PubMed Web of Science ®Google Scholar
• Michael J Fox Foundation. Capturing and elevating the patient voice; 2014. [cited 2021 Aug]. Available from: https://www.michaeljfox.org/foundation/news-detail.php?capturing-and-elevating-the-patient-voice
   Google Scholar
• Pahwa R, Lyons KE. Levodopa-related wearing-off in Parkinson’s disease: identification and management. Curr Med Res Opin. 2009;25(4):841–849.
   PubMed Web of Science ®Google Scholar
• Hauser RA, McDermott MP, Messing S. Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Arch Neurol. 2006;63(12):1756–1760.
   PubMed Web of Science ®Google Scholar
• Olanow CW, Kieburtz K, Rascol O, et al. Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson’s disease. Mov Disord. 2013;28(8):1064–1071.
   PubMed Web of Science ®Google Scholar
• Kadastik-Eerme L, Taba N, Asser T, et al. Factors associated with motor complications in Parkinson’s disease. Brain Behav. 2017;7(10):e00837–e.
   PubMed Web of Science ®Google Scholar
• Stocchi F. The levodopa wearing-off phenomenon in Parkinson’s disease: pharmacokinetic considerations. Expert Opin Pharmacother. 2006;7(10):1399–1407.
   PubMedGoogle Scholar
• Stocchi F, Jenner P, Obeso JA. When do levodopa motor fluctuations first appear in Parkinson’s disease? Eur Neurol. 2010;63(5):257–266.
   PubMed Web of Science ®Google Scholar
• Olanow CW, Kieburtz K, Odin P, et al. 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):141–149.
   PubMed Web of Science ®Google Scholar
• Antonini A, Stoessl AJ, Kleinman LS, et al. Developing consensus among movement disorder specialists on clinical indicators for identification and management of advanced Parkinson’s disease: a multi-country Delphi-panel approach. Curr Med Res Opin. 2018;34(12):2063–2073.
   PubMed Web of Science ®Google Scholar
• Stocchi F, Giorgi L, Hunter B, et al. PREPARED: comparison of prolonged and immediate release ropinirole in advanced Parkinson’s disease. Mov Disord. 2011;26(7):1259–1265.
   PubMed Web of Science ®Google Scholar
• Schapira AH, Barone P, Hauser RA, et al. Extended-release pramipexole in advanced Parkinson disease: a randomized controlled trial. Neurology. 2011;77(8):767–774.
   PubMed Web of Science ®Google Scholar
• Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2018;17(9):749–759.
   PubMed Web of Science ®Google Scholar
• LeWitt PA, Lyons KE, Pahwa R. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology. 2007;68(16):1262–1267.
   PubMed Web of Science ®Google Scholar
• 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(10):929–937.
   PubMed Web of Science ®Google Scholar
• Jenner P, Mori A, Aradi SD, et al. Istradefylline – a first generation adenosine A2A antagonist for the treatment of Parkinson’s disease. Expert Rev Neurother. 2021;21:317–333.
   PubMed Web of Science ®Google Scholar
• Elmer LW, Juncos JL, Singer C, et al. Pooled analyses of Phase III studies of ADS-5102 (Amantadine) extended-release capsules for Dyskinesia in Parkinson’s disease. CNS Drugs. 2018;32(4):387–398.
   PubMed Web of Science ®Google Scholar
• Fox SH, Katzenschlager R, Lim SY, et al. International Parkinson and movement disorder society evidence-based medicine review: update on treatments for the motor symptoms of Parkinson’s disease. Mov Disord. 2018;33(8):1248–1266.
   PubMed Web of Science ®Google Scholar
• Keating GM, Lyseng-Williamson KA. Tolcapone: a review of its use in the management of Parkinson’s disease. CNS Drugs. 2005;19(2):165–184.
   PubMed Web of Science ®Google Scholar
• Kaakkola S. Problems with the present inhibitors and a relevance of new and improved COMT inhibitors in Parkinson’s disease. Int Rev Neurobiol. 2010;95:207–225.
   PubMed Web of Science ®Google Scholar
• Kiss LE, Soares-da-Silva P. Medicinal chemistry of catechol O-methyltransferase (COMT) inhibitors and their therapeutic utility. J Med Chem. 2014;57(21):8692–8717.
   PubMed Web of Science ®Google Scholar
• Cotzias GC. L-Dopa for Parkinsonism. N Engl J Med. 1968;278(11):630.
   PubMed Web of Science ®Google Scholar
• Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351(24):2498–2508.
   PubMed Web of Science ®Google Scholar
• Verschuur CVM, Suwijn SR, Boel JA, et al. Randomized delayed-start trial of levodopa in Parkinson’s disease. N Engl J Med. 2019;380(4):315–324.
   PubMed Web of Science ®Google Scholar
• Hauser RA. Levodopa: past, present, and future. Eur Neurol. 2009;62(1):1–8.
   PubMed Web of Science ®Google Scholar
• Calne DB, Reid JL, Vakil SD, et al. Idiopathic Parkinsonism treated with an extracerebral decarboxylase inhibitor in combination with levodopa. Br Med J. 1971;3(5777):729–732.
   PubMed Web of Science ®Google Scholar
• Nutt JG, Woodward WR, Anderson JL. The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: the mechanism of action in the treatment of parkinsonism. Ann Neurol. 1985;18(5):537–543.
   PubMed Web of Science ®Google Scholar
• Lieberman A, Goodgold A, Jonas S, et al. Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson’s disease. Neurology. 1975;25(10):911–916.
   PubMed Web of Science ®Google Scholar
• Markham C, Diamond SG, Treciokas LJ. Carbidopa in Parkinson disease and in nausea and vomiting of levodopa. Arch Neurol. 1974;31(2):128–133.
   PubMed Web of Science ®Google Scholar
• Gershanik OS. Improving l-dopa therapy: the development of enzyme inhibitors. Mov Disord. 2015;30(1):103–113.
   PubMed Web of Science ®Google Scholar
• Deleu D, Northway MG, Hanssens Y. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet. 2002;41(4):261–309.
   PubMed Web of Science ®Google Scholar
• Karhunen T, Tilgmann C, Ulmanen I, et al. Distribution of catechol-O-methyltransferase enzyme in rat tissues. J Histochem Cytochem. 1994;42(8):1079–1090.
   PubMed Web of Science ®Google Scholar
• Nutt JG, Woodward WR, Gancher ST, et al. 3-0-methyldopa and the response to levodopa in Parkinson’s disease. Ann Neurol. 1987;21:584–588.
   PubMed Web of Science ®Google Scholar
• Tohgi H, Abe T, Kikuchi T, et al. The significance of 3-O-methyldopa concentrations in the cerebrospinal fluid in the pathogenesis of wearing-off phenomenon in Parkinson’s disease. Neurosci Lett. 1991;132(1):19–22.
   PubMed Web of Science ®Google Scholar
• Mena MA, Muradas V, Bazan E, et al. Pharmacokinetics of L-dopa in patients with Parkinson’s disease. Adv Neurol. 1987;45:481–486.
   PubMedGoogle Scholar
• Müller T, van Laar T, Cornblath DR, et al. Peripheral neuropathy in Parkinson’s disease: levodopa exposure and implications for duodenal delivery. Parkinsonism Relat Disord. 2013;19(5):501–507.
   PubMed Web of Science ®Google Scholar
• Kaakkola S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson’s disease. Drugs. 2000;59(6):1233–1250.
   PubMed Web of Science ®Google Scholar
• Bonifácio MJ, Palma PN, Almeida L, et al. Catechol-O-methyltransferase and its inhibitors in Parkinson’s disease. CNS Drug Rev. 2007;13(3):352–379.
   PubMedGoogle Scholar
• Kaakkola S, Gordin A, Mannisto PT. General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase. Gen Pharmacol. 1994;25(5):813–824.
   PubMedGoogle Scholar
• Artusi CA, Sarro L, Imbalzano G, et al. Safety and efficacy of tolcapone in Parkinson’s disease: systematic review. Eur J Clin Pharmacol. 2021;77(6):817–829.
   PubMed Web of Science ®Google Scholar
• Olanow CW, Watkins PB. Tolcapone: an efficacy and safety review (2007). Clin Neuropharmacol. 2007;30(5):287–294.
   PubMed Web of Science ®Google Scholar
• Kiss LE, Ferreira HS, Torrao L, et al. Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase. J Med Chem. 2010;53(8):3396–3411.
   PubMed Web of Science ®Google Scholar
• Palma PN, Bonifacio MJ, Loureiro AI, et al. Computation of the binding affinities of catechol-O-methyltransferase inhibitors: multisubstate relative free energy calculations. J Comput Chem. 2012;33(9):970–986.
   PubMed Web of Science ®Google Scholar
• Bonifacio MC, Torrao M, Loureiro AI, et al. Opicapone: characterization of a novel peripheral long-acting catechol-O-methyltransferase inhibitor. Parkinsonism Relat Disord. 2012;18(suppl 2):S125.
   Google Scholar
• Bonifacio MJ, Torrao L, Loureiro AI, et al. Pharmacological profile of opicapone, a third-generation nitrocatechol catechol-O-methyl transferase inhibitor, in the rat. Br J Pharmacol. 2015;172(7):1739–1752.
   PubMed Web of Science ®Google Scholar
• Bonifacio MJ, Sutcliffe JS, Torrao L, et al. Brain and peripheral pharmacokinetics of levodopa in the cynomolgus monkey following administration of opicapone, a third generation nitrocatechol COMT inhibitor. Neuropharmacology. 2014;77:334–341.
   PubMed Web of Science ®Google Scholar
• Bonifacio MJ, Sousa F, Soares-da-Silva P. Opicapone enhances the reversal of MPTP-induced Parkinson-like syndrome by levodopa in cynomolgus monkeys. Eur J Pharmacol. 2021;892:173742.
   PubMed Web of Science ®Google Scholar
• Tissot R, Bartholini G, Pletscher A. Drug-induced changes of extracerebral dopa metabolism in man. Arch Neurol. 1969;20(2):187–190.
   PubMedGoogle Scholar
• Rocha JF, Falcao A, Santos A, et al. Effect of opicapone and entacapone upon levodopa pharmacokinetics during three daily levodopa administrations. Eur J Clin Pharmacol. 2014;70(9):1059–1071.
   PubMed Web of Science ®Google Scholar
• Almeida L, Rocha JF, Falcao A, et al. Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor. Clin Pharmacokinet. 2013;52(2):139–151.
   PubMed Web of Science ®Google Scholar
• Loewen G, Lewitt P, Olanow CW, et al. Pharmacokinetics of opicapone and effect on COMT and levodopa pharmacokinetics in patients with Parkinson’s disease [abstract]. Mov Disord. 2019;34(suppl 2); [cited 2021 Aug]. Available from: https://www.mdsabstracts.org/abstract/pharmacokinetics-of-opicapone-and-effect-on-comt-and-levodopa-pharmacokinetics-in-patients-with-parkinsons-disease/
   Google Scholar
• Stocchi F, Vacca L, Ruggieri S, et al. Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Arch Neurol. 2005;62(6):905–910.
   PubMedGoogle Scholar
• Brusa L, Pierantozzi M, Bassi A, et al. Temporal administration of entacapone with slow release L-dopa: pharmacokinetic profile and clinical outcome. Neurol Sci. 2004;25(2):53–56.
   PubMed Web of Science ®Google Scholar
• Myllyla VV, Sotaniemi KA, Illi A, et al. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics of levodopa and on cardiovascular responses in patients with Parkinson’s disease. European Journal Clinical Pharmacology. 1993;45:419–423.
   Google Scholar
• Falcão A, Santos A, Ferreira JJ, et al. Decision-making process for opicapone’s bedtime regimen [abstract]. Mov Disord. 2017;32(Suppl 2); [cited 2021 Aug]. Available from: https://www.mdsabstracts.org/abstract/decision-making-process-for-opicapones-bedtime-regimen/
   Google Scholar
• NICE. Parkinson’s disease with end-of-dose motor fluctuations: opicapone. Evidence summary [ES9] Published date; 2017 Mar 21. [cited 2021 Aug]. Available from: https://www.nice.org.uk/advice/es9/chapter/Estimated-impact-for-the-NHS
   Google Scholar
• de la Fuente-Fernandez R, Lu JQ, Sossi V, et al. Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson’s disease: PET evidence of increased dopamine turnover. Ann Neurol. 2001;49(3):298–303.
   PubMed Web of Science ®Google Scholar
• Stocchi F, Olanow CW. Continuous dopaminergic stimulation in early and advanced Parkinson’s disease. Neurology. 2004;62(1 Suppl 1):S56–63.
   PubMed Web of Science ®Google Scholar
• Fabbri M, Ferreira JJ, Lees A, et al. Opicapone for the treatment of Parkinson’s disease: a review of a new licensed medicine. Mov Disord. 2018;33(10):1528–1539.
   PubMed Web of Science ®Google Scholar
• Lees AJ, Ferreira J, Rascol O, et al. Opicapone for the management of end-of-dose motor fluctuations in patients with Parkinson’s disease treated with L-DOPA. Expert Rev Neurother. 2017;17(7):649–659.
   PubMed Web of Science ®Google Scholar
• Scott LJ. Opicapone: a review in Parkinson’s disease. CNS Drugs. 2021;35(1):121–131.
   PubMed Web of Science ®Google Scholar
• Ferreira JJ, Lees A, Rocha JF, et al. Opicapone as an adjunct to levodopa in patients with Parkinson’s disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial. Lancet Neurol. 2016;15(2):154–165.
   PubMed Web of Science ®Google Scholar
• Lees AJ, Ferreira J, Rascol O, et al. Opicapone as adjunct to levodopa therapy in patients with parkinson disease and motor fluctuations: a randomized clinical trial. JAMA Neurol. 2017;74(2):197–206.
   PubMed Web of Science ®Google Scholar
• Takeda A, Takahashi R, Tsuboi Y, et al. Randomized, controlled study of opicapone in Japanese Parkinson’s patients with motor fluctuations. Mov Disord. 2021;36(2):415–423.
   PubMed Web of Science ®Google Scholar
• Ferreira JJ, Lees A, Rocha JF, et al. Long-term efficacy of opicapone in fluctuating Parkinson’s disease patients: a pooled analysis of data from two phase 3 clinical trials and their open-label extensions. Eur J Neurol. 2019;26(7):953–960.
   PubMed Web of Science ®Google Scholar
• Deane KH, Spieker S, Clarke CE. Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson’s disease. Cochrane Database Syst Rev. 2004;4:CD004553.
   PubMedGoogle Scholar
• Schade S, Mollenhauer B, Trenkwalder C. Levodopa equivalent dose conversion factors: an updated proposal including opicapone and safinamide. Mov Disord Clin Pract. 2020;7(3):343–345.
   PubMed Web of Science ®Google Scholar
• Ferreira JJ, Lees AJ, Poewe W, et al. Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease. Neurology. 2018;90(21):e1849–e57.
   PubMed Web of Science ®Google Scholar
• Hansen RN, Suh K, Serbin M, et al. Cost-effectiveness of opicapone and entacapone in reducing OFF-time in Parkinson’s disease patients treated with levodopa/carbidopa. J Med Econ. 2021;24(1):563–569.
   PubMed Web of Science ®Google Scholar
• Findley LJ, Wood E, Lowin J, et al. The economic burden of advanced Parkinson’s disease: an analysis of a UK patient dataset. J Med Econ. 2011;14(1):130–139.
   PubMedGoogle Scholar
• Thach A, Jones E, Pappert E, et al. Real-world assessment of “OFF” episode-related healthcare resource utilization among patients with Parkinson’s disease in the United States. J Med Econ. 2021;24(1):540–549.
   PubMed Web of Science ®Google Scholar
• Reichmann H, Lees A, Rocha JF, et al., investigators O. Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study. Transl Neurodegener. 2020;9(1):9.
   PubMed Web of Science ®Google Scholar
• Hauser RA, Auinger P. Determination of minimal clinically important change in early and advanced Parkinson’s disease. Mov Disord. 2011;26(5):813–818.
   PubMed Web of Science ®Google Scholar
• Lees A, Ferreira JJ, Rocha JF, et al. Safety profile of opicapone in the management of Parkinson’s disease. J Parkinsons Dis. 2019;9:733–740.
   PubMedGoogle Scholar
• Vokurka P, Barron A, Sumaria S, et al. Opicapone efficacy and tolerability in Parkinson’s disease patients reporting insufficient benefit/failure of entacapone. Mov Disord Clin Pract. 2020;7(8):955–960.
   PubMed Web of Science ®Google Scholar
• Lees AJ. Evidence-based efficacy comparison of tolcapone and entacapone as adjunctive therapy in Parkinson’s disease. CNS Neurosci Ther. 2008;14(1):83–93.
   PubMed Web of Science ®Google Scholar
• Muller T. Catechol-o-methyltransferase inhibitors in Parkinson’s disease. Drugs. 2015;75(2):157–174.
   PubMed Web of Science ®Google Scholar
• Stocchi F, Antonini A, Barone P, et al. Early DEtection of wEaring off in Parkinson disease: the DEEP study. Parkinsonism Relat Disord. 2014;20(2):204–211.
   PubMed Web of Science ®Google Scholar
• Stacy M, Bowron A, Guttman M, et al. Identification of motor and nonmotor wearing-off in Parkinson’s disease: comparison of a patient questionnaire versus a clinician assessment. Mov Disord. 2005;20(6):726–733.
   PubMed Web of Science ®Google Scholar
• Colombo D, Abbruzzese G, Antonini A, et al. The “gender factor” in wearing-off among patients with Parkinson’s disease: a post hoc analysis of DEEP study. ScientificWorldJournal. 2015;2015:787451.
   PubMedGoogle Scholar
• Lees A, Ferreira JJ, Rocha JF, et al. Safety profile of opicapone in the management of Parkinson’s disease. J Parkinsons Dis. 2019;9(4):733–740.
   PubMedGoogle Scholar
• Ebersbach G, Ferreira J, Antonini A, et al. Opicapone’s added benefit as a first-line adjunctive therapy to levodopa and when used promptly in the motor fluctuations spectrum of Parkinson’s disease: a post-hoc analysis of BIPARK-I and II [abstract]. Mov Disord. 2020;35(suppl 1); [cited 2021 Aug]. Available from: https://www.mdsabstracts.org/abstract/opicapones-added-benefit-as-a-first-line-adjunctive-therapy-to-levodopa-and-when-used-promptly-in-the-motor-fluctuations-spectrum-of-parkinsons-disease-a-post-hoc-analysis-of-bipark/
   PubMed Web of Science ®Google Scholar
• Hauser RA, Gordon MF, Mizuno Y, et al. Minimal clinically important difference in Parkinson’s disease as assessed in pivotal trials of pramipexole extended release. Parkinsons Dis. 2014;2014:467131.
   PubMed Web of Science ®Google Scholar
• Nissinen H, Kuoppamaki M, Leinonen M, et al. Early versus delayed initiation of entacapone in levodopa-treated patients with Parkinson’s disease: a long-term, retrospective analysis. Eur J Neurol. 2009;16(12):1305–1311.
   PubMed Web of Science ®Google Scholar
• Hauser RA, Deckers F, Lehert P. Parkinson’s disease home diary: further validation and implications for clinical trials. Mov Disord. 2004;19(12):1409–1413.
   PubMed Web of Science ®Google Scholar
• Goetz CG, Tilley BC, Shaftman SR, et al. Movement disorder society-sponsored revision of the Unified Parkinson’s disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23(15):2129–2170.
   PubMed Web of Science ®Google Scholar
• Chaudhuri KR, Schrag A, Weintraub D, et al. The movement disorder society nonmotor rating scale: initial validation study. Mov Disord. 2020;35(1):116–133.
   PubMed Web of Science ®Google Scholar
• Jenkinson C, Fitzpatrick R, Peto V, et al. The PDQ-8: development and validation of a short-form parkinson’s disease questionnaire. Psychol Health. 1997;12(6):805–814.
   Web of Science ®Google Scholar
• Guy W. Clinical global impressions. ECDEU assessment manual for psychopharmacology. Rockville, MD, Washington, DC: Department of Health, Education, and Welfare; 1976. p. 218–222.
   Google Scholar
• Jenner P, McCreary AC, Scheller DK. Continuous drug delivery in early- and late-stage Parkinson’s disease as a strategy for avoiding dyskinesia induction and expression. J Neural Transm. 2011;118(12):1691–1702.
   PubMed Web of Science ®Google Scholar
• Olanow CW, Obeso JA, Stocchi F. Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol. 2006;5(8):677–687.
   PubMed Web of Science ®Google Scholar
• Olanow CW, Obeso JA, Stocchi F. Drug Insight: continuous dopaminergic stimulation in the treatment of Parkinson’s disease. Nat Clin Pract Neurol. 2006;2(7):382–392.
   PubMedGoogle Scholar
• Picconi B, Piccoli G, Calabresi P. Synaptic dysfunction in Parkinson’s disease. Adv Exp Med Biol. 2012;970:553–572.
   PubMed Web of Science ®Google Scholar
• Stocchi F, Rascol O, Kieburtz K, 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 Web of Science ®Google Scholar
• Smith LA, Jackson MJ, Al-Barghouthy G, et al. Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates. Mov Disord. 2005;20(3):306–314.
   PubMed Web of Science ®Google Scholar
• Muhlack S, Herrmann L, Salmen S, et al. Fewer fluctuations, higher maximum concentration and better motor response of levodopa with catechol-O-methyltransferase inhibition. J Neural Transm. 2014;121(11):1357–1366.
   PubMed Web of Science ®Google Scholar
• Kuoppamaki M, Korpela K, Marttila R, et al. Comparison of 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(5):443–455.
   PubMed Web of Science ®Google Scholar
• Ferreira JJ, Poewe W, Rascol O, et al. Study-design to assess the effect of opicapone on levodopa PK at different levodopa-optimized treatment regimens [Abstract]. Eur J Neurol. 2021;28(1):718.
   Google Scholar
• Waters CH, Kurth M, Bailey P, et al. Tolcapone in stable Parkinson’s disease: efficacy and safety of long-term treatment. The Tolcapone Stable Study Group. Neurology. 1997;49(3):665–671.
   PubMed Web of Science ®Google Scholar
• Hauser RA, Panisset M, Abbruzzese G, et al. Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson’s disease. Mov Disord. 2009;24(4):541–550.
   PubMed Web of Science ®Google Scholar
• Brooks DJ, Sagar H. 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):1071–1079.
   PubMed Web of Science ®Google Scholar
• Poewe WH, Deuschl G, Gordin A, et al. Efficacy and safety of entacapone in Parkinson’s disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study). Acta Neurol Scand. 2002;105(4):245–255.
   PubMed Web of Science ®Google Scholar
• Early ParkinSon wIth L-DOPA and OpicapoNe [EPSILON] study. EudraCT number 2020-005011-52. [ cited 2021 Jul 25]. Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-005011-52/CZ
   Google Scholar
• Opicapone Treatment Initiation Open-Label Study (OPTI-ON). NCT number NCT04787965. [ cited 2021 Jul 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT04787965
   Google Scholar
• Kleiner G, Fernandez HH, Chou KL, et al. Non-Motor Fluctuations in Parkinson’s Disease: validation of the Non-Motor Fluctuation Assessment Questionnaire. Mov Disord. 2021;36(6):1392–1400.
   PubMed Web of Science ®Google Scholar
• OpicApone Sleep dISorder (OASIS) study. EudraCT number 2020-001176-15. [ cited 2021 Jul 25]. Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001176-15/DE
   Google Scholar
• Storch A, Schneider CB, Wolz M, et al. Nonmotor fluctuations in Parkinson disease: severity and correlation with motor complications. Neurology. 2013;80(9):800–809.
   PubMed Web of Science ®Google Scholar
• Antonini A, Tinazzi M, Abbruzzese G, et al. Pain in Parkinson’s disease: facts and uncertainties. Eur J Neurol. 2018;25(7):917–e69.
   PubMed Web of Science ®Google Scholar
• Nebe A, Ebersbach G. Pain intensity on and off levodopa in patients with Parkinson’s disease. Mov Disord. 2009;24(8):1233–1237.
   PubMed Web of Science ®Google Scholar
• OpiCapone Effect on motor fluctuations and pAiN [OCEAN] study. EudraCT number 2020-001175-32. [ cited 2021 Jul 25]. Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001175-32/PT
   Google Scholar
• Hauser RA. Levodopa/carbidopa/entacapone (Stalevo). Neurology. 2004;62(1 Suppl 1):S64–71.
   PubMed Web of Science ®Google Scholar
• Öthman M, Widman E, Nygren I, et al. Initial Experience of the Levodopa-Entacapone-Carbidopa Intestinal Gel in Clinical Practice. J Pers Med. 2021;11(4):254.
   PubMed Web of Science ®Google Scholar
• Poewe W, Antonini A. Novel formulations and modes of delivery of levodopa. Mov Disord. 2015;30(1):114–120.
   PubMed Web of Science ®Google Scholar
• Giladi N, Caraco Y, Gurevich T, et al. ND0612 (levodopa/carbidopa for subcutaneous infusion) achieves stable levodopa plasma levels when administered in low and high doses in patients with PD [abstract]. Mov Disord. 2017;32(suppl 2). [cited Aug 2021]. http://www.mdsabstracts.org/abstract/nd0612-levodopacarbidopa-for-subcutaneous-infusion-achieves-stable-levodopa-plasma-levels-when-administered-in-low-and-high-doses-in-patients-with-pd/.
   Google Scholar
• Leta V, Van Wamelen DJ, Sauerbier A, et al. Opicapone and levodopa-carbidopa intestinal gel infusion: the way forward towards cost savings for healthcare systems? J Parkinsons Dis. 2020;10(4):1535–1539.
   PubMedGoogle Scholar