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Chapter 22 - Conventional Pharmacotherapy in Parkinson’s Disease

from Section 2: - Hypokinetic Movement Disorders

Published online by Cambridge University Press:  07 January 2025

By
Erik Ch. Wolters
Edited by
Erik Ch. Wolters  and
Christian R. Baumann
Erik Ch. Wolters
Affiliation:
Universität Zürich
Christian R. Baumann
Affiliation:
Universität Zürich
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Summary

This chapter deals with the pharmacotherapy of motor clinical hallmarks in Parkinson’s disease (PD), plus other PD and/or its intervention-related signs and symptoms. The treatment of PD-related non-dopaminergic symptoms such as mainly autonomic, neuropsychiatric and sleep–wake disorders are extensively dealt with in other chapters, so the pharmacotherapy of these disorders are only be discussed briefly. Autonomic non-motor fluctuations comprise cardiovascular (orthostatic hypotension), urogenital (detrusor over- and underactivity-related problems, e.g., urgency, frequency, nocturia, hesitation and straining), and gastrointestinal manifestations (sialorrhea, dysphagia, delayed gastric emptying, constipation). Depression and (mild) cognitive impairment are the most important mainly direct PD-related neuropsychiatric disorders, whereas impulse control disorders, as well as dementia and psychosis, are frequently seen as dopaminomimetic adverse events. Sleep–wake disorders with parasomnias are also characteristic non-motor symptoms in PD. The tailored pharmacologic strategies in these non-dopaminergic symptoms are discussed in detail.

Keywords

(Non) dopaminergic strategiesglutamate/cholinergic/adenosine 2A receptor antagonistsstrategies in PD-related autonomic/neuropsychiatric/sleep disorders
Type
Chapter
Information
International Compendium of Movement Disorders , pp. 264 - 279
Publisher: Cambridge University Press
Print publication year: 2025

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References

Birkmayer, W, Hornykiewicz, O. The l-3,4-dioxyphenylalanine (l-DOPA) effect in Parkinson–akinesia. Wien Klin Wochenschrift 1961;73:787–788.Google Scholar
Hornykiewicz, O. Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 1966;18:925–964.Google ScholarPubMed
Uitti, RJ, Ahlskog, JE, Maraganore, DM, et al. Levodopa therapy and survival in idiopathic Parkinson’s disease: Olmsted County Project. Neurology 1993;43:1918–1926.CrossRefGoogle ScholarPubMed
Pandey, S, Srivanitchapoom, P. Levodopa-induced dyskinesia: clinical features, pathophysiology, and medical management. Ann Indian Acad Neurol 2017;20:190–198.CrossRefGoogle ScholarPubMed
Jenner, P. Molecular mechanisms of L-DOPA-induced dyskinesia. Nat Rev Neurosci 2008;9:665–677.CrossRefGoogle ScholarPubMed
Braak, H, Del Tredici, K, Rüb, U, et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211.CrossRefGoogle ScholarPubMed
Wolters, ECh, Braak, H. Parkinson’s disease: premotor clinicopathological correlations. J Neural Transm 2006;S70:309–320.Google Scholar
Henchcliffe, C, Parmar, M. Repairing the brain: cell replacement using stem cell-based technologies. J Parkinson’s Disease 2018;8:S131–S137.CrossRefGoogle ScholarPubMed
Bjorklund, P. Repairing the brain: gene therapy. J Parkinson’s Disease 2018;8:S123–S130.CrossRefGoogle ScholarPubMed
Wolters, EC, Strekalova, T, de Munter, JPJM, Kramer, BW. Naive BM-derived stem cells (Neuro-Cells) may modify acute and chronic neurodegenerative disorders by modulating macrophage behaviors. Ageing Neur Dis 2021;1:3.Google Scholar
Goudreau, JL, Ahlskog, JE. Symptomatic treatment of Parkinson’s disease: levodopa. In: Pfeiffer, RF, Wszolek, ZK, Ebadi, M, eds. Parkinson’s Disease, 2nd ed. Boca Raton: CRC Press; 2013: 847–859.Google Scholar
Pinder, RM, Brogden, RN, Sawyer, PR, Speight, TM, Avery, GS. Levodopa and decarboxylase inhibitors: a review of their clinical pharmacology and use in the treatment of parkinsonism. Drugs 1976;11:329–377.CrossRefGoogle ScholarPubMed
Grosset, DG, Dhall, R, GurevichcJ, A, et al. Inhaled levodopa in Parkinson’s disease patients with OFF periods: a randomized 12-month pulmonary safety study. Parkinsonism Relat Dis 2020;71:4–10.CrossRefGoogle ScholarPubMed
Valldeoriola, F, Catalán, MJ, Escamilla-Sevilla, F, et al. Patient and caregiver outcomes with levodopa–carbidopa intestinal gel in advanced Parkinson’s disease. NPJ Parkinsons Dis 2021;7:108.CrossRefGoogle ScholarPubMed
Giladi, N, Gurevich, T, Djaldetti, R, et al. ND0612 (levodopa/carbidopa for subcutaneous infusion: a randomized, placebo-controlled phase 2 study. Parkinsonism Relat Dis 2021;91:139–145.CrossRefGoogle ScholarPubMed
Olanow, CW, Espay, AJ, Stocchi, F. Continuous subcutaneous levodopa delivery for Parkinson’s disease: a randomized study. J Parkinsons Dis 2021;11:177–186.CrossRefGoogle ScholarPubMed
Siddiqi, SH, Abraham, NK, Geiger, CL, et al. The human experience with intravenous levodopa. Front Pharmacol 2016;6:307.CrossRefGoogle ScholarPubMed
Brooks, DJ. Dopamine agonists: their role in the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2000;68:685–690.CrossRefGoogle ScholarPubMed
Zanettini, R, Antonini, A, Gatto, G, et al. Valvular heart disease and the use of dopamine agonists for Parkinson’s disease. N Engl J Med 2007;356:39–46.CrossRefGoogle ScholarPubMed
Yamamoto, M, Uesugi, T, Nakayama, T. Dopamine agonists and cardiac valvulopathy in Parkinson disease: a case–control study. Neurology 2006;67:1225–1229.CrossRefGoogle ScholarPubMed
Ruan, X, Lin, F, Wu, D, et al. Comparative efficacy and safety of dopamine agonists in advanced Parkinson’s disease with motor fluctuations: a systematic review and network meta-analysis of double-blind randomized controlled trials. Front Neurosci 2021;15:728083.CrossRefGoogle ScholarPubMed
Gerlach, M, Double, K, Arzberger, T, et al. Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm 2003;110:1119–1127.CrossRefGoogle ScholarPubMed
Calne, DB, Teychenne, PF, Claveria, LE, et al. Bromocriptine in Parkinsonism. BMJ 1974;4:442–444.CrossRefGoogle ScholarPubMed
Gershanik, OS. Cabergoline. In: Pahwa, R, Lyons, KE, Koller, W, eds., Therapy of Parkinson’s Disease, 3rd ed. Boca Raton: CRC Press; 2004.Google Scholar
Li, B-D, Cui, J-J, Song, J, et al. Comparison of the efficacy of different drugs on non-motor symptoms of Parkinson’s disease: a network meta-analysis. Cell Physiol Biochem 2018;45:119–130.CrossRefGoogle ScholarPubMed
Carbone, F, Djamshidian, A, Seppi, K, Poewe, W. Apomorphine for Parkinson’s disease: efficacy and safety of current and new formulations. CNS Drugs 2019;33:905–918.CrossRefGoogle ScholarPubMed
Hattori, N, Mochizuki, H, Hasegawa, K, et al. Ropinirole patch versus placebo, ropinirole extended-release tablet in advanced Parkinson’s disease. Mov Disord 2020;35:1565–1573.CrossRefGoogle ScholarPubMed
Fishman, PS. Pramipexole and its extended release formulation for Parkinson’s disease. J Cent Nerv Syst Dis 2011;23:169–178.Google Scholar
Olanow, CW, Kieburtz, K, Leinonen, M, et al. A randomized trial of a low-dose rasagiline and pramipexole combination (P2B001) in early Parkinson’s disease. Mov Disord 2017;32:783–789.CrossRefGoogle ScholarPubMed
Md, S, Karim, S, Saker, SR, et al. Current status and challenges in rotigotine delivery. Curr Pharm Des 2020;26(19):2222–2232.CrossRefGoogle ScholarPubMed
Antonini, A, Bernardi, L, Calandrella, D, Mancini, F, Plebani, M. Rotigotine transdermal patch in the management of Parkinson’s disease (PD) and its night-time use for PD-related sleep disorders. Funct Neurol 2010;25:21–25.Google ScholarPubMed
Rizek, P, Kumar, N, Jog, MS. An update on the diagnosis and treatment of Parkinson disease. CMAJ 2016;188:1157–1165.CrossRefGoogle ScholarPubMed
Yazdchi Marandi, M, Ayromlou, H, Najmi, S, et al. Prevalence of levodopa-induced peripheral neuropathy in patients with Parkinson’s disease and vitamin B12 deficiency. Galen Med J 2021;10:e1837.CrossRefGoogle Scholar
Feng Qiu, F, Wu, Y, Cao, H, et al. Changes of peripheral nerve function and vitamin B12 level in people with Parkinson’s disease. Front Neurol 2020;11:549159.Google Scholar
Poewe, W, Antonini, A, Zijlmans, JC, Burkhard, PR, Vingerhoets, F. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging 2010;5:229–238.Google ScholarPubMed
Shetty, AS, Bhatia, KP, Lang, AE. Dystonia and Parkinson’s disease: what is the relationship? Neurobiol Dis 2019;132:104462.CrossRefGoogle ScholarPubMed
Gao, C, Liu, J, Tan, Y, Chen, S. Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments. Transl Neurodegener 2020;9:12.CrossRefGoogle ScholarPubMed
Fabbrini, A, Guerra, A. Pathophysiological mechanisms and experimental pharmacotherapy for l-DOPA-induced dyskinesia. J Exp Pharmacol 2021;13:469–485.CrossRefGoogle ScholarPubMed
Wolters, EC, van der Werf, YD, van den Heuvel, OA. Parkinson’s disease-related disorders in the impulsive–compulsive spectrum. J Neurol 2008;255:48–56.CrossRefGoogle ScholarPubMed
Zesiewicz, TA, Hauser, RA. Sleep attacks and dopamine agonists for Parkinson’s disease. CNS Drugs 2003;17:593–600.CrossRefGoogle ScholarPubMed
Koschel, J, Ray Chaudhuri, K, Tönges, L, et al. Implications of dopaminergic medication withdrawal in Parkinson’s disease. J Neural Transm (Vienna) 2022;129:1169–1178.CrossRefGoogle ScholarPubMed
Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002;59:1937–1943.CrossRefGoogle Scholar
Parkinson Study Group. Does levodopa slow or hasten the rate of progression of Parkinson disease? The results of the Elldopa trial. Neurology 2003;60(S1):A80.Google Scholar
Stocchi, F, Borgohain, R, Onofrj, M, et al. A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson’s disease patients. Mov Disord 2012;27:106–112.CrossRefGoogle ScholarPubMed
Schapira, AH, Stocchi, F, Borgohain, R, et al. Long-term efficacy and safety of safinamide as add-on therapy in early Parkinson’s disease. Eur J Neurol 2013;20:271–280.CrossRefGoogle ScholarPubMed
Calabresi, P, Kulisevsky, J. Safinamide as add-on therapy – moving beyond dopamine for a multifaceted approach in Parkinson’s disease. Eur Neurol Rev 2017;12(S5):2–6.Google Scholar
Cattaneo, C, Jost, WH, Bonizzoni, E. Long-term efficacy of safinamide on symptoms severity and quality of life in fluctuating Parkinson’s disease patients. J Parkinsons Dis 2020;10:89–97.CrossRefGoogle ScholarPubMed
Müller, T. Safinamide: an add-on treatment for managing Parkinson’s disease. Clin Pharmacol 2018;10:31–41.Google ScholarPubMed
Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol 1997;42:747–755.CrossRefGoogle 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;33:1528–1539.CrossRefGoogle ScholarPubMed
Rascol, O, Fabbri, M, Poewe, W. Amantadine in the treatment of Parkinson’s disease and other movement disorders. Lancet Neurol 2021;20:969–1056.CrossRefGoogle ScholarPubMed
Lee, TK, Yankee, EL. A review on Parkinson’s disease treatment. Neuroimmunol Neuroinflamm 2021;8:222–244.CrossRefGoogle Scholar
Saeedi, Y, Ghadimi, M, Rohani, M, et al. Impact of anticholinergic drugs withdrawal on motor function in patients with Parkinson’s disease. Clin Neurol Neurosurg 2021;202:106480.CrossRefGoogle ScholarPubMed
Berger, AA, Winnick, A, Welschmeyer, A, et al. Istradefylline to treat patients with Parkinson’s disease experiencing “off” episodes: a comprehensive review. Neurol Int 2020;12:109–129.CrossRefGoogle ScholarPubMed
Fox, S. Non-dopaminergic treatments for motor control in Parkinson’s disease. Drugs 2013;73:1405–1415.CrossRefGoogle ScholarPubMed
Jenner, P, Caccia, C. The role of glutamate in the healthy brain and in the pathophysiology of Parkinson’s disease. Eur Neurol Rev 2019;14(S2):2–12.Google Scholar
Thom, R, Silbersweig, DA, Boland, RJ. Major depressive disorder in medical illness: a review of assessment, prevalence, and treatment options. Psychosom Med 2019;81:246–255.CrossRefGoogle Scholar
Emre, M, Aarsland, D, Albanese, A, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 2004;351:2509–2518.CrossRefGoogle ScholarPubMed
Chen, JJ. Treatment of psychotic symptoms in patients with Parkinson disease. Ment Health Clin 2017;7:262–270.CrossRefGoogle ScholarPubMed
Armstrong, MJ, Okun, MS. Diagnosis and treatment of Parkinson disease: a review. JAMA 2020;323:548–560.CrossRefGoogle ScholarPubMed
Ruan, X, Lin, F, Wu, D, et al. Comparative efficacy and safety of dopamine agonists in advanced Parkinson’s disease with motor fluctuations: a systematic review and network meta-analysis of double-blind randomized controlled trials. Front Neurosci 2021;15:728083.CrossRefGoogle ScholarPubMed
Stocchi, F. Conventional treatment-related motor complications: their prevention and treatment. In: Wolters, ECh, Baumann, CR, eds. Parkinson Disease and Other Movement Disorders. Motor Behavioural Disorders and Behavioural Motor Disorders. Amsterdam: VU University Press; 2014: 255–270.Google Scholar

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