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Chapter 19 - Drug-Induced Non-Motor Symptoms in Parkinson’s Disease

Published online by Cambridge University Press:  05 March 2022

By
Camila Aquino
Edited by
Néstor Gálvez-Jiménez ,
Amos D. Korczyn  and
Ramón Lugo-Sanchez
Néstor Gálvez-Jiménez
Affiliation:
Florida International University
Amos D. Korczyn
Affiliation:
Tel-Aviv University
Ramón Lugo-Sanchez
Affiliation:
Cleveland Clinic
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Summary

People with Parkinson’s disease (PD) experience a variety of non-motor symptoms. Many of these non-motor symptoms can appear in the early phases, in still drug-naïve patients. Others tend to develop overtime, with prolonged disease duration and exposure to higher doses of dopaminergic therapy [1]. Often, non-motor symptoms fluctuate in response to levodopa similarly to the pattern observed in motor fluctuations [2]. Complex mechanisms underlie the development of PD non-motor symptoms, therefore, the term “drug-induced” used in this chapter does not mean to “blame” the therapy for such complications. Instead, as discussed along the chapter, in most cases, the antiparkinsonian therapy simply worsens or triggers specific non-motor symptoms because PD increases patients’ susceptibility [3].

Type
Chapter
Information
Non-motor Parkinson's Disease , pp. 212 - 223
Publisher: Cambridge University Press
Print publication year: 2022

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References

Titova, N, Chaudhuri, KR. Non-motor Parkinson disease: new concepts and personalised management. Med J Aust 2018; 208: 404–409.CrossRefGoogle ScholarPubMed
Fox, SH, Lang, AE. Motor and non-motor fluctuations. Handb Clin Neurol 2007; 84: 157–184.Google Scholar
Schaeffer, E, Berg, D. Dopaminergic therapies for non-motor symptoms in Parkinson’s disease. CNS Drugs 2017; 31: 551–570.Google Scholar
Chaudhuri, KR, Schapira, AHV. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009; 8: 464–474.Google Scholar
Strowd, LC, Lee, AD, Yosipovitch G. Livedo reticularis associated with rasagiline (azilect). J Drugs Dermatol 2012; 11: 764–765.Google Scholar
Fénelon, G, Alves, G. Epidemiology of psychosis in Parkinson’s disease. J Neurol Sci 2010; 289: 12–17.Google Scholar
Fénelon, G, Soulas, T, Zenasni, F, et al. The changing face of Parkinson’s disease-associated psychosis: a cross-sectional study based on the new NINDS-NIMH criteria. Mov Disord 2010; 25: 763–766.CrossRefGoogle ScholarPubMed
Goetz, CG, Fan, W, Leurgans, S, et al. The malignant course of “benign hallucinations” in Parkinson disease. Arch Neurol 2006; 63: 713–716.Google Scholar
Ffytche, DH, Creese, B, Politis, M, et al. The psychosis spectrum in Parkinson disease. Nat Rev Neurol 2017; 13: 81–95.Google Scholar
Lenka, A, Pagonabarraga, J, Pal, PK, et al. Minor hallucinations in Parkinson disease. Neurology 2019; 93: 259–266.Google Scholar
Fenelon, G, Mahieux, F, Huon, R, et al. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain 2000; 123: 733–745.CrossRefGoogle ScholarPubMed
Goetz, CG, Stebbins, GT, Ouyang, B. Visual plus nonvisual hallucinations in Parkinson’s disease: development and evolution over 10 years. Mov Disord 2011; 26: 2196–2200.CrossRefGoogle ScholarPubMed
Diederich, NJ, Fénelon, G, Stebbins, G, et al. Hallucinations in Parkinson disease. Nature Rev Neurol 2009; 5: 331–342.Google Scholar
Llebaria, G, Pagonabarraga, J, Martínez-Corral, M, et al. Neuropsychological correlates of mild to severe hallucinations in Parkinson’s disease. Mov Disord 2010; 25: 2785–2791.Google Scholar
Ravina, B, Marder, K, Fernandez, HH, et al. Diagnostic criteria for psychosis in Parkinson’s disease: report of an NINDS, NIMH work group. Mov Disord 2007; 22: 1061–1068.CrossRefGoogle ScholarPubMed
Fernandez, HH, Aarsland, D, Fénelon, G, et al. Scales to assess psychosis in Parkinson’s disease: critique and recommendations. Mov Disord 2008; 23: 484–500.Google Scholar
Cummings, JL, Mega, M, Gray, K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994; 44: 2308–2314.CrossRefGoogle ScholarPubMed
Kay, SR, Opler, LA, Lindenmayer, J-P. The Positive and Negative Syndrome Scale (PANSS): rationale and standardisation. Br J Psychiatry 1989; 155: 59–65.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: 2129–2170.CrossRefGoogle ScholarPubMed
Chaudhuri, KR, Martinez-Martin, P, Brown, RG, et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord 2007; 22: 1901–1911.Google Scholar
Voss, T, Bahr, D, Cummings, J, et al. Performance of a shortened Scale for Assessment of Positive Symptoms for Parkinson’s disease psychosis. Parkinsonism Relat Disord 2013; 19: 295–299.Google Scholar
Zhu, K, van Hilten, JJ, Putter, H, et al. Risk factors for hallucinations in Parkinson’s disease: results from a large prospective cohort study. Mov Disord 2013; 28: 755.Google Scholar
la Riva de, P, Smith, K, Xie, SX, et al. Course of psychiatric symptoms and global cognition in early Parkinson disease. Neurology 2014; 83: 1096–1103.Google Scholar
Forsaa, EB, Larsen, JP, Wentzel-Larsen, T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol 2010; 67: 996–1001.CrossRefGoogle ScholarPubMed
Morgante, L, Colosimo, C, Antonini, A, et al. Psychosis associated to Parkinson’s disease in the early stages: relevance of cognitive decline and depression. J Neurol Neurosurg Psychiatry 2011; 83: 76–82.Google Scholar
Mack, J, Rabins, P, Anderson, K, et al. Prevalence of psychotic symptoms in a community-based Parkinson disease sample. Am J Geriatr Psychiatry 2012; 20: 123–132.Google Scholar
Huot, P, Johnston, TH, Darr, T, et al. Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations. Mov Disord 2010; 25: 1399–1408.Google Scholar
Cho, SS, Strafella, AP, Duff-Canning, S, et al. The relationship between serotonin-2A receptor and cognitive functions in nondemented Parkinson’s disease patients with visual hallucinations. Mov Disord Clin Pract 2017; 4: 698–709.Google Scholar
Ballanger, B, Strafella, AP, van Eimeren, T, et al. Serotonin 2 A receptors and visual hallucinations in Parkinson disease. Arch Neurol 2010; 67: 416–421.Google Scholar
Janzen, J, t’ Ent, D, Lemstra, AW, et al. The pedunculopontine nucleus is related to visual hallucinations in Parkinson’s disease: preliminary results of a voxel-based morphometry study. J Neurol 2011; 259: 147–154.CrossRefGoogle ScholarPubMed
Wilby, KJ, Johnson, EG, Johnson, HE, et al. Evidence-based review of pharmacotherapy used for Parkinson’s disease psychosis. Ann Pharmacother 2017; 51: 682–695.Google Scholar
Fernandez, HH, Okun, MS, Rodriguez, RL, et al. Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study. Int J Neurosci 2009; 119: 2196–2205.CrossRefGoogle Scholar
Shotbolt, P, Samuel, M, Fox, C, et al. A randomized controlled trial of quetiapine for psychosis in Parkinson’s disease. Neuropsychiatr Dis Treat 2009; 5: 327–332.Google Scholar
Ondo, WG, Tintner, R, Voung, KD, et al. Double‐blind, placebo‐controlled, unforced titration parallel trial of quetiapine for dopaminergic‐induced hallucinations in Parkinson’s disease. Mov Disord 2005; 20: 958–963.Google Scholar
Rabey, JM, Prokhorov, T, Miniovitz, A, et al. Effect of quetiapine in psychotic Parkinson’s disease patients: a double‐blind labeled study of 3 months’ duration. Mov Disord 2007; 22: 313–318.CrossRefGoogle ScholarPubMed
Seppi, K, Ray Chaudhuri, K., Coelho, M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease – an evidence‐based medicine review. Mov Disord 2019; 34: 180–198.Google Scholar
Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl J Med 1999; 340: 757–763.Google Scholar
Pollak, P, Tison, F, Rascol, O, et al. Clozapine in drug-induced psychosis in Parkinson’s disease: a randomised, placebo-controlled study with open follow up. J Neurol Neurosurg Psychiatry 2004; 75: 689–695.CrossRefGoogle ScholarPubMed
Alvir, JMJ, Lieberman, JA, Safferman, AZ, et al. Clozapine-induced agranulocytosis – incidence and risk factors in the United States. N Eng J Med 2010; 329: 162–167.Google Scholar
Cummings, J, Isaacson, S, Mills, R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet 2014; 383: 533–540.Google Scholar
Meltzer, HY, Mills, R, Revell, S, et al. Pimavanserin, a serotonin2A receptor inverse agonist, for the treatment of Parkinson’s disease psychosis. Neuropsychopharmacol 2009; 35: 881–892.Google Scholar
The Lancet Neurology, . Difficult choices in treating Parkinson’s disease psychosis. Lancet Neurol 2018; 17: 569.Google Scholar
Verbaan, D, van Rooden, SM, Visser, M, et al. Nighttime sleep problems and daytime sleepiness in Parkinson’s disease. Mov Disord 2008; 23: 35–41.CrossRefGoogle ScholarPubMed
Knie, B, Mitra, MT, Logishetty, K, et al. Excessive daytime sleepiness in patients with Parkinson’s disease. CNS Drugs 2011; 25: 203–212.Google Scholar
Shpirer, I, Miniovitz, A, Klein, C, et al. Excessive daytime sleepiness in patients with Parkinson’s disease: a polysomnography study. Mov Disord 2006; 21: 1432–1438.CrossRefGoogle ScholarPubMed
Paus, S, Brecht, HM, Köster, J, et al. Sleep attacks, daytime sleepiness, and dopamine agonists in Parkinson’s disease. Mov Disord 2003; 18: 659–667.CrossRefGoogle ScholarPubMed
Gros, P, Videnovic, A. Overview of sleep and circadian rhythm disorders in Parkinson disease. Clin Geriatr Med 2020; 36: 119–130.Google Scholar
Chaudhuri, KR, Pal, S, Brefel-Courbon, C. ‘Sleep attacks’ or ‘unintended sleep episodes’ occur with dopamine agonists. Drug-Safety 2002; 25: 473–483.Google Scholar
Amara, AW, Chahine, LM, Caspell-Garcia, C, et al. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease. J Neurol Neurosurg Psychiatry 2017; 88: 653–662.CrossRefGoogle ScholarPubMed
Razmy, A, Lang, AE, Shapiro, CM. Predictors of impaired daytime sleep and wakefulness in patients with Parkinson disease treated with older (ergot) vs newer (nonergot) dopamine agonists. Arch Neurol 2004; 61: 97–102.Google Scholar
Silkis, IG. Search for approaches to correction of daytime sleepiness induced by dopaminergic drugs during treatment of Parkinson’s disease: neurochemical aspects. Neurochem J 2009; 3: 221–231.CrossRefGoogle Scholar
Chaudhuri, KR, Martin, PM, Schapira, AHV, et al. International multicenter pilot study of the first comprehensive self‐completed nonmotor symptoms questionnaire for Parkinson’s disease: The NMSQuest study. Mov Disord 2006; 21: 916–923.Google Scholar
Pfeiffer, RF. Non-motor symptoms in Parkinson’s disease. Parkinsonism Relat Disord 2016; 22: S119–122.Google Scholar
Pfeiffer, RF. Gastrointestinal dysfunction in Parkinson’s disease. Parkinsonism Relat Disord 2011; 17: 10–15.Google Scholar
Wood, LD. Clinical review and treatment of select adverse effects of dopamine receptor agonists in Parkinson’s disease. Drugs Aging 2010; 27: 295–310.Google Scholar
Schapira, AHV, Chaudhuri, KR, Jenner, P. Non-motor features of Parkinson disease. Nat Rev Neurosci 2017; 18: 435–450.Google Scholar
Seppi, K, Ray Chaudhuri, K., Coelho, M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease – an evidence‐based medicine review. Mov Disord 2019; 34: 180–198.CrossRefGoogle ScholarPubMed
Quarracino, C, Otero-Losada, M, Capani, F, et al. State-of-the-art pharmacotherapy for autonomic dysfunction in Parkinson’s disease. Expert Opin Pharmacother 2020; 21: 445–457.Google Scholar
Chou, KL. Adverse events from the treatment of Parkinson’s disease. Neurol Clin 2008; 26: 65–83.Google Scholar
Witjas, T, Kaphan, E, Azulay, JP, et al. Nonmotor fluctuations in Parkinson’s disease frequent and disabling. Neurology 2002; 59: 408–413.Google Scholar
Kummer, A, Scalzo, P, Cardoso, F, et al. Evaluation of fatigue in Parkinson’s disease using the Brazilian version of Parkinson’s Fatigue Scale. Acta Neurol Scand 2011; 123: 130–136.Google Scholar
Todorova, A, Jenner, P, Ray Chaudhuri, K. Non-motor Parkinson’s: integral to motor Parkinson’s, yet often neglected. Prac Neurol 2014; 14(5): 310.Google Scholar
Aquino, CC, Fox, SH. Clinical spectrum of levodopa-induced complications. Mov Disord 2015; 30: 80–89.Google Scholar
Aquino, CC, Mestre, T, Lang, AE. Restless genital syndrome in Parkinson disease. JAMA Neurol 2014; 71: 1559–1561.Google Scholar
Classen, J, Koschel, J, Oehlwein, C, et al. Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues. J Neural Transm 2017; 124: 1029–1036.Google Scholar
Kleiner-Fisman, G, Martine, R, Lang, AE, et al. Development of a non-motor fluctuation assessment instrument for Parkinson disease. Parkinsons Dis 2011; 2011: 1–13. DOI:10.4061/2011/292719CrossRefGoogle ScholarPubMed
Fernández, RM, Schmitt, E, Martin, PM, et al. The hidden sister of motor fluctuations in Parkinson’s disease: a review on nonmotor fluctuations. Mov Disord 2016; 31: 1080–1094.Google Scholar

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