Hostname: page-component-8448b6f56d-qsmjn Total loading time: 0 Render date: 2024-04-19T16:48:55.291Z Has data issue: false hasContentIssue false
  • English
  • Français

Course, Prognosis, and Management of Psychosis in Parkinson's Disease: Are Current Treatments Really Effective?

Published online by Cambridge University Press:  07 November 2014

Laura B. Zahodne  and
Hubert H. Fernandez
Get access Rights & Permissions [Opens in a new window]

Abstract

It is essential to recognize and treat psychosis in Parkinson's disease for several reasons. Studies have shown that psychosis in Parkinson's disease patients is a strong risk factor for nursing home placement. Psychosis may be the greatest source of stress for caretakers of Parkinson's patients; it is often persistent, and its presence markedly increases mortality. Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient's antiparkinsonian medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic is presently the treatment of choice. An emerging treatment option is acetylcholinesterase inhibitors. This article reviews what is currently known about the course, prognosis, and treatment strategies in Parkinson's disease psychosis.

Type
Supplement
Information
CNS Spectrums , Volume 13 , Issue S4: Neuropsychiatric Aspects of Parkinson's Disease: Focus on Insomnia, Daytime Sleepiness, and Psychosis , March 2008 , pp. 26 - 33
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Goetz, CG, Vogel, C, Tanner, CM, Stebbins, GT. Early dopaminergic drug-induced hallucinations in parkinsonian patients. Neurology. 1998;51(3):811–814.CrossRefGoogle ScholarPubMed
2.Ramirez-Ruiz, B, Junque, C, Marti, MJ, Valldeoriola, F, Tolosa, E. Cognitive changes in Parkinson's disease patients with visual hallucinations. Dement Geriatr Cogn Disord. 2007;23(5):281–288.CrossRefGoogle ScholarPubMed
3.Uc, EY, Struck, LK, Rodnitzky, RL, Zimmerman, B, Dobson, J, Evans, WJ. Predictors of weight loss in Parkinson's disease. Mov Disor. 2006;21(7):930–936.CrossRefGoogle ScholarPubMed
4.Aarsland, D, Larsen, JP, Karlsen, K, Lim, NG, Tandberg, E. Mental symptoms in Parkinson's disease are important contributors to caregiver distress. Int J Geriat Psychiatry. 1999;14(10):866–874.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
5.Aarsland, D, Larsen, JP, Tandbert, E. Predictors of nursing home placement in PD: a population-based prospective study. J Am Geriatr Soc. 2000;48:938–942.CrossRefGoogle Scholar
6.Goetz, CG, Stebbins, GT. Risk factors for nursing home placement in advanced Parkinson's disease. Neurology. 1993;43(11):2227–2229CrossRefGoogle ScholarPubMed
7.Sanchez-Ramos, JR, Ortoll, R, Paulson, GW. Visual hallucinations associated with Parkinson's disease. Arch Neurol. 1996;53(12):1265–1268.CrossRefGoogle Scholar
8.Juncos, JL, Jewart, RD, Neparizde, N, Hanfelt, J. Long-term prognosis of hallucinating Parkinson's disease patients treated with quetiapine or clozapine [abstract]. Neurology. 2002;58:435.Google Scholar
9.Factor, SA, Feustel, PJ, Friedman, JH, et al.Longitudinal outcome of Parkinson's disease patients with psychosis. Neurology. 2003;60(11):1756–1761.CrossRefGoogle ScholarPubMed
10.Ramirez-Ruiz, B, Junque, C, Marti, MJ, Valldeoriola, F, Tolosa, E. Cognitive changes in Parkinson's disease patients with visual hallucinations. Dement Geriatr Cogn Disord. 2007;23(5):281–288.CrossRefGoogle ScholarPubMed
11.Aarsland, D, Larsen, JP, Karlsen, K, Lim, NG, Tandberg, E. Mental symptoms in Parkinson's disease are important contributors to caregiver distress. Int J Geriat Psychiatry. 1999;14(10):866–874.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
12.Goetz, CG, Stebbins, GT. Risk factors for nursing home placement in advanced Parkinson's disease. Neurology. 1993;43(11):2227–2229.CrossRefGoogle ScholarPubMed
13.Goetz, CG, Stebbins, GT. Mortality and hallucinations in nursing home patients with advanced Parkinson's disease. Neurology. 1995;45(4):669–671.CrossRefGoogle ScholarPubMed
14.Fernandez, HH, Donnelly, EM, Friedman, JH. Long-term outcome of clozapine use for psychosis in parkinsonian patients. Mov Disord. 2004;19(7):831–833.CrossRefGoogle ScholarPubMed
15.Factor, SA, Feustel, PJ, Friedman, JH, et al.Longitudinal outcome of Parkinson's disease patients with psychosis. Neurology. 2003;60(11):1756–1761.CrossRefGoogle ScholarPubMed
16.Papapetropoulos, S. Drug-induced psychosis in Parkinson disease: phenomenology and correlations among psychosis rating instruments. Clin Neuropharmacol. 2006;29(1):59.CrossRefGoogle ScholarPubMed
17.Wolters, EC, Berendse, HW. Management of psychosis in Parkinson's disease. Curr Opin Neurol. 2001;14:499–504.CrossRefGoogle ScholarPubMed
18.Goetz, CG, Fan, W, Leurgans, S, Bernard, B, Stebbins, GT. The malignant course of “bsnign hallucinations” in Parkinson disease. Arch Neurol. 2006;63(5):713–716.CrossRefGoogle Scholar
19.Moskovitz, C, Moses, H, Klawans, HL. Levodopa-induced psychosis: a kindling phenomenon. Am J Psychiatry. 1978;135(6):669–675.Google ScholarPubMed
20.Pappert, EJ, Goetz, CG, Niederman, FG, Raman, R, Leurgans, S. Sleep fragmentation, and altered dream phenomena in PD. Mov Disord. 1999;14(1):117–121.3.0.CO;2-0>CrossRefGoogle Scholar
21.Goetz, CG, Wuu, J, Curgian, LM, Leurgans, S. Hallucinations and sleep disorders in PD: Six-year prospective longitudinal study. Neurology. 2005;64(1):81–86.CrossRefGoogle ScholarPubMed
22.Goetz, CG, Leurgans, S, Pappert, EJ, Raman, R, Stemer, AB. Prospective longitudinal assess-ment of hallucinations in Parkinson's disease. Neurology. 2001;57(11):2078–2082.CrossRefGoogle Scholar
23.Factor, SA, Feustel, PJ, Friedman, JH, et al.Longitudinal outcome of Parkinson's disease patients with psychosis. Neurology. 2003;60(11):1756–1761.CrossRefGoogle ScholarPubMed
24.Goetz, CG, Leurgans, S, Pappert, EJ, Raman, R, Stemer, AB. Prospective longitudinal assess-ment of hallucinations in Parkinson's disease. Neurology. 2001;57(11):2078–2082.CrossRefGoogle Scholar
25.Fernandez, HH, Donnelly, EM, Friedman, JH. Long-term outcome of clozapine use for psychosis in parkinsonian patients. Mov Disord. 2004;19(7):831–833.CrossRefGoogle ScholarPubMed
26.Fernandez, HH, Trieschmann, ME, Okun, MS. Rebound psychosis: effect of discontinuation of antipsychotics in Parkinson's disease. Mov Disord. 2005;20(1):104–115CrossRefGoogle ScholarPubMed
27.Fernandez, HH, Friedman, JF. The role of atypical antipsychotics in the treatment of movement disorders. CNS Drugs. 1999;11(6):467–483.CrossRefGoogle Scholar
28.Friedman, JH, Fernandez, HH. The non-motor problems of Parkinson's disease. Neurology. 2000;6:18–27.Google Scholar
29.Henderson, MJ, Mellers, JDC. Psychosis in Parkinson's disease: “between a rock and a hard place.” Int Rev Psychiatry. 2000;12:319–334.CrossRefGoogle Scholar
30.Frieling, H, Hillemacher, T, Ziegenbein, M, Neundorfer, B, Bleich, S. Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis. Eur Neuropsychopharmacol. 2007;17(3):165–171.CrossRefGoogle ScholarPubMed
31.Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease. N Engl J Med. 1999;340(10):757–763.CrossRefGoogle Scholar
32.Friedman, JH, Factor, SA. Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. Mov Disord. 2000;151(2):201–211.3.0.CO;2-D>CrossRefGoogle Scholar
33.Pollak, P, Tison, F, Rascol, O, et al.Clozapine in drug induced psychosis in Parkinson's disease: a randomized, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry. 2004;75(5):689–695.CrossRefGoogle ScholarPubMed
34.Fernandez, HH, Friedman, JH, Lansang, MC, Factor, SA, Molho, ES, Coskun, DJ. Diabetes mellitus among parkinsonian patients treated chronically with clozapine. Parkinsonism Relat Disord. 2004;10(7):439–441.CrossRefGoogle ScholarPubMed
35.Klein, C, Gordon, J, Pollak, L, Rabey, JM. Clozapine in Parkinson's disease psychosis: 5-year follow-up review. Clin Neuropharmacol. 2003;26(1):8–11.CrossRefGoogle ScholarPubMed
36.Honigfeld, G, Arellano, F, Sethi, J, Bianchini, A, Schein, J. Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry. J Clin Psychiatry. 1998;59(Suppl 3):3–7.Google ScholarPubMed
37.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(5):689–695.CrossRefGoogle ScholarPubMed
38.Grant, S, Fitton, A. Risperidone: a review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs. 1994;43(2):253–573.CrossRefGoogle Scholar
39.Rustembegovic, A, Sofic, E, Wichart, I. Serum prolactin, leptin, lipids and lipoprotein levels during antipsychotic treatment in Parkinson's disease and related psychosis. Med Arh. 2006;60(4):211–212.Google ScholarPubMed
40.Workman, RH Jr, Orengo, CA, Bakey, AA, Molinari, VA, Kunik, ME. The use of risperidone for psychosis and agitation in demented patients with Parkinson's disease. J Neuropsychiatry Clin Neurosci. 1997;9(4)594–597.Google ScholarPubMed
41.Meco, G, Alessandri, A, Giustini, P, Bonifati, V. Risperidone in levodopa-induced psychosis in advanced Parkinson's disease: an open-label, long-term study. Mov Disord. 1997;12(4):610–612.CrossRefGoogle ScholarPubMed
42.Leopold, NA. Risperidone treatment of drug-related psychosis in patients with parkinsonism. Mov Disord. 2000;15(2):301–304.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
43.Mohr, E, Mendis, T, Hildebrand, K, De Deyn, PP. Risperidone in the treatment of dopamine-induced psychosis in Parkinson's disease: an open pilot trial. Mov Disord. 2000;15(6):1230–1237.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
44.Factor, SA, Molho, ES, Friedman, JH. Risperidone and Parkinson's disease [letter]. Mov Disord. 2001;12:364–369.Google Scholar
45.Ellis, T, Cudkowicz, ME, Sexton, PM, Growdon, JH. Clozapine and risperidone treatment of psychosis in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2000;12(3):364–369.CrossRefGoogle ScholarPubMed
46.Moore, NA, Tye, NC, Axton, MS, Risius, FC. The behavioral pharmacology of olanzapine, a novel “atypical” antipsychotic agent. J Pharmacol Exp Ther. 1992;262(2):545–551.Google ScholarPubMed
47.Wolters, EC, Jansen, EN, Tuynman-Qua, HG, Bergmans, PL. Olanzapine in the treatment of dopaminomimetic psychosis in patients with Parkinson's disease. Neurology. 1996;47(4):1085–1087.CrossRefGoogle ScholarPubMed
48.Breier, A, Sutton, VK, Feldman, PD, et al.Olanzapine in the treatment of dopamimetic-induced psychosis in patients with Parkinson's disease. Biol Psychiatry. 2002;52(5):438–445.CrossRefGoogle ScholarPubMed
49.Ondo, WG, Levy, JK, Vuong, KD, Hunter, C, Jankovic, J. Olanzapine treatment for dopaminergic-induced hallucinations. Mov Disord. 2002;17(5):1031–1035.CrossRefGoogle ScholarPubMed
50.Goetz, CG, Blasucci, LM, Leurgans, S, Pappert, EJ. Olanzapine and clozapine: comparative effects on motor function in hallucinating PD patients. Neurology. 2000;55(6):789–794.CrossRefGoogle ScholarPubMed
51.Fernandez, HH, Trieschmann, ME, Friedman, JH. Treatment of psychosis in Parkinson's disease: safety considerations. Drug Saf. 2003;26(9):643–659.CrossRefGoogle ScholarPubMed
52.Reddy, S, Factor, SA, Molho, ES, Feustel, PJ. The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia. Mov Disord. 2002;17(4):676–681.CrossRefGoogle ScholarPubMed
53.Fernandez, HH, Trieschmann, ME, Burke, MA, Friedman, JH. Long-term outcome of quetiapine use for psychosis among Parkinsonian patients. Mov Disord. 2003;18(5):510–514.CrossRefGoogle ScholarPubMed
54.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):958–963.CrossRefGoogle ScholarPubMed
55.Rabey, JM, Prokhorov, T, Miniovich, A, Klein, C. The effect of quetiapine in Parkinson's disease (PD) psychotic patients: A double-blind labeled study of three months duration. Mov Disord. 2005;20(suppl 10):46.Google Scholar
56.Morgante, L, Epifanio, A, Spina, E, et al.Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis. Clin Neuropharmacol. 2004;27(4):153–156.CrossRefGoogle ScholarPubMed
57.Glassman, AH. Schizophrenia, antipsychotic drugs, and cardiovascular disease. J Clin Psychiatry. 2005;66(suppl 6):5–10.Google ScholarPubMed
58.Connemann, BJ, Schonfeldt-Lecuona, C. Ziprasidone in Parkinson's disease psychosis. Can J Psychiatry. 2004;49(1):73.CrossRefGoogle ScholarPubMed
59.Shiah, IS, Lin, CL, Mao, WC, Luu, SU. Ziprasidone in the treatment of Parkinson's disease psychosis. Eur Psychiatry. 2006;21(8):578–579.CrossRefGoogle ScholarPubMed
60.Gomez-Esteban, JC, Zarranz, JJ, Velasco, F, et al.Use of ziprasidone in parkinsonian patients with psychosis. Clin Neuropharmacol. 2005;28(3):111–114.CrossRefGoogle ScholarPubMed
61.Oechsner, M, Korchounov, A. Parenteral ziprasidone: a new atypical neuroleptic for emergency treatment of psychosis in Parkinson's disease? Hum Psychopharmacol. 2005;20(3):203–205.CrossRefGoogle ScholarPubMed
62.Weiden, PJ, Iqbal, N, Mendelowitz, AJ, Tandon, R, Zimbroff, DL, Ross, R. Best clinical practice with ziprasidone: update after one year of experience. J Psychiatr Pract. 2002;8(2):81–97.CrossRefGoogle ScholarPubMed
63.McGavin, JK, Goa, KL. Aripiprazole. CNS Drugs. 2002;16(11):779–786.CrossRefGoogle ScholarPubMed
64.Schonfeldt-Lecuona, C, Connemann, BJ. Aripiprazole and Parkinson's disease psychosis. Am J Psychiatry. 2004;161(2):373–374.CrossRefGoogle ScholarPubMed
65.Wickremaratchi, M, Morris, HR. Aripiprazole associated with severe exacerbation of Parkinson's disease. Mov Disord. 2006;21(9):1538–1589.CrossRefGoogle ScholarPubMed
66.Lopez-Meza, E, Ruiz-Chow, A, Ramirez-Bermudez, J. Aripiprazole in psychosis associated with Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2005;17(3):421–422.CrossRefGoogle ScholarPubMed
67.Fernandez, HH, Trieschmann, ME, Friedman, JH. Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol. 2004;27(1):4–5.CrossRefGoogle ScholarPubMed
68.Friedman, JH, Berman, RM, Goetz, CG, et al.Open-label flexible-dose pilot study to evaluate the safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson's disease. Mov Disord. 2006;21(12):2078–2081.CrossRefGoogle ScholarPubMed
69.Schneider, LS, Dagerman, KS, Insel, P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294(15):1934–1943.CrossRefGoogle ScholarPubMed
70.Ott, B, Lannon, M. Exacerbation of parkinsonism by tacrine. Clin Neuropharmacol. 1992;15(4):322–325.CrossRefGoogle ScholarPubMed
71.Hutchinson, M, Fazzini, E. Cholinesterase inhibition in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1996;61(3):324–325.CrossRefGoogle ScholarPubMed
72.Fabbrini, G, Barbanti, P, Aurilia, C, Pauletti, C, Lenzi, GL, Meco, G. Donepezil in the treatment of hallucinations and delusions in Parkinson's disease. Neurol Sci. 2002;23(1):41–43.CrossRefGoogle ScholarPubMed
73.Bergman, J, Lerner, V. Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease. Clin Neuropharmacol. 2002;25(2):107–110.CrossRefGoogle ScholarPubMed
74.Kurita, A, Ochiai, Y, Kono, Y, Suzuki, M, Inoue, K. The beneficial effect of donepezil on visual hallucinations in three patients with Parkinson's disease. J Geriatr Psychiatry Neurol. 2003;16(3):184–188.CrossRefGoogle ScholarPubMed
75.Aarsland, D, Laake, K, Larsen, J, Janvin, C. Donepezil for cognitive impairment in Parkinson's disease: a randomized controlled study. J Neurol Neurosurg Psychiatry. 2002;72(6):708–712.CrossRefGoogle Scholar
76.Ravina, B, Putt, M, Siderowf, A, et al.Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry. 2005;76(7):934–939.CrossRefGoogle ScholarPubMed
77.Aarsland, D, Hutchinson, M, Larsen, JP. Cognitive, psychiatrie and motor response to galantamine in Parkinson's disease with dementia. Int J Geriatr Psychiatry. 2003;18(10):937–941.CrossRefGoogle ScholarPubMed
78.Reading, PJ, Luce, AK, McKeith, IG. Rivastigmine in the treatment of parkinsonian psychosis and cognitive impairment: preliminary findings from an open trial. Mov Disord. 2001;16(6):1171–1174.CrossRefGoogle ScholarPubMed
79.Burn, D, Emre, M, McKeith, I, et al.Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease. Mov Disord. 2006;21(11):1899–1907.CrossRefGoogle ScholarPubMed
80.Lipton, SA. The molecular basis of memantine action in Alzheimer's disease and other neurologie disorders: low affinity, uncompetitive antagonism. Curr Alzheimer Res. 2005;2(2):155–165.CrossRefGoogle Scholar
81.Lipton, SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006;5(2):160–170.CrossRefGoogle ScholarPubMed
82.Winblad, B, Jones, RW, Wirth, Y, Stoffler, A, Mobius, HJ. Memantine in moderate to severe Alzheimer's disease: a meta-analysis of randomized clinical trials. Dement Geriatr Cogn Disord. 2007;24(1):20–27.CrossRefGoogle Scholar
83.Gauthier, S, Wirth, Y, Mobius, HJ. Effects of memantine on behavioural symptoms in Alzheimer's disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomized controlled studies. Int J Geriatr Psychiatry. 2005;20(5):459–464.CrossRefGoogle Scholar
84.Cummings, JL, Schneider, E, Tariot, PN, Graham, SM and the Memantine MEM-MD-02 Study Group. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology. 2006;67(1):57–63.CrossRefGoogle ScholarPubMed
85.Sleeper, RB. Antipsychotic dose-sparing effect with addition of memantine. Ann Pharmacother. 2005;39(9):1573–1576.CrossRefGoogle ScholarPubMed
86.Ridha, BH, Josephs, KA, Rossor, MN. Delusions and hallucinations in dementia with Lewy bodies: worsening with memantine. Neurology. 2005;65(3):481–482.CrossRefGoogle ScholarPubMed
87.Monastero, R, Camarda, C, Pipia, C, Camarda, R. Visual hallucinations and agitation in Alzheimer's disease due to memantine: report of three cases. J Neurol Neurosurg Psychiatry. 2007;78(5):546.CrossRefGoogle ScholarPubMed
88.Zoldan, J, Friedberg, G, Goldberg-Stern, H, Melamed, E. Ondansetron for hallucinosis in advanced Parkinson's disease. Lancet. 1993;341(8844):562–563.CrossRefGoogle ScholarPubMed
89.Zoldan, J, Friedberg, G, Livneh, M, Melamed, E. Psychosis in advanced Parkinson's disease: treatment with ondansetron, a 5-HT3 receptor antagonist. Neurology. 1995;45(7):1305–1308.CrossRefGoogle Scholar
90.Eichhorn, TE, Brunt, E, Oertel, WH. Ondansetron treatment of L-dopa-induced psychosis. Neurology. 1996;47(6):1608–1609.CrossRefGoogle ScholarPubMed
91.Goetz, CG, Tanner, CM, Klawans, HL. Pharmacology of hallucinations induced by long-term drug therapy. Am J Psychiatry. 1982;139(4):494–497.Google ScholarPubMed
92.Schapira, AH, Bezard, E, Brotchie, J, et al.Novel pharmacological targets for the treatment of Parkinson's disease. Nat Rev Drug Discov. 2006;5(10):845–854.CrossRefGoogle ScholarPubMed
93.Foltynie, T, Brayne, C, Barker, RA. The heterogeneity of idiopathic Parkinson's disease. J Neurol. 2002;249(2):138–145.CrossRefGoogle ScholarPubMed
94.Witjas, T, Kaphan, E, Azulay, JP, et al.Nonmotor fluctuations in Parkinson's disease: frequent and disabling. Neurology. 2002;59(3):408–413.CrossRefGoogle ScholarPubMed
95.Global Parkinson's Disease Survey Steering Committee. Factors impacting on quality of life in Parkinson's disease: results from an international survey. Mov Disord 2002;17:60–67.CrossRefGoogle Scholar
96.Hely, MA, Morris, JG, Reid, WG, Trafficante, R. Sydney multicenter study of Parkinson's disease: non-l-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20(2):190–199.CrossRefGoogle Scholar
97.Chaudhuri, KR, Healy, DG, Schapira, AH, National Institute for Clinical Excellence. Nonmotor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006;5(3):235–245.CrossRefGoogle ScholarPubMed
98.Schapira, AH, Bezard, E, Brotchie, J, et al.Novel pharmacological targets for the treatment of Parkinson's disease. Nat Rev Drug Discov. 2006;5(10):845–854.CrossRefGoogle ScholarPubMed