The American Journal of Medicine
Volume 122, Issue 7 , Pages 614-622 , July 2009

Pharmacological Management of Psychosis in Elderly Patients with Parkinsonism

  • Mehrul Hasnain, MD

      Affiliations

    • Department of Psychiatry, Western Regional Integrated Health Authority, Sir Thomas Roddick Hospital, Stephenville, Newfoundland, Canada
    • Corresponding Author InformationRequests for reprints should be addressed to Mehrul Hasnain, MD, Sir Thomas Roddick Hospital, 142 Minnesota Drive, Stephenville, Newfoundland A2N 2V6, Canada
    • ,
  • W. Victor R. Vieweg, MD

      Affiliations

    • Department of Psychiatry, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va
    • Department of Medicine Services, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va
    • Department of Psychiatry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond
    • Department of Internal Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond
    • ,
  • Mark S. Baron, MD

      Affiliations

    • Department of Neurology, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va
    • Department of Neurology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond
    • ,
  • Mary Beatty-Brooks, MA

      Affiliations

    • Department of Medical Media, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va
    • ,
  • Antony Fernandez, MD

      Affiliations

    • Department of Psychiatry, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Va
    • Department of Psychiatry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond
    • ,
  • Anand K. Pandurangi, MD

      Affiliations

    • Department of Psychiatry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond

References 

  1. Bennett DA, Beckett LA, Murray AM, et al. Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med. 1996;334:71–76
  2. Friedman JH, Skeete R, Fernandez HH. Unrecognized parkinsonism in acute care medical patients receiving neurological consultations. J Gerontol A Biol Sci Med Sci. 2003;58:94–95
  3. Friedman JH, Fernandez HH, Trieschmann MM. Parkinsonism in a nursing home: underrecognition. J Geriatr Psychiatry Neurol. 2004;17:39–41
  4. Weintraub D, Hurtig HI. Presentation and management of psychosis in Parkinson's disease and dementia with Lewy bodies. Am J Psychiatry. 2007;164:1491–1498
  5. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65:1863–1872
  6. Savitt JM, Dawson VL, Dawson TM. Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest. 2006;116:1744–1754
  7. de Rijk MC, Breteler MM, Graveland GA, et al. Prevalence of Parkinson's disease in the elderly: the Rotterdam Study. Neurology. 1995;45:2143–2146
  8. Morens DM, Davis JW, Grandinetti A, et al. Epidemiologic observations on Parkinson's disease: incidence and mortality in a prospective study of middle-aged men. Neurology. 1996;46:1044–1050
  9. Aarsland D, Bronnick K, Ehrt U, et al. Neuropsychiatric symptoms in patients with Parkinson's disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatry. 2007;78:36–42
  10. Factor SA, Feustel PJ, Friedman JH, et al. Longitudinal outcome of Parkinson's disease patients with psychosis. Neurology. 2003;60:1756–1761
  11. Aarsland D, Andersen K, Larsen JP, et al. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003;60:387–392
  12. Zaccai J, McCracken C, Brayne C. A systematic review of prevalence and incidence studies of dementia with Lewy bodies. Age Ageing. 2005;34:561–566
  13. Kosaka K. Diffuse Lewy body disease in Japan. J Neurol. 1990;237:197–204
  14. Nussbaum RL, Ellis CE. Alzheimer's disease and Parkinson's disease. N Engl J Med. 2003;348:1356–1364
  15. Mitchell SL. Extrapyramidal features in Alzheimer's disease. Age Ageing. 1999;28:401–409
  16. Ropacki SA, Jeste DV. Epidemiology of and risk factors for psychosis of Alzheimer's disease: a review of 55 studies published from 1990 to 2003. Am J Psychiatry. 2005;162:2022–2030
  17. Stern Y, Albert M, Brandt J, et al. Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: prospective analyses from the Predictors Study. Neurology. 1994;44:2300–2307
  18. Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain (II. Patterns of loss of dopamine-containing neurons in Parkinson's disease). Brain. 1999;122(Pt 8):1437–1448
  19. Obeso JA, Rodriguez-Oroz MC, Rodriguez M, et al. The basal ganglia and disorders of movement: pathophysiological mechanisms. News Physiol Sci. 2002;17:51–55
  20. Kuzuhara S, Yoshimura M. Clinical and neuropathological aspects of diffuse Lewy body disease in the elderly. Adv Neurol. 1993;60:464–469
  21. Camicioli R, Kaye J, Payami H, et al. Apolipoprotein E epsilon4 is associated with neuronal loss in the substantia nigra in Alzheimer's disease. Dement Geriatr Cogn Disord. 1999;10:437–441
  22. Brown FW. The neurobiology of late-life psychosis. Crit Rev Neurobiol. 1993;7:275–289
  23. Keshavan MS, Berger G, Zipursky RB, et al. Neurobiology of early psychosis. Br J Psychiatry Suppl. 2005;48:s8–s18
  24. Miyamoto S, LaMantia AS, Duncan GE, et al. Recent advances in the neurobiology of schizophrenia. Mol Interv. 2003;3:27–39
  25. Meeks TW, Ropacki SA, Jeste DV. The neurobiology of neuropsychiatric syndromes in dementia. Curr Opin Psychiatry. 2006;19:581–586
  26. Perry EK, Marshall E, Kerwin J, et al. Evidence of a monoaminergic-cholinergic imbalance related to visual hallucinations in Lewy body dementia. J Neurochem. 1990;55:1454–1456
  27. Rochon PA, Stukel TA, Sykora K, et al. Atypical antipsychotics and parkinsonism. Arch Intern Med. 2005;165:1882–1888
  28. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55:181–184
  29. Rajput AH, Rozdilsky B, Rajput A. Accuracy of clinical diagnosis in parkinsonism—a prospective study. Can J Neurol Sci. 1991;18:275–278
  30. Wijkstra J, Lijmer J, Balk F, et al. Pharmacological treatment for psychotic depression. Cochrane Database Syst Rev. 2005;CD004044
  31. Young J, Inouye SK. Delirium in older people. BMJ. 2007;334:842–846
  32. Turjanski N, Lloyd GG. Psychiatric side-effects of medications: recent developments. Adv Psychiatr Treatment. 2005;11:58–70
  33. Kuzuhara S. Drug-induced psychotic symptoms in Parkinson's disease (Problems, management and dilemma). J Neurol. 2001;248(Suppl 3):III28–III31
  34. Ellis T, Cudkowicz ME, Sexton PM, Growdon JH. Clozapine and risperidone treatment of psychosis in Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2000;12:364–369
  35. Frieling H, Hillemacher T, Ziegenbein M, et al. Treating dopamimetic psychosis in Parkinson's disease: structured review and meta-analysis. Eur Neuropsychopharmacol. 2007;17:165–171
  36. Goetz CG, Blasucci LM, Leurgans S, Pappert EJ. Olanzapine and clozapine: comparative effects on motor function in hallucinating PD patients. Neurology. 2000;55:789–794
  37. The 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
  38. 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
  39. Fernandez HH, Donnelly EM, Friedman JH. Long-term outcome of clozapine use for psychosis in parkinsonian patients. Mov Disord. 2004;19:831–833
  40. Klein C, Gordon J, Pollak L, Rabey JM. Clozapine in Parkinson's disease psychosis: 5-year follow-up review. Clin Neuropharmacol. 2003;26:8–11
  41. Burke WJ, Pfeiffer RF, McComb RD. Neuroleptic sensitivity to clozapine in dementia with Lewy bodies. J Neuropsychiatry Clin Neurosci. 1998;10:227–229
  42. Fernandez HH, Trieschmann ME, Friedman JH. Treatment of psychosis in Parkinson's disease: safety considerations. Drug Saf. 2003;26:643–659
  43. Rich SS, Friedman JH, Ott BR. Risperidone versus clozapine in the treatment of psychosis in six patients with Parkinson's disease and other akinetic-rigid syndromes. J Clin Psychiatry. 1995;56:556–559
  44. Leopold NA. Risperidone treatment of drug-related psychosis in patients with parkinsonism. Mov Disord. 2000;15:301–304
  45. Ondo WG, Levy JK, Vuong KD, et al. Olanzapine treatment for dopaminergic-induced hallucinations. Mov Disord. 2002;17:1031–1035
  46. Miyasaki JM, Shannon K, Voon V, et al. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66:996–1002
  47. Walker Z, Grace J, Overshot R, et al. Olanzapine in dementia with Lewy bodies: a clinical study. Int J Geriatr Psychiatry. 1999;14:459–466
  48. Cummings JL, Street J, Masterman D, Clark WS. Efficacy of olanzapine in the treatment of psychosis in dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2002;13:67–73
  49. Friedman JH, Factor SA. Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. Mov Disord. 2000;15:201–211
  50. Friedman JH, Fernandez HH. Atypical antipsychotics in Parkinson-sensitive populations. J Geriatr Psychiatry Neurol. 2002;15:156–170
  51. Merims D, Balas M, Peretz C, et al. Rater-blinded, prospective comparison: quetiapine versus clozapine for Parkinson's disease psychosis. Clin Neuropharmacol. 2006;29:331–337
  52. 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
  53. Prohorov T, Klein C, Miniovitz A, et al. The effect of quetiapine in psychotic parkinsonian patients with and without dementia (An open-labeled study utilizing a structured interview). J Neurol. 2006;253:171–175
  54. 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
  55. Fernandez HH, Trieschmann ME, Burke MA, et al. Long-term outcome of quetiapine use for psychosis among parkinsonian patients. Mov Disord. 2003;18:510–514
  56. Klein C, Prokhorov T, Miniovich A, et al. Long-term follow-up (24 months) of quetiapine treatment in drug-induced Parkinson disease psychosis. Clin Neuropharmacol. 2006;29:215–219
  57. Fernandez HH, Trieschmann ME, Burke MA, Friedman JH. Quetiapine for psychosis in Parkinson's disease versus dementia with Lewy bodies. J Clin Psychiatry. 2002;63:513–515
  58. Takahashi H, Yoshida K, Sugita T, et al. Quetiapine treatment of psychotic symptoms and aggressive behavior in patients with dementia with Lewy bodies: a case series. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:549–553
  59. Fernandez HH, Trieschmann ME, Friedman JH. Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol. 2004;27:4–5
  60. 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;21:2078–2081
  61. Lopez-Meza E, Ruiz-Chow A, Ramirez-Bermudez J. Aripiprazole in psychosis associated with Parkinson's disease. J Neuropsychiatry Clin Neurosci. 2005;17:421–422
  62. Mega MS, Cummings JL, Fiorello T, Gornbein J. The spectrum of behavioral changes in Alzheimer's disease. Neurology. 1996;46:130–135
  63. Beier MT. Treatment strategies for the behavioral symptoms of Alzheimer's disease: focus on early pharmacologic intervention. Pharmacotherapy. 2007;27:399–411
  64. Cohen-Mansfield J. Nonpharmacologic interventions for inappropriate behaviors in dementia: a review, summary, and critique. Am J Geriatr Psychiatry. 2001;9:361–381
  65. Grimmer T, Kurz A. Effects of cholinesterase inhibitors on behavioural disturbances in Alzheimer's disease: a systematic review. Drugs Aging. 2006;23:957–967
  66. Liepelt I, Maetzler W, Blaicher HP, et al. Treatment of dementia in parkinsonian syndromes with cholinesterase inhibitors. Dement Geriatr Cogn Disord. 2007;23:351–367
  67. Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev. 2006;CD003476
  68. Daiello LA. Atypical antipsychotics for the treatment of dementia-related behaviors: an update. Med Health R I. 2007;90:191–194
  69. Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA. 2005;293:596–608
  70. Deberdt WG, Dysken MW, Rappaport SA, et al. Comparison of olanzapine and risperidone in the treatment of psychosis and associated behavioral disturbances in patients with dementia. Am J Geriatr Psychiatry. 2005;13:722–730
  71. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006;355:1525–1538
  72. Tariot PN, Schneider L, Katz IR, et al. Quetiapine treatment of psychosis associated with dementia: a double-blind, randomized, placebo-controlled clinical trial. Am J Geriatr Psychiatry. 2006;14:767–776
  73. Mintzer JE, Tune LE, Breder CD, et al. Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. Am J Geriatr Psychiatry. 2007;15:918–931
  74. Haas SJ, Hill R, Krum H, et al. Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993-2003. Drug Saf. 2007;30:47–57
  75. Vieweg WV. New generation antipsychotic drugs and QTc interval prolongation. Prim Care Companion J Clin Psychiatry. 2003;5:205–215
  76. Hasnain M, Vieweg WVR, Fredrickson SK, et al. Clinical monitoring and management of the metabolic syndrome in patients receiving atypical antipsychotic medications. Prim Care Diabetes. 2009;3:5–15Epub 2008 Dec 10
  77. Bullock R. Treatment of behavioural and psychiatric symptoms in dementia: implications of recent safety warnings. Curr Med Res Opin. 2005;21:1–10
  78. FDA Public Health Advisory. Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances (April 11, 2005). http://www.fda.gov/Cder/drug/advisory/antipsychotics.htmAccessed September 24, 2008
  79. Bhasin M, Rowan E, Edwards K, McKeith I. Cholinesterase inhibitors in dementia with Lewy bodies: a comparative analysis. Int J Geriatr Psychiatry. 2007;22:890–895
  80. Edwards K, Royall D, Hershey L, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 24-week open-label study. Dement Geriatr Cogn Disord. 2007;23:401–405
  81. Rozzini L, Chilovi BV, Bertoletti E, et al. Cognitive and psychopathologic response to rivastigmine in dementia with Lewy bodies compared to Alzheimer's disease: a case control study. Am J Alzheimers Dis Other Demen. 2007;22:42–47
  82. Thomas AJ, Burn DJ, Rowan EN, et al. A comparison of the efficacy of donepezil in Parkinson's disease with dementia and dementia with Lewy bodies. Int J Geriatr Psychiatry. 2005;20:938–944
  83. FDA Approves the First Treatment for Dementia of Parkinson's Disease (June 27, 2006). http://www.fda.gov/bbs/topics/NEWS/2006/NEW01399.htmlAccessed September 24, 2008
  84. Miller LJ. The use of cognitive enhancers in behavioral disturbances of Alzheimer's disease. Consult Pharm. 2007;22:754–762
  85. Wynn ZJ, Cummings JL. Cholinesterase inhibitor therapies and neuropsychiatric manifestations of Alzheimer's disease. Dement Geriatr Cogn Disord. 2004;17:100–108
  86. Mori S, Mori E, Iseki E, Kosaka K. Efficacy and safety of donepezil in patients with dementia with Lewy bodies: preliminary findings from an open-label study. Psychiatry Clin Neurosci. 2006;60:190–195
  87. Sobow T. Parkinson's disease-related visual hallucinations unresponsive to atypical antipsychotics treated with cholinesterase inhibitors: a case series. Neurol Neurochir Pol. 2007;41:276–279
  88. Aarsland D, Hutchinson M, Larsen JP. Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia. Int J Geriatr Psychiatry. 2003;18:937–941
  89. Shea C, MacKnight C, Rockwood K. Donepezil for treatment of dementia with Lewy bodies: a case series of nine patients. Int Psychogeriatr. 1998;10:229–238

 Funding: None.

 Conflict of Interest: Dr Pandurangi is on the speaker's bureau of Astra-Zeneca, Bristol Myers Squibb, Janssen, and Pfizer Pharmaceuticals. The other authors do not have any potential conflict of interest to disclose.

 Authorship: All authors had access to the data and played a role in writing this manuscript.

PII: S0002-9343(09)00166-1

doi: 10.1016/j.amjmed.2009.01.025

The American Journal of Medicine
Volume 122, Issue 7 , Pages 614-622 , July 2009

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