Abstract
The behavioral and psychological symptoms of dementia (BPSD), such as psychosis, agitation, or aggression have a considerable negative impact on the quality of life of both patients and their caregivers. Multiple studies have demonstrated that atypical antipsychotics are efficacious in the treatment of the aggressive and psychotic symptom clusters, and here we review their use in this indication. Because of the safety concerns associated with the use of atypical antipsychotics in this population, these drugs must be usedjudiciously. For patients with severe BPSD such as psychosis, agitation, or aggression, for whom there are few options, atypical antipsychotics, particularly risperidone and olanzapine, should be considered.
Keywords: dementia, BPSD, atypical antipsychotic
Full Text
The Full Text of this article is available as a PDF (1.6 MB).
References
- 1. Finkel SI: Introduction to behavioral and psychological symptoms of dementia (BPSD). Int JGeriatrPsychiatry. 2000; 15(Suppl 1): S2-S4. [DOI] [PubMed] [Google Scholar]
- 2. Small GW, Rabins PV, Barry PP, et al.: Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society. JAAM. 1997; 278: 1363-1371. [PubMed] [Google Scholar]
- 3. Finkel SI: Behavioral and psychological symptoms of dementia: A current focus for clinicians, researchers, and caregivers. J Clin Psychiatry. 2001; 62(Suppl 21): 3-6. [PubMed] [Google Scholar]
- 4. Hemels ME, Lanctot KL, Iskedjian M, et al.: Clinical and economic factors in the treatment of behavioral and psychological symptoms of dementia. Drugs Aging. 2001; 18: 527-550. [DOI] [PubMed] [Google Scholar]
- 5. Cummings JL, Mega M, Gray K, et al.: The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology. 1994; 44: 2308-2314. [DOI] [PubMed] [Google Scholar]
- 6. Cohen-Mansfield J: Nonpharmacologic interventions for inappropriate behaviors in dementia. Am J Geriatr Psychiatry. 2001; 9: 361-381. [PubMed] [Google Scholar]
- 7. McShane RH: What are the syndromes of behavioral and psychological symptoms of dementia? Int Psychogeriatr. 2000; 12(Suppl 1): 147-153. [Google Scholar]
- 8. Tariot PN, Blazina L: The psychopathology of dementia. In Morris TC (ed): Handbook of Dementing Illnesses. New York: Marcel Dekker, 1994. [Google Scholar]
- 9. Steele C, Rovner B, Chase GA, et al.: Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease. Ain J psychiatry. 1990; 147: 1049-1051. [DOI] [PubMed] [Google Scholar]
- 10. Balestreri L, Grossberg A, Grossberg GT: Behavioral and psychological symptoms of dementia as a risk factor for nursing home placement. nt Psychogeriatr. 2000; 12(Suppl 1): 59-62. [Google Scholar]
- 11. Teri L, Rabins P. Whitehouse P. et al.: Management of behavior disturbance in Alzheimer disease: Current knowledge and future directions. Alzheimer Dis Assoc Disord. 1992; 6: 77-88. [DOI] [PubMed] [Google Scholar]
- 12. Herrmann N, Lanctot KL, Naranjo CA: Behavioural disorders in demented elderly patients. CNS Drugs. 1996; 6: 280-300. [Google Scholar]
- 13. De Deyn PP, Wirshing WC: Scales to assess efficacy and safety of pharmacologic agents in the treatment of behavioral and psychological symptoms of dementia. J Clin Psychiatry. 2001; 62(Suppl 21): 19-22. [PubMed] [Google Scholar]
- 14. Reisberg B, Borenstein J, Salob SP, et al.: Behavioral symptoms in Alzheimer's disease: Phenomenology and treatment. J Clin Psychiatry. 1987; 48(Suppl): 9-15. [PubMed] [Google Scholar]
- 15. Cohen-Mansfield J: Conceptualization of agitation: Results based on the Cohen-Mansfield Agitation Inventory and the Agitation Behavior Mapping Instrument. Int Psychogeriatr. 1996; 8(Suppl 3): 309-315. [DOI] [PubMed] [Google Scholar]
- 16. Dahlke F, Lohaus A, Gutzmann H: Reliability and clinical concepts underlying global judgments in dementia: Implications for clinical research. Psychopharmacol Bull. 1992; 28: 425-432. [PubMed] [Google Scholar]
- 17. Overall JE, Gorham DR: The Brief Psychiatric Rating Scale. Psychol Rep. 1962; 10: 799-812. [Google Scholar]
- 18. Herrmann N: Recommendations for the management of behavioral and psychological symptoms of dementia. Can JNeurol Sci. 2001; 28(Suppl 1): S96-S107. [DOI] [PubMed] [Google Scholar]
- 19. Sink KM, Holden KF, Yaffe K: Pharmacological treatment of neuropsychiatric symptoms of dementia: A review of the evidence. JAMA. 2005; 293: 596-608. [DOI] [PubMed] [Google Scholar]
- 20. Gauthier S, Feldman H, Hecker J, et al.: Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. Int Psychogeriatr. 2002; 14: 389-404. [DOI] [PubMed] [Google Scholar]
- 21. Paleacu D, Mazeh D, Mirecki I, et al.: Donepezil for the treatment of behavioral symptoms in patients with Alzheimer's disease. Clin Neuropharmacol. 2002; 25: 313-317. [DOI] [PubMed] [Google Scholar]
- 22. Weiner MF, Martin-Cook K, Foster BM, et al.: Effects of donepezil on emotional/behavioral symptoms in Alzheimer's disease patients. J Clin Psychiatry. 2000; 61: 487-492. [DOI] [PubMed] [Google Scholar]
- 23. Tariot PN, Cummings JL, Katz IR, et al.: A randomized, doubleblind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. JAm Geriatr Soc. 2001; 49: 1590-1599. [PubMed] [Google Scholar]
- 24. Wilcock G, Howe I, Coles H, et al.: A long-term comparison of galantamine and donepezil in the treatment of Alzheimer's disease. Drugs Aging. 2003; 20: 777-789. [DOI] [PubMed] [Google Scholar]
- 25. Suh GH, Yeon Jung H, Uk Lee C, et al.: A prospective, doubleblind, community-controlled comparison of three doses of galantamine in the treatment of mild to moderate Alzheimer's disease in a Korean population. Clin Therap. 2004; 26: 1608-1618. [DOI] [PubMed] [Google Scholar]
- 26. Cummings JL, Schneider L, Tariot PN, et al.: Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer's disease. Am JPsychiatry. 2004; 161: 532-538. [DOI] [PubMed] [Google Scholar]
- 27. Tariot PN, Solomon PR, Morris JC, et al.: A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-IO Study Group. Neurology. 2000; 54: 2269-2276. [DOI] [PubMed] [Google Scholar]
- 28. Schneider LS, Pollock VE, Lyness SA: A meta-analysis of controlled trials of neuroleptic treatment in dementia. JAm Geriatr Soc. 1990; 38: 553-563. [DOI] [PubMed] [Google Scholar]
- 29. Zaudig M: A risk-benefit assessment of risperidone for the treatment of behavioral and psychological symptoms in dementia. Drug Safety. 2000; 23: 183-195. [DOI] [PubMed] [Google Scholar]
- 30. Lawlor B, Bhriain SN: Psychosis and behavioral symptoms of dementia: Defining the role of neuroleptic interventions. IntJGeriatr Psychiatry. 2001; 16(Suppl 1): S2-S6. [DOI] [PubMed] [Google Scholar]
- 31. Jeste DV, Rockwell E, Harris MJ, et al.: Conventional vs newer antipsychotics in elderly patients. Am J Geriatr Psychiatry. 1999; 7: 70-76. [PubMed] [Google Scholar]
- 32. Katz IR, Jeste DV, Mintzer JE, et al.: Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: A randomized, double-blind trial. J Clin Psychiatry. 1999; 60: 107-115. [DOI] [PubMed] [Google Scholar]
- 33. De Deyn PP, Rabheru K, Rasmussen A, et al.: A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology. 1999; 53: 946-955. [DOI] [PubMed] [Google Scholar]
- 34. Chan WC, Lam LC, Choy CN, et al.: A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioral and psychological symptoms in Chinese dementia patients. IntJ Geriatr Psychiatry. 2001; 16: 1156-1162. [DOI] [PubMed] [Google Scholar]
- 35. Brodaty H, Ames D, Snowdon J, et al.: A randomized placebocontrolled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry. 2003; 64: 134-143. [DOI] [PubMed] [Google Scholar]
- 36. Suh GH, Son HG, Ju YS, et al.: A randomized, double-blind, crossover comparison of risperidone and haloperidol in Korean dementia patients with behavioral disturbances. Am J Geriatr Psychiatry. 2004; 12: 509-516. [DOI] [PubMed] [Google Scholar]
- 37. De Deyn PP, Katz IR, Brodaty H, et al.: Management of agitation, aggression, and psychosis associated with dementia: A pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone. Clin Neurol Neurosurg. 2005; 107: 497-508. [DOI] [PubMed] [Google Scholar]
- 38. Street JS, Clark WS, Gannon KS, et al.: Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: A double-blind, randomized, placebocontrolled trial. Arch Gen Psychiatry. 2000; 57: 968-976. [DOI] [PubMed] [Google Scholar]
- 39. De Deyn PP, Carrrasco MM, Deberdt W, et al.: Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 2004; 9: 115-126. [DOI] [PubMed] [Google Scholar]
- 40. Clark WS, Street JS, Feldman PD, et al.: The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer's disease. J Clin Psychiatry. 2001; 62: 34-40. [DOI] [PubMed] [Google Scholar]
- 41. Rainer MK, Mucke HA, Kruger-Rainer C, et al.: Zotepine for behavioral and psychological symptoms in dementia: An open-label study. CNS Drugs. 2004; 18: 49-55. [DOI] [PubMed] [Google Scholar]
- 42. Fujikawa T, Takahashi T, Kinoshita A, et al.: Quetiapine treatment for behavioral and psychological symptoms in patients with senile dementia of Alzheimer type. Neuropsychobiology. 2004; 49: 201-204. [DOI] [PubMed] [Google Scholar]
- 43. Scharre DW, Chang SI: Cognitive and behavioral effects of quetiapine in Alzheimer disease patients. Alzheimer Dis Assoc Disord. 2002; 16: 128-130. [DOI] [PubMed] [Google Scholar]
- 44. McManus DQ, Arvanitis LA, Kowalcyk BB: Quetiapine, a novel antipsychotic: Experience in elderly patients with psychotic disorders. Seroquel Trial 48 Study Group. J Clin Psychiatry. 1999; 60: 292-298. [PubMed] [Google Scholar]
- 45. Tariot PN, Salzman C, Yeung PP, ei al.: Long-term use of quetiapine in elderly patients with psychotic disorders. Clin Therap. 2000; 22: 1068-1084. [DOI] [PubMed] [Google Scholar]
- 46. Ballard C, Margallo-Lana M, Juszczak E, et al.: Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: Randomised double blind placebo controlled trial. BMJ. 2005; 330: 874-874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47. De Deyn P, Jeste DV, Swanink R, et al.: Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: A randomized, placebo-controlled study. J Clin Psychopharmacol. 2005; 25: 463-467. [DOI] [PubMed] [Google Scholar]
- 48. Baskys A: Lewy body dementia: The litmus test for neuroleptic sensitivity and extrapyramidal symptoms. J Clin Psychiatry. 2004; 65(Suppl 11): 16-22. [PubMed] [Google Scholar]
- 49. Mulsant BH, Gharabawi GM, Bossie CA, et al.: Correlates of anticholinergic activity in patients with dementia and psychosis treated with risperidone or olanzapine. J Clin Psychiatry. 2004; 65: 1708-1714. [DOI] [PubMed] [Google Scholar]
- 50. Gareri P, Cotroneo A, Lacava R, et al.: Comparison of the efficacy of new and conventional antipsychotic drugs in the treatment of behavioral and psychological symptoms of dementia (BPSD). Arch Gerontol Geriatr Suppl. 2004; 9: 207-215. [DOI] [PubMed] [Google Scholar]
- 51. Fontaine CS, Hynan LS, Koch K, et al.: A double-blind comparison of olanzapine versus risperidone in the acute treatment of dementia-related behavioral disturbances in extended care facilities. J Clin Psychiatry. 2003; 64: 726-730. [DOI] [PubMed] [Google Scholar]
- 52. Schneider LS, Tariot PN, Lyketsos CG; et al.: National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE): Alzheimer disease trial methodology. Am J Geriatr Psychiatry. 2001; 9: 346-360. [PubMed] [Google Scholar]
- 53. McShane R, Keene J, Gedling K, et al.: Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up. BMJ. 1997; 314: 266-270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54. Saxton J, McGonigle-Gibson K, Swihart A, et al.: Assessment of severely impaired patients: Description and validation of a new neuropsychological test battery. PsycholAssess. 1990; 2: 298-303. [Google Scholar]
- 55. http.//www.fda.gov/cder/drug/advisory/antipsychotics.htm. Accessed April 11, 2005.
- 56. Schneider LS, Dagerman KS, Insel P: Risk of death with atypical antipsychotic drug treatment for dementia. Meta-analysis of randomized placebo-controlled trials. JAMA4. 2005; 294: 1934-1943. [DOI] [PubMed] [Google Scholar]
- 57. Wooltorton E. Risperidone (Risperdal): Increased rate of cerebrovascular adverse events in dementia trials. Can Med Assoc J. 2002; 167: 1269-1270. [PMC free article] [PubMed] [Google Scholar]
- 58. Wooltorton E. Olanzapine (Zyprexa): Increased incidence of cerebrovascular events in dementia trials. Can Med Assoc J 2004; 170: 1395-1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59. Abilify package insert. Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc.; 2005. [Google Scholar]
- 60. Herrmann N, Lanct6t KL. Do atypical antipsychotics cause stroke? CNSDrugs. 2005; 19: 91-103. [DOI] [PubMed] [Google Scholar]
- 61. Sleeper RB: Antipsychotic dose-sparing effect with addition of memantine. Ann Pharmacother. 2005; 39: 1573-1576. [DOI] [PubMed] [Google Scholar]
- 62. Zhao Q, Xie C, Pesco-Koplowitz L, et al.: Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil. J Clin Pharmacol. 2003; 43: 180-186. [DOI] [PubMed] [Google Scholar]
- 63. Weiser M, Rotmensch HH, Korczyn AD, et al.: A pilot, randomized, open-label trial assessing safety and pharmacokinetic parameters of co-administration of rivastigmine with risperidone in dementia patients with behavioral disturbances. Int JGeriatr Psychiatry. 2002; 17: 343-346. [DOI] [PubMed] [Google Scholar]
- 64. Huang F, Lasseter KC, Janssens L, et al.: Pharmacokinetic and safety assessments of galantamine and risperidone after thetwo drugs are administered alone and together. J Clin Pharmacol. 2002; 42: 1341-1351. [DOI] [PubMed] [Google Scholar]