Current Neurology and Neuroscience Reports

, Volume 6, Issue 6, pp 490–495 | Cite as

Psychotropic medication use for behavioral symptoms of dementia

  • Philip S. Wang
  • M. Alan Brookhart
  • Soko Setoguchi
  • Amanda R. Patrick
  • Sebastian Schneeweiss
Article

Abstract

Behavioral disturbances associated with dementia are common and burdensome. Although no psychotropic medications are currently approved by the US Food and Drug Administration (FDA) to treat such behavioral symptoms, a variety of drug classes are commonly used for these purposes. Atypical antipsychotic medications may be somewhat effective and are generally considered the pharmacologic treatments of choice; however “black box” warnings have recently been added to their labels by the FDA, warning of significantly increased risks of short-term mortality. Older conventional antipsychotic medications may also be somewhat effective but appear to pose risks that can be at least as great as those of the newer atypical drugs. Although antidepressants, benzodiazepines, mood stabilizers, acetylcholinesterase inhibitors, and N-methyl-D-aspartate (NMDA) receptor antagonists may be considered, particularly in patients with specific types of symptomatology, even less is known about their effectiveness and safety. Also, although various psychotropic medications used for behavioral disturbances in dementia patients may be somewhat effective, they have been increasingly associated with important safety risks.

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References and Recommended Reading

  1. 1.
    Hebert LE, Scherr PA, Bienias JL, et al.: Alzheimer disease in the US population: prevalence estimates using the 2000 Census. Arch Neurol 2003, 60:1119–1122.PubMedCrossRefGoogle Scholar
  2. 2.
    Mega MS, Cummings JL, Fiorello T, Gornbein J: The spectrum of behavioral changes in Alzheimer’s disease. Neurology 1996, 46:130–135.PubMedGoogle Scholar
  3. 3.
    Shin IS, Carter M, Masterman D, et al.: Neuropsychiatric symptoms and quality of life in Alzheimer’s disease. Am J Geriatr Psychiatry 2005, 13:469–474. This is a careful assessment of the quality of life in both patients with dementia as well as their caregivers, demonstrating that the presence of behavioral symptoms adversely affects both.PubMedCrossRefGoogle Scholar
  4. 4.
    Phillips VL, Diwan S: The incremental effect of dementiarelated problem behaviors on the time to nursing home placement in poor, frail, demented older people. J Am Geriatr Soc 2003, 51:188–193.PubMedCrossRefGoogle Scholar
  5. 5.
    Wolstenholm J, Fenn P, Gray A, et al.: Estimating the relationship between disease progression and cost of care in dementia. Br J Psychiatry 2002, 181:36–42.CrossRefGoogle Scholar
  6. 6.
    Rabins PV, Lyketsos CG, Steele CD: Practical Dementia Care. New York: Oxford University Press; 1999.Google Scholar
  7. 7.
    Beeri MS, Werner P, Davidson M, Noy S: The cost of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Alzheimer’s disease patients. Int J Geriatr Psychiatry 2002, 17:403–408.PubMedCrossRefGoogle Scholar
  8. 8.
    Beck C: Psychosocial and behavioral interventions for Alzheimer’s disease patients. Am J Geriatr Psychiatry 1998, 6(2 Suppl 1):S41-S48.PubMedGoogle Scholar
  9. 9.
    Snowden M, Sato K, Roy-Byrne P: Assessment and treatment of nursing home residents with depression or behavioral symptoms associated with dementia: a review of the literature. J Am Geriatr Soc 2003, 51:1305–1317.PubMedCrossRefGoogle Scholar
  10. 10.
    Cummings JL: Behavioral and neuropsychiatric outcomes in Alzheimer’s disease. CNS Spectrums 2005, 10(11 Suppl 18):22–25.PubMedGoogle Scholar
  11. 11.
    Cody M, Beck C, Svarstatd BL: Challenges to the use of non-pharmacologic interventions in nursing homes. Psychiatry Serv 2002, 53:1397–1401.CrossRefGoogle Scholar
  12. 12.
    Giron MS, Forsell Y, Bernsten C, et al.: Psychotropic drug use in elderly people with and without dementia. Int J Geriatr Psychiatry 2001, 16:900–906.PubMedCrossRefGoogle Scholar
  13. 13.
    Schorr RI, Fought RL, Ray WA: Changes in antipsychotic drug use in nursing homes during implementation of the OBRA-87 regulations. JAMA 1994, 271:358–362.CrossRefGoogle Scholar
  14. 14.
    Breisacher BA, Limcangco R, Simoni-Wastila L, et al.: The quality of antipsychotic drug prescribing in nursing homes. Arch Intern Med 2005, 165:1280–1285. This is a timely examination of Medicare beneficiaries in nursing homes, revealing that antipsychotic medication use in these settings is rising but often suboptimal.CrossRefGoogle Scholar
  15. 15.
    Sink KM, Holden KF, Yaffe K: Pharmacological treatment of neuropsychiatric symptoms of dementia. JAMA 2005, 283:596–608. This recent and comprehensive review of the evidence concerning pharmacologic agents for behavioral symptoms in dementia patients reveals that these treatments may be only marginally effective and carry important risks.CrossRefGoogle Scholar
  16. 16.
    Jeste DV, Sable JA, Salzman C: Treatment of late-life disordered behavior, agitation, and psychosis. In Clinical Geriatric Psychopharmacology, edn 4. Edited by Salzman C. Philadelphia: Lippincott, Williams & Wilkins; 2005:129–195. These authors are perhaps the foremost experts in this area and their recent review is not only thorough and rigorous but also filled with practical wisdom for clinicians.Google Scholar
  17. 17.
    Kindermann SS, Dolder CR, Bailey A, et al.: Pharmacologic treatment of psychosis and agitation in elderly patients with dementia. Drugs Aging 2002, 19:257–276.PubMedCrossRefGoogle Scholar
  18. 18.
    Alexopoulos GS, Streim J, Carpenter D, Docherty JP: Using antipsychotic agents in older patients: Expert Consensus Panel for Using Antipsychotic Drugs in Older Patients. J Clin Psychiatry 2004, 65(Suppl 2):5–99. This is an excellent synthesis of the literature and a survey of American opinion leaders. It provides much-needed guidelines for difficult clinical dilemmas involving antipsychotics used for geriatric psychiatric disorders.PubMedGoogle Scholar
  19. 19.
    U.S. Food and Drug Administration: FDA Public Health Advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. Available at: www.fda. gov/cder/drug/advisory/antipsychotics.htm. Accessed on April 15, 2005. This public health advisory issued by the FDA raised the first warnings of increased short-term mortality from atypical antipsychotic medications in elderly dementia patients.Google Scholar
  20. 20.
    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, 294:1934 -1943. This meta-analysis provides the most comprehensive, publicly available information to date on the hazards of short-term mortality from atypical antipsychotic medications in dementia patients. It is also one of the few sources of clinical trial data shedding light on the mortality associated with the conventional agent haloperidol.PubMedCrossRefGoogle Scholar
  21. 21.
    Brodaty H, Ames D, Snowdon J, et al.: A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry 2003, 64:134 -143.PubMedCrossRefGoogle Scholar
  22. 22.
    Sponsor’s website for Risperdal. Available at: http://www.risperdal.com. Accessed March 24, 2006.Google Scholar
  23. 23.
    Sponsor’s website for Zyprexa. Available at: http://www.zyprexa.com. Accessed March 24, 2006.Google Scholar
  24. 24.
    Sponsor’s website for Abilify. Available at: http://www.abilify.com. Accessed March 24, 2006.Google Scholar
  25. 25.
    Ballard C, Waite J: The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer’s disease. Cochrane Database of Systematic Reviews, Volume 1, 2006. Accession number 00075320-1000000000-02414.Google Scholar
  26. 26.
    Merrill DB, Dec GW, Goff DC: Adverse cardiac effects associated with clozapine. J Clin Psychopharmacol 2005, 25:32–41. This is a thoughtful review of potential adverse cardiac effects from clozapine that includes a consideration of these rare risks versus the potential benefits from clozapine use.PubMedCrossRefGoogle Scholar
  27. 27.
    Kelly HG, Fay JE, Lavery SG: Thioridazine hydrochloride (Mellaril): its effects on the electrocardiogram and a report of two fatalities with electrocardiographic abnormalities. Can Med Assoc J 1963, 89:546–554.PubMedGoogle Scholar
  28. 28.
    Hennessy S, Bilker WB, Knauss JS, et al.: Cardiac arrest and ventricular arrhythmia in patients taking antipsychiotic drugs: cohort study using administrative data. BMJ 2002, 325:1070–1074.PubMedCrossRefGoogle Scholar
  29. 29.
    Straus SM, Bleumink GS, Dieleman JP, et al.: Antipsychotics and the risk of sudden cardiac death. Arch Intern Med 2004, 164:1293–1297.PubMedCrossRefGoogle Scholar
  30. 30.
    Reilly JG, Ayis SA, Ferrier IN, et al.: Thioridazine and sudden unexplained death in psychiatric inpatients. Br J Psychiatry 2002, 180:515–522.PubMedCrossRefGoogle Scholar
  31. 31.
    Ray WA, Meredith S, Thapa PB, et al.: Antipsychotics and the risk of sudden cardiac death. Arch Gen Psychiatry 2001, 58:1161–1167.PubMedCrossRefGoogle Scholar
  32. 32.
    Glassman AH, Bigger JT: Antipsychotic drugs: prolonged QTc Interval, Torsade de Pointes, and sudden death. Am J Psychiatry 2001, 158:1774 -1782.PubMedCrossRefGoogle Scholar
  33. 33.
    Rapoport M, Muhammad M, Shulman KI, et al.: Antipsychotic use in the elderly: shifting trends and increasing costs. Int J Geriatr Psychiatry 2005, 20:749–753. This is an informative analysis shedding light on the temporal changes in antipsychotic use among elderly patients that have been occurring recently.PubMedCrossRefGoogle Scholar
  34. 34.
    Strong C: Antipsychotic use in elderly patients with dementia prompts new FDA warning. Neuropsychiatry Rev 2005, 6:1–17.Google Scholar
  35. 35.
    Dewa CS, Remington G, Herrmann N, et al.: How much are atypical antipsychotic agents being used, and do they reach the populations who need them?: a Canadian experience. Clin Therapeut 2002, 24:1466–1476.CrossRefGoogle Scholar
  36. 36.
    Kuehn BM: FDA warns antipsychotic drugs may be risky for elderly. JAMA 2005, 293:2462.PubMedCrossRefGoogle Scholar
  37. 37.
    Chan YC, Pariser SF, Neufeld G: Atypical antipsychotics in older adults. Pharmacotherapy 1999, 19:811–822.PubMedCrossRefGoogle Scholar
  38. 38.
    Tariot PN: The older patient: the ongoing challenge of efficacy and tolerability. J Clin Psychiatry 1999, 60(Suppl 23):29–33.PubMedGoogle Scholar
  39. 39.
    Maixner SM, Mellow AM, Tandon R: The efficacy, safety, and tolerability of antipsychotics in the elderly. J Clin Psychiatry 1999, 60(Suppl 8):29–41.PubMedGoogle Scholar
  40. 40.
    Lawlor B: Behavioral and psychological symptoms in dementia: the role of atypical antipsychotics. J Clin Psychiatry 2004, 65(Suppl 11):5–10.PubMedGoogle Scholar
  41. 41.
    Wang PS, Schneeweiss S, Avorn J, et al.: Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005, 353:2335–2341. This is a recent observational study of a question that has not been possible to answer through clinical trial data—namely, how the mortality risks from conventional antipsychotics compare with those from atypical agents in elderly patients.PubMedCrossRefGoogle Scholar
  42. 42.
    Nasrallah HA, White T, Nasrallah AT: Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data. Am J Geriatr Psychiatry 2004, 12:437–439. This is another recent observational study suggesting that the mortality associated with conventional agents in elderly patients may be at least as great as that from atypical patients.PubMedCrossRefGoogle Scholar
  43. 43.
    Liperoti R, Gambassi G, Lapane KL, et al.: Conventional and atypical antipsychotics and the risk of hospitalization for ventricular arrhythmias or cardiac arrest. Arch Intern Med 2005, 165:696–701. This is a recent pharmacoepidemiologic study that found conventional but not atypical antipsychotic agents increased the risks of arrhythmias and cardiac arrest.PubMedCrossRefGoogle Scholar
  44. 44.
    Kozma C, Engelhart L, Long S, et al.: Absence of risperidone-related increased stroke risk in dementia patients. New Research Abstract 880. 2004 Annual Meeting of the American Psychiatric Association. http://www.psych.org/public_info/libr_pub/abstracts. Accessed May 28, 2006. This recent abstract reported no significant differences in stroke risk between atypical and conventional antipsychotic agents in elderly dementia patients.Google Scholar
  45. 45.
    Herrmann N, Mamdani M, Lanctot KL: Atypical antipsychotics and the risk of cerebrovascular accidents. Am J Psychiatry 2004, 161:1113–1115. This observational study also reported on significant difference in stroke risk between atypical and conventional antipsychotics.PubMedCrossRefGoogle Scholar
  46. 46.
    Liperoti R, Gambassi G, Lapane KL, et al.: Cerebrovascular events among elderly nursing home patients treated with conventional or atypical antipsychotics. J Clin Psychiatry 2005, 66:1090–1096. This observational study failed to detect significantly elevated risks of cerebrovascular events from either atypical or conventional antipsychotic use relative to no use.PubMedCrossRefGoogle Scholar
  47. 47.
    Pollock GB, Mulsant BH, Rosen J: Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbance in hospitalized, demented patients. Am J Psychiatry 2002, 159:460–465.PubMedCrossRefGoogle Scholar
  48. 48.
    Lyketsos CG, DelCampo L, Steinberg M, et al.: Treating depression in Alzheimer’s disease: efficacy and safety of sertraline therapy and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry 2003, 60:737–746.PubMedCrossRefGoogle Scholar
  49. 49.
    Finkel SI, Mintzer JE, Dysken M, et al.: A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer’s disease in outpatients treated with donepezil. Int J Geriatr Psychiatry 2004, 19:9–18.PubMedCrossRefGoogle Scholar
  50. 50.
    Martinon-Torres G, Fioravanti M, Grimley EJ: Trazodone for agitation in dementia. Cochrane Database Syst Rev 2004, CD004990.Google Scholar
  51. 51.
    Thapa PB: Antidepressants and the risk of falls among nursing home residents. N Engl J Med 1998, 339:875–882.PubMedCrossRefGoogle Scholar
  52. 52.
    Meehan KM, Wang H, David SR, et al.: Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology 2002, 26:494–504.PubMedCrossRefGoogle Scholar
  53. 53.
    Stotsky B: Psychosis in the elderly. In Psychopharmacology and Aging: Advances in Behavioral Biology, vol 6. Edited by Eisdorfer C, Faun WE. New York: Plenum; 1973.Google Scholar
  54. 54.
    Jackson CW, Pitner JK, Mintzer JE: Zolpidem for the treatment of agitation in elderly demented patients. J Clin Psychiatry 1996, 57:372–373.PubMedGoogle Scholar
  55. 55.
    Ray WA, Griffin MR, Schaffner W, et al.: Psychotropic drug use and the risk of hip fracture. N Engl J Med 1987, 316:363–369.PubMedCrossRefGoogle Scholar
  56. 56.
    Wang PS, Bohn RL, Glynn RJ, et al.: Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry 2001, 158:892–898.PubMedGoogle Scholar
  57. 57.
    Wang PS, Bohn RL, Glynn RJ, et al.: Zolpidem use and hip fractures in the elderly. J Am Geriatr Soc 2001, 49:1685–1690.PubMedCrossRefGoogle Scholar
  58. 58.
    Cummings JL, Schneider E, Tariot PN, Graham SM: Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 2006, 67:57–63. This is a very recent trial shedding light on the efficacy and safety of the NMDA receptor antagonist memantine when used for behavioral disturbances in dementia patients.PubMedCrossRefGoogle Scholar
  59. 59.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2006

Authors and Affiliations

  • Philip S. Wang
    • 1
  • M. Alan Brookhart
  • Soko Setoguchi
  • Amanda R. Patrick
  • Sebastian Schneeweiss
  1. 1.Department of Psychiatry and Division of Pharmacoepidemiology and PharmacoeconomicsBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA

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