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Treatment of Behavioral and Psychological Symptoms of Alzheimer’s Disease

  • Cognitive Disorders (M Geschwind, Section Editor)
  • Published:
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Opinion statement

Behavioral and psychological symptoms of dementia (BPSD) are frequent amongst people with Alzheimer’s disease (AD) and other dementias, commonly confer risk to that person and others, and present a significant management challenge for clinicians. There is increasing evidence to support the value of simple psychological interventions and the treatment of pain as a first-line management strategy prior to pharmacotherapy. The most widely prescribed pharmacological treatments—atypical antipsychotics—have a modest but significant beneficial effect in the short-term treatment of aggression (over 6–12 weeks) but limited benefits in longer-term therapy. In addition, there have been increasing concerns regarding the potential for serious adverse outcomes, including stroke and death. The potential pharmacologic alternatives to atypical antipsychotics with the most encouraging preliminary evidence include memantine, carbamazepine, citalopram, and prazosin. Large, prospective, randomized placebo-controlled trials are needed to establish the role of these agents as clinical therapies for the treatment of BPSD.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Alzheimer’s Disease International Fact Sheet: The prevalence of dementia worldwide. December 2008. Available at www.alz.co.uk/adi/pdf/prevalence.pdf.

  2. Steinberg M, Shao H, Zandi P, et al. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry. 2008;23:170–7.

    Article  PubMed  Google Scholar 

  3. Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. IV: disorders of behaviour. Br J Psych. 1990;157:86–94.

    Article  CAS  Google Scholar 

  4. Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psych. 2000;157:708–14.

    Article  CAS  Google Scholar 

  5. Margallo-Lana M, Swann A, O’Brien J, et al. Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. Int J Geriatric Psych. 2001;16:39–44.

    Article  CAS  Google Scholar 

  6. Lyketsos CG. Neuropsychiatric symptoms (behavioral and psychological symptoms of dementia) and the development of dementia treatments. Int Psychogeriatr. 2007;19:409–20.

    Article  PubMed  Google Scholar 

  7. Gilley DW, Whalen ME, Wilson RS, Bennett DA. Hallucinations and associated factors in Alzheimer’s disease. J Neuropsych & Clin Neurosci. 1991;3:371–6.

    CAS  Google Scholar 

  8. Rabins PV, Mace NL, Lucas MJ. The impact of dementia on the family. JAMA. 1982;248:333–5.

    Article  PubMed  CAS  Google Scholar 

  9. Ballard CG, Patel A, Solis M, Lowe K, Wilcock G. A follow up study of depression in the carers of dementia sufferers. BMJ. 1996;312:947.

    Article  PubMed  CAS  Google Scholar 

  10. Banerjee S, Smith SC, Lamping DL, et al. Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia. J Neurol, Neurosurg Psych. 2006;77:146–8.

    Article  CAS  Google Scholar 

  11. Steele C, Rovner B, Chase GA, Folstein M. Psychiatric symptoms and nursing home placement of patients with Alzheimer’s disease. Am J Psych. 1990;147:1049–51.

    CAS  Google Scholar 

  12. Holroyd S, Laurie S. Correlates of psychotic symptoms among elderly outpatients. Int J Geriatric Psych. 1999;14:379–84.

    Article  CAS  Google Scholar 

  13. Chapman FM, Dickinson J, McKeith I, Ballard C. Association among visual hallucinations, visual acuity, and specific eye pathologies in Alzheimer’s disease: treatment implications. Am J Psych. 1999;156:1983–5.

    CAS  Google Scholar 

  14. Cohen-Mansfield J, Lipson S. The utility of pain assessment for analgesic use in persons with dementia. Pain. 2008;134:16–23.

    Article  PubMed  Google Scholar 

  15. Husebo B, Ballard C, Sandvik R, Nilsen OB, Aarsland D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343:d4065 (Class B evidence).

    Article  PubMed  Google Scholar 

  16. Lyketsos CG, Colenda CC, Beck C, et al. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia due to Alzheimer disease. Am J Geriatr Psych. 2006;14:561–72.

    Article  Google Scholar 

  17. Cohen-Mansfield J, Libin A, Marx MS. Nonpharmacological treatment of agitation: a controlled trial of systematic individualized intervention. J Gerontol A Biol Sci Med Sci. 2007;62:908–16 (Class B evidence).

    Article  PubMed  Google Scholar 

  18. Cohen-Mansfield J, Werner P. Management of verbally disruptive behaviors in nursing home residents. J Gerontol Series A-Biol Sci Med Sci. 1997;52:369–77 (Class B evidence).

    Article  Google Scholar 

  19. Ballard C, Brown R, Fossey J, et al. Brief psychosocial therapy for the treatment of agitation in alzheimer disease (The CALM-AD Trial). Am J Geriatr Psychiatr. 2009;17:726–33 (Class C evidence).

    Article  Google Scholar 

  20. Bird M. Psychosocial approaches to challenging behaviour in dementia: a controlled trial. In: Report to the Commonwealth Department of Health and Ageing. Canberra: Office for Older Australians 2002. (Class B evidence).

  21. Fossey J, Ballard C, Juszczak E, et al. Effect of enhanced psychosocial care on antipsychotic use in nursing home residents with severe dementia: cluster randomised trial. BMJ. 2006;332:756–8 (Class B evidence).

    Article  PubMed  Google Scholar 

  22. Ballard C, Powell I, James I, et al. Can psychiatric liaison reduce neuroleptic use and reduce health service utilization for dementia patients residing in care facilities. Int J Geriatric Psych. 2002;17:140–5.

    Article  Google Scholar 

  23. Chenoweth L, King MT, Jeon YH, et al. Caring for Aged Dementia Care Resident Study (CADRES) of person-centred care, dementia-care mapping, and usual care in dementia: a cluster-randomised trial. Lancet Neurol. 2009;8:317–25. (Class B evidence).

    Article  PubMed  Google Scholar 

  24. The Use of Antipsychotic medication for people with dementia: Time for Action. A report For the Minister of State for Care Services by Professor Sube Banerjee, 2009. www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108302.pdf.

  25. Deaths with antipsychotics in elderly patients with behavioral disturbances. U.S. Food and Drug Administration, FDA Public Health Advisory, Centre for Drug Evaluation and Research. FDA 13-7–2005.

  26. Information for Healthcare Professionals: Conventional Antipsychotics FDA ALERT [6/16/2008] www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm.

  27. Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci. 2006;7:492–500 (Class A evidence).

    Article  PubMed  CAS  Google Scholar 

  28. Tune LE, Steele C, Cooper T. Neuroleptic drugs in the management of behavioral symptoms of Alzheimer’s disease. Psych Clinics North America. 1991;14:353–73 (Class C evidence).

    CAS  Google Scholar 

  29. Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SHL. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet. 2000;355:1048–52 (Class C evidence).

    Article  PubMed  CAS  Google Scholar 

  30. Hollis J, Grayson D, Forrester L, Brodaty H, Touyz S, Cumming R. Antipsychotic medication dispensing and risk of death in veterans and war widows 65 years and older. Am J Geriatric Psych 2007;932–41. (Class C evidence).

  31. Wang PS, Schneeweiss S, Avorn J, Fischer MA, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. New Engl J Med. 2005;353:2335–41 (Class C evidence).

    Article  PubMed  CAS  Google Scholar 

  32. Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatric Psych. 2006;14:191–210 (Class A evidence).

    Google Scholar 

  33. Zhong KX, Tariot PN, Mintzer J, Minkwitz MC, Devine NA, et al. Quetiapine to treat agitation in dementia: a randomized double-blind placebo controlled study. Curr Alzheimer Res. 2007;4:81–93 (Class B evidence).

    Article  PubMed  CAS  Google Scholar 

  34. 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 Geriatric Psych. 2007;15:918–31 (Class B evidence).

    Article  Google Scholar 

  35. Ballard C, Margallo-Lana M, Juszczak E, et al. Quetiapine and rivastigmine and cognitive decline in Alzheimer’s disease: randomized double blind placebo controlled trial. BMJ. 2005;330:874 (Class B evidence).

    Article  PubMed  CAS  Google Scholar 

  36. Ballard C, Lana MM, Theodoulou M, et al. Investigators DART AD. A randomized, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial). PLoS Medicine/Public Library of Science. 2008;5:76 (Class B evidence).

    Article  Google Scholar 

  37. Schneider LS, Tariot PN, Dagerman KS, et al. CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. New Engl J Med. 2006;355:1525–3830 (Class B evidence).

    Article  PubMed  CAS  Google Scholar 

  38. 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;294:1934–43 (Class A evidence).

    Article  PubMed  CAS  Google Scholar 

  39. Ballard C, Hanney ML, Theodoulou M, et al. DART-AD investigators. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomized placebo- controlled trial. Lancet Neurol. 2009;8:151–7. (Class A evidence).

    Article  PubMed  CAS  Google Scholar 

  40. Angelucci F, Bernadini S, Gravina P, et al. Délusion symptômes and réponse to antipsychotic treatment are associâtes with the 5-HT2A receptor polymorphism (102T/C) in Alzheimer’s diseases: a 3-year follow-up longitudinal study. J Alzheim Dis. 2009;17:203–11 (Class C evidence).

    CAS  Google Scholar 

  41. Dombrovski AY, Mulsant BH, Ferrell RE, et al. Serotonin transporter triallelic genotype and response to citalopram and risperidone in dementia with behavioral symptoms. Int Clin Psychopharmacol. 2010;25(1):37–45 (Class B evidence).

    Article  PubMed  Google Scholar 

  42. Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA. 2003;289:210–6 (Class A evidence).

    Article  PubMed  CAS  Google Scholar 

  43. Holmes C, Wilkinson D, Dean C, et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurol. 2004;63:214–9 (Class B evidence).

    CAS  Google Scholar 

  44. Howard RJ, Juszczak E, Ballard C, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med. 2007;357:1382–92 (Class B evidence).

    Article  PubMed  CAS  Google Scholar 

  45. 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 (Class B evidence).

    Article  PubMed  Google Scholar 

  46. 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 randomised, controlled studies. Int J Geriatr Psych. 2005;20:459–64 (Class B evidence).

    Article  CAS  Google Scholar 

  47. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev Issue 2. 2006. Art. No.: CD003154. (Class A evidence).

  48. Gauthier S, Loft H, Cummings J. Improvement in behavioural symptoms in patients with moderate to severe Alzheimer’s disease by memantine: a pooled data analysis. Int J Geriatr Psych. 2008;23:537–45 (Class B evidence).

    Article  CAS  Google Scholar 

  49. Wilcock GK, Ballard CG, Cooper JA, Loft H. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psych. 2008;69:341–8 (Class B evidence).

    Article  CAS  Google Scholar 

  50. Pollock BG, Mulsant BH, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psych. 2002;159:460–5 (Class B evidence).

    Article  Google Scholar 

  51. Pollock BG, Mulsant BH, Rosen J, et al. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. Am J Geriatr Psych. 2007;15:942–52 (Class B evidence).

    Article  Google Scholar 

  52. Finkel SI, Mintzer JE, Dysken M, Krishnan KRR, Burt T, McRae T. 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 Psych. 2004;19:9–18 (Class B evidence).

    Article  Google Scholar 

  53. Teri L, Logsdon RG, Peskind E, et al. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurol. 2000;55:1271–8 (Class B evidence).

    CAS  Google Scholar 

  54. Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psych. 1998;155:54–61 (Class B evidence).

    CAS  Google Scholar 

  55. Olin JT, Fox LS, Pawluczyk S, Taggart NA, Schneider LS. A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. Am J Geriatr Psych. 2001;9:400–5 (Class B evidence).

    CAS  Google Scholar 

  56. Ballard CG, Gauthier S, Cummings JL, et al. Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurosci. 2009;5:245–55 (Class A evidence).

    CAS  Google Scholar 

  57. Konovalov S, Muralee S, Tampi RR. Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review. Int Psychogeriatr. 2008;20:293–308 (Class A evidence).

    Article  PubMed  Google Scholar 

  58. Ballard C, Piggott M, Johnson M, et al. Delusions associated with elevated muscarinic binding in dementia with Lewy bodies. Annals of Neurol. 2000;48:868–76.

    Article  CAS  Google Scholar 

  59. Bodick NC, Offen WW, Levey AI, et al. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol. 1997;54:465–73 (Class B evidence).

    Article  PubMed  CAS  Google Scholar 

  60. Sharp SI, Ballard CG, Chen CP, Francis PT. Aggressive behavior and neuroleptic medication are associated with increased number of alpha1-adrenoceptors in patients with Alzheimer disease. Am J Geriatric Psych. 2007;15:435–7.

    Article  Google Scholar 

  61. Wang LY, Shofer JB, Rohde K, et al. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatr. 2009;17:744–51. (Class B evidence).

    Article  Google Scholar 

  62. www.alzheimers.org.uk/bpsdguide. Accessed 30 Nov 2011.

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Disclosure

Conflicts of Interest: A. Corbett: Consulting fees from Acadia Pharmaceuticals for BPST trial, Speaker’s honoraria from Lundbeck Ltd., Bial Pharmaceuticals, and Novartis; J. Smith: none; B. Creese: none; C. Ballard: Consultancy and speaking fees from Lundbeck, Esai, Bristol-Myers Squibb, Janssen, Acadia, and Novartis pharmaceutical companies; Research support to his institution from Lundbeck and Esai pharmaceutical companies.

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Correspondence to Clive Ballard MB, ChB, MRCPsych, MD.

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Corbett, A., Smith, J., Creese, B. et al. Treatment of Behavioral and Psychological Symptoms of Alzheimer’s Disease. Curr Treat Options Neurol 14, 113–125 (2012). https://doi.org/10.1007/s11940-012-0166-9

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