Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs & Aging
Published in: Drugs & Aging 5/2008

01-05-2008 | Review Article

Alternatives to Atypical Antipsychotics for the Management of Dementia-Related Agitation

Authors: Dr Michael J. Passmore, David M. Gardner, Yvette Polak, Kiran Rabheru

Published in: Drugs & Aging | Issue 5/2008

Login to get access

Abstract

Numerous recent studies have challenged the widely held belief that atypical antipsychotics are safe and effective options for the treatment of behavioural problems such as agitation in patients with dementia. Accordingly, there is a need to reconsider the place of atypical antipsychotics in the treatment of patients with dementia. The present article is intended to assist clinicians with the assessment and pharmacological management of agitation in patients with dementia. We review the risk-benefit evidence for the use of atypical antipsychotics in patients with dementia-related agitation (DRA). Emerging evidence indicates that, for patients with dementia, the risks associated with atypical antipsychotics may outweigh the benefits except for patients with severe agitation who require short-term chemical restraint. We then discuss the importance of a careful assessment to rule out potentially reversible factors contributing to DRA. Finally, we summarize the evidence supporting the use of medications other than antipsychotics to treat DRA. There is wide variability in the levels of evidence supporting the use of nonantipsychotic medication for the treatment of DRA. The best evidence currently exists for cholinesterase inhibitors and serotonin-specific reuptake inhibitor antidepressants. Emerging reports suggest that numerous other medications, for example, antiepileptics, lithium, anxiolytics, analgesics, β-adrenoceptor antagonists, cannabinoid receptor agonists and hormonal agents, may prove to be viable alternatives to antipsychotics for the treatment of severe DRA and more research is urgently needed to help assess the effectiveness of these agents. A comprehensive biopsychosocial assessment and treatment plan is likely the most effective way to manage DRA.
Literature
1.
Public Health Advisory. Deaths with antipsychotics in elderly patients with behavioral disturbances. Rockville (MD): US FDA, 2005 Apr 11
2.
3.
4.
Wooltorton E. Risperidone (Risperdal): increased rate of cerebrovascular events in dementia trials. CMAJ 2002; 167: 1269–70PubMed
5.
Safety alert: Risperdal (risperidone). Washington, DC: US FDA, 2004 Mar 1
6.
Wooltorton E. Olanzapine (Zyprexa): increased incidence of cerebrovascular events in dementia trials. CMAJ 2004; 170(9): 1395PubMedCrossRef
7.
Kryzhanovskaya LA, Jeste DV, Young CA, et al. A review of treatment-emergent adverse events during olanzapine clinical trials in elderly patients with dementia. J Clin Psychiatry 2006; 67(6): 933–45PubMedCrossRef
8.
Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006; 14(3): 191–210PubMed
9.
Liperoti R. Review: atypical antipsychotic drugs slightly increase mortality rates in elderly people with dementia. Evid Based Ment Health 2006; 9(2): 54PubMedCrossRef
10.
Hirsch C. Review: atypical antipsychotic drugs increase risk for death in dementia. ACP J Club 2006; 144(2): 36PubMed
11.
Carson S, McDonagh MS, Peterson K. A systematic review of the efficacy and safety of atypical antipsychotics in patients with psychological and behavioral symptoms of dementia. J Am Geriatr Soc 2006; 54(2): 354–61PubMedCrossRef
12.
van Marum RJ, Jansen PA. Increased risk of stroke during the use of olanzapine or risperidone in patients with dementia. Ned Tijdschr Geneeskd 2005; 149(4): 165–7PubMed
13.
Singh S, Wooltorton E. Increased mortality among elderly patients with dementia using atypical antipsychotics. CMAJ 2005; 173(3): 252PubMedCrossRef
14.
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): 1934–43PubMedCrossRef
15.
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; (1): CD003476
16.
Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci 2006; 7(6): 492–500PubMedCrossRef
17.
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(12): 1708–14PubMedCrossRef
18.
Aarsland D, Perry R, Larsen JP, et al. Neuroleptic sensitivity in Parkinson’s disease and parkinsonian dementias. J Clin Psychiatry 2005; 66(5): 633–7PubMedCrossRef
19.
Pijnenburg YA, Sampson EL, Harvey RJ, et al. Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration. Int J Geriatr Psychiatry 2003; 18(1): 67–72PubMedCrossRef
20.
Suh GH, Shah A. Effect of antipsychotics on mortality in elderly patients with dementia: a 1-year prospective study in a nursing home. Int Psychogeriatr 2005; 17(3): 429–41PubMedCrossRef
21.
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(9): 1090–6PubMedCrossRef
22.
Finkel S, Kozma C, Long S, et al. Risperidone treatment in elderly patients with dementia: relative risk of cerebrovascular events versus other antipsychotics. Int Psychogeriatr 2005; 17(4): 617–29PubMedCrossRef
23.
Moretti R, Torre P, Antonello RM, et al. Olanzapine as a possible treatment of behavioral symptoms in vascular dementia: risks of cerebrovascular events. A controlled, open-label study. J Neurol 2005; 252(10): 1186–93PubMedCrossRef
24.
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(6): 726–30PubMedCrossRef
25.
26.
Smith DA, Beier MT. Association between risperidone treatment and cerebrovascular adverse events: examining the evidence and postulating hypotheses for an underlying mechanism. J Am Med Dir Assoc 2004; 5(2): 129–32PubMedCrossRef
27.
van Iersel MB, Zuidema SU, Koopmans RT, et al. Antipsychotics for behavioural and psychological problems in elderly people with dementia: a systematic review of adverse events. Drugs Aging 2005; 22(10): 845–58PubMedCrossRef
28.
Percudani M, Barbui C, Fortino I, et al. Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly. J Clin Psychopharmacol 2005; 25(5): 468–70PubMedCrossRef
29.
Martin Carrasco M, Ballesteros J, Bulbena A, et al. Effectiveness of typical and atypical neuroleptics in the control of behavioral and psychopathological symptoms of dementia: results of a retrospective study. Actas Esp Psiquiatr 2006; 34(4): 251–6PubMed
30.
Jeste DV, Lacro JP, Bailey A, et al. Lower incidence of tardive dyskinesia with risperidone compared with haloperidol in older patients. J Am Geriatr Soc 1999; 47(6): 716–9PubMed
31.
Schneider LS, Pollock VE, Lyness SA. A meta-analysis of controlled trials of neuroleptic treatment in dementia. J Am Geriatr Soc 1990; 38(5): 553–63PubMed
32.
Kirchner V, Kelly CA, Harvey RJ. Thioridazine for dementia. Cochrane Database Syst Rev 2001; (3): CD000464
33.
Verhey FR, Verkaaik M, Lousberg R. Olanzapine versus haloperidol in the treatment of agitation in elderly patients with dementia: results of a randomized controlled double-blind trial. Dement Geriatr Cogn Disord 2006; 21(1): 1–8PubMedCrossRef
34.
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(5): 509–16PubMed
35.
Herrmann N, Mamdani M, Lanctot KL. Atypical antipsychotics and risk of cerebrovascular accidents. Am J Psychiatry 2004; 161(6): 1113–5PubMedCrossRef
36.
Trifiro G, Verhamme KM, Ziere G, et al. All-cause mortality associated with atypical and typical antipsychotics in demented outpatients. Pharmacoepidemiol Drug Saf 2007; 16(5): 538–44PubMedCrossRef
37.
Gill SS, Rochon PA, Herrmann N, et al. Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ 2005; 330(7489): 445PubMedCrossRef
38.
Schneeweiss S, Setoguchi S, Brookhart A, et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007; 176(5): 627–32PubMedCrossRef
39.
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(22): 2335–41PubMedCrossRef
40.
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(15): 1525–38PubMedCrossRef
41.
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(8): 722–30PubMed
42.
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(7496): 874PubMedCrossRef
43.
Lee PE, Gill SS, Freedman M, et al. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004; 329(7457): 75PubMedCrossRef
44.
Ryder KM, Shorr RI. Review: atypical antipsychotic drugs modestly improve neuropsychiatric symptoms of dementia. ACP J Club 2005; 143(1): 14PubMed
45.
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(6): 497–508PubMedCrossRef
46.
Fischer C, Bozanovic R, Atkins JH, et al. Treatment of delusions in Alzheimer’s disease: response to pharmacotherapy. Dement Geriatr Cogn Disord 2006; 22(3): 260–6PubMedCrossRef
47.
Tariot PN, Profenno LA, Ismail MS. Efficacy of atypical antipsychotics in elderly patients with dementia. J Clin Psychiatry 2004; 65Suppl. 11: 11–5PubMed
48.
Mintzer J, Greenspan A, Caers I, et al. Risperidone in the treatment of psychosis of Alzheimer disease: results from a prospective clinical trial. Am J Geriatr Psychiatry 2006; 14(3): 280–91PubMedCrossRef
49.
De Deyn PP, Buitelaar J. Risperidone in the management of agitation and aggression associated with psychiatric disorders. Eur Psychiatry 2006; 21(1): 21–8PubMedCrossRef
50.
Kurz A, Schwalen SS, Schmitt A. Effects of risperidone on behavioral and psychological symptoms associated with dementia in clinical practice. Int Psychogeriatr 2005; 17(4): 605–16PubMedCrossRef
51.
Frenchman IB. Atypical antipsychotics for nursing home patients: a retrospective chart review. Drugs Aging 2005; 22(3): 257–64PubMedCrossRef
52.
Duran JC, Greenspan A, Diago JI, et al. Evaluation of risperidone in the treatment of behavioral and psychological symptoms and sleep disturbances associated with dementia. Int Psychogeriatr 2005; 17(4): 591–604PubMedCrossRef
53.
Brodaty H, Ames D, Snowdon J, et al. Risperidone for psychosis of Alzheimer’s disease and mixed dementia: results of a double-blind, placebo-controlled trial. Int J Geriatr Psychiatry 2005; 20(12): 1153–7PubMedCrossRef
54.
Arriola E, Ignacio Diago J, et al. Open-label, observational study of the effects of risperidone on the behavioral and psychological symptoms of dementia and caregiver stress in the community setting. Am J Geriatr Pharmacother 2005; 3(1): 8–16PubMedCrossRef
55.
Wancata J. Efficacy of risperidone for treating patients with behavioral and psychological symptoms of dementia. Int Psychogeriatr 2004; 16(1): 107–15PubMedCrossRef
56.
Meguro K, Meguro M, Tanaka Y, et al. Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer’s disease. J Geriatr Psychiatry Neurol 2004; 17(2): 61–7PubMedCrossRef
57.
Rabinowitz J, Katz IR, De Deyn PP, et al. Behavioral and psychological symptoms in patients with dementia as a target for pharmacotherapy with risperidone. J Clin Psychiatry 2004; 65(10): 1329–34PubMedCrossRef
58.
DeVane CL, Mintzer J. Risperidone in the management of psychiatric and neurodegenerative disease in the elderly: an update. Psychopharmacol Bull 2003; 37(4): 116–32PubMed
59.
Zaudig M. A risk-benefit assessment of risperidone for the treatment of behavioural and psychological symptoms in dementia. Drug Saf 2000; 23(3): 183–95PubMedCrossRef
60.
Negron AE, Reichman WE. Risperidone in the treatment of patients with Alzheimer’s disease with negative symptoms. Int Psychogeriatr 2000; 12(4): 527–36PubMedCrossRef
61.
Lavretsky H, Sultzer D. A structured trial of risperidone for the treatment of agitation in dementia. Am J Geriatr Psychiatry 1998; 6(2): 127–35PubMed
62.
Herrmann N, Rivard MF, Flynn M, et al. Risperidone for the treatment of behavioral disturbances in dementia: a case series. J Neuropsychiatry Clin Neurosci 1998; 10(2): 220–3PubMed
63.
Kopala LC, Honer WG. The use of risperidone in severely demented patients with persistent vocalizations. Int J Geriatr Psychiatry 1997; 12(1): 73–7PubMedCrossRef
64.
Laks J, Engelhardt E, Marinho V, et al. Efficacy and safety of risperidone oral solution in agitation associated with dementia in the elderly. Arq Neuropsiquiatr 2001; 59(4): 859–64PubMedCrossRef
65.
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(2): 134–43PubMedCrossRef
66.
Rainer MK, Masching AJ, Ertl MG, et al. Effect of risperidone on behavioral and psychological symptoms and cognitive function in dementia. J Clin Psychiatry 2001; 62(11): 894–900PubMedCrossRef
67.
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. Risperidone Study Group. J Clin Psychiatry 1999; 60(2): 107–15PubMedCrossRef
68.
Rocca P, Marino F, Montemagni C, et al. Risperidone, olanzapine and quetiapine in the treatment of behavioral and psychological symptoms in patients with Alzheimer’s disease: preliminary findings from a naturalistic, retrospective study. Psychiatry Clin Neurosci 2007; 61(6): 622–9PubMedCrossRef
69.
Schatz RA. Olanzapine for psychotic and behavioral disturbances in Alzheimer disease. Ann Pharmacother 2003; 37(9): 1321–4PubMedCrossRef
70.
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(1): 34–40PubMedCrossRef
71.
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, placebo-controlled trial. The HGEU Study Group. Arch Gen Psychiatry 2000; 57(10): 968–76PubMedCrossRef
72.
Edell WS, Tunis SL. Antipsychotic treatment of behavioral and psychological symptoms of dementia in geropsychiatric inpatients. Am J Geriatr Psychiatry 2001; 9(3): 289–97PubMed
73.
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(4): 201–4PubMedCrossRef
74.
Tariot PN, Ismail MS. Use of quetiapine in elderly patients. J Clin Psychiatry 2002; 63Suppl. 13: 21–6PubMed
75.
Scharre DW, Chang SI. Cognitive and behavioral effects of quetiapine in Alzheimer disease patients. Alzheimer Dis Assoc Disord 2002; 16(2): 128–30PubMedCrossRef
76.
MacKnight C, Rojas-Fernandez C. Quetiapine for sexually inappropriate behavior in dementia [letter]. J Am Geriatr Soc 2000; 48(6): 707PubMed
77.
Madhusoodanan S, Bogunovic O. Switching elderly patients with dementia from risperidone to quetiapine: a retrospective study. Am J Alzheimers Dis Other Demen 2006; 21(3): 169–74PubMedCrossRef
78.
Zhong KX, Tariot PN, Mintzer J, et al. Quetiapine to treat agitation in dementia: a randomized, double-blind, placebo-controlled study. Curr Alzheimer Res 2007; 4(1): 81–93PubMedCrossRef
79.
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(11): 918–31PubMedCrossRef
80.
Laks J, Miotto R, Marinho V, et al. Use of aripiprazole for psychosis and agitation in dementia. Int Psychogeriatr 2006; 18(2): 335–40PubMedCrossRef
81.
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(5): 463–7PubMedCrossRef
82.
Lee HB, Hanner JA, Yokley JL, et al. Clozapine for treatmentresistant agitation in dementia. J Geriatr Psychiatry Neurol 2007; 20(3): 178–82PubMedCrossRef
83.
Mauri M, Mancioli A, Rebecchi V, et al. Amisulpride in the treatment of behavioural disturbances among patients with moderate to severe Alzheimer’s disease. Acta Neurol Scand 2006; 114(2): 97–101PubMedCrossRef
84.
Cole SA, Saleem R, Shea WP, et al. Ziprasidone for agitation or psychosis in dementia: four cases. Int J Psychiatry Med 2005; 35(1): 91–8PubMedCrossRef
85.
Rainer MK, Mucke HA, Kruger-Rainer C, et al. Zotepine for behavioural and psychological symptoms in dementia: an open-label study. CNS Drugs 2004; 18(1): 49–55PubMedCrossRef
86.
Allain H, Dautzenberg PH, Maurer K, et al. Double blind study of tiapride versus haloperidol and placebo in agitation and aggressiveness in elderly patients with cognitive impairment. Psychopharmacology (Berl) 2000; 148(4): 361–6CrossRef
87.
Cummings JL, Street J, Masterman D, et al. Efficacy of olanzapine in the treatment of psychosis in dementia with Lewy bodies. Dement Geriatr Cogn Disord 2002; 13(2): 67–73PubMedCrossRef
88.
Fernandez HH, Trieschmann ME, Burke MA, et al. Quetiapine for psychosis in Parkinson’s disease versus dementia with Lewy bodies. J Clin Psychiatry 2002; 63(6): 513–5PubMedCrossRef
89.
Rabheru K. BVS tool. In: Donnelly M, editor. Canadian Academy of Geriatric Psychiatry E-newsletter. 1st ed. Toronto (ON): CAGP, 2005
90.
Rabheru K. Take a S-M-A-R-T approach: unpredictable course of dementia symptoms can be managed. Can Fam Physician 2003; 49: 389
91.
Mintzer JE, Brawman-Mintzer O. Agitation as a possible expression of generalized anxiety disorder in demented elderly patients: toward a treatment approach. J Clin Psychiatry 1996; 57Suppl. 7: 55–63; discussion 73–5PubMed
92.
Cummings JL. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry 2003; 11(2): 131–45PubMed
93.
Franco KN, Messinger-Rapport B. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. J Am Med Dir Assoc 2006; 7(3): 201–2PubMedCrossRef
94.
Wynn ZJ, Cummings JL. Cholinesterase inhibitor therapies and neuropsychiatric manifestations of Alzheimer’s disease. Dement Geriatr Cogn Disord 2004; 17(1–2): 100–8PubMedCrossRef
95.
Herrmann N, Rabheru K, Wang J, et al. Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials. Am J Geriatr Psychiatry 2005; 13(6): 527–34PubMed
96.
Cummings JL, Koumaras B, Chen M, et al. Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer’s disease: a 26-week, multicenter, open-label study. Am J Geriatr Pharmacother 2005; 3(3): 137–48PubMedCrossRef
97.
Figiel G, Sadowsky C. A systematic review of the effectiveness of rivastigmine for the treatment of behavioral disturbances in dementia and other neurological disorders. Curr Med Res Opin 2008; 24(1): 157–66PubMedCrossRef
98.
Cummings JL, McRae T, Zhang R; Donepezil-Sertraline Study Group. Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioural disorders. Am J Geriatr Psychiatry 2006; 14(7): 605–12PubMedCrossRef
99.
Barak Y, Bodner E, Zemishlani H, et al. Donepezil for the treatment of behavioral disturbances in Alzheimer’s disease: a 6-month open trial. Arch Gerontol Geriatr 2001; 33(3): 237–41PubMedCrossRef
100.
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(6): 313–7PubMedCrossRef
101.
Mega MS, Masterman DM, O’Connor SM, et al. The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease. Arch Neurol 1999; 56(11): 1388–93PubMedCrossRef
102.
Howard RJ, Juszczak E, Ballard CG, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med 2007; 357(14): 1382–92PubMedCrossRef
103.
Rockwood K, Black SE, Robillard A, et al. Potential treatment effects of donepezil not detected in Alzheimer’s disease clinical trials: a physician survey. Int J Geriatr Psychiatry 2004; 19(10): 954–60PubMedCrossRef
104.
Alagiakrishnan K, Sclater A, Robertson D. Role of cholinesterase inhibitor in the management of sexual aggression in an elderly demented woman [letter]. J Am Geriatr Soc 2003; 51(9): 1326PubMed
105.
Rosin RA, Levine MD, Peskind E. Transdermal nicotine for agitation in dementia. Am J Geriatr Psychiatry 2001; 9(4): 443–4PubMed
106.
Holm AC. Alleviation of multiple abnormalities by galantamine treatment in two patients with dementia with Lewy bodies. Am J Alzheimers Dis Other Demen 2004; 19(4): 215–8PubMedCrossRef
107.
Maclean LE, Collins CC, Byrne EJ. Dementia with Lewy bodies treated with rivastigmine: effects on cognition, neuropsychiatric symptoms, and sleep. Int Psychogeriatr 2001; 13(3): 277–88PubMedCrossRef
108.
McKeith IG, Grace JB, Walker Z, et al. Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial. Int J Geriatr Psychiatry 2000; 15(5): 387–92PubMedCrossRef
109.
Bullock R, Cameron A. Rivastigmine for the treatment of dementia and visual hallucinations associated with Parkinson’s disease: a case series. Curr Med Res Opin 2002; 18(5): 258–64PubMedCrossRef
110.
Suh DC, Arcona S, Thomas SK, et al. Risk of antipsychotic drug use in patients with Alzheimer’s disease treated with rivastigmine. Drugs Aging 2004; 21(6): 395–403PubMedCrossRef
111.
Bullock R. Efficacy and safety of memantine in moderate-to-severe Alzheimer disease: the evidence to date. Alzheimer Dis Assoc Disord 2006; 20(1): 23–9PubMedCrossRef
112.
Cummings JL, Schneider E, Tariot PN, et al. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 2006; 67(1): 57–63PubMedCrossRef
113.
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 Psychiatry 2005; 20(5): 459–64PubMedCrossRef
114.
Livingston G, Katona C. The place of memantine in the treatment of Alzheimer’s disease: a number needed to treat analysis. Int J Geriatr Psychiatry 2004; 19(10): 919–25PubMedCrossRef
115.
McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev 2006; (2): CD003154
116.
Sleeper RB. Antipsychotic dose-sparing effect with addition of memantine. Ann Pharmacother 2005; 39(9): 1573–6PubMedCrossRef
117.
Monastere R, Camarda C, Pipia C, et al. Visual hallucinations and agitation in Alzheimer’s disease due to memantine: report of three cases [letter]. J Neurol Neurosurg Psychiatry 2007; 78(5): 546CrossRef
118.
Ridha BH, Josephs KA, Rossor MN. Delusions and hallucinations in dementia with Lewy bodies: worsening with memantine. Neurology 2005; 65(3): 481–2PubMedCrossRef
119.
Menendez-Gonzalez M, Calatayud MT, Blazquez-Menes B. Exacerbation of Lewy bodies dementia due to memantine. J Alzheimers Dis 2005; 8(3): 289–91PubMed
120.
Schneider LS, Severson JA, Chui HC, et al. Platelet tritiated imipramine binding and MAO activity in Alzheimer’s disease patients with agitation and delusions. Psychiatry Res 1988; 25(3): 311–22PubMedCrossRef
121.
Senanarong V, Cummings JL, Fairbanks L, et al. Agitation in Alzheimer’s disease is a manifestation of frontal lobe dysfunction. Dement Geriatr Cogn Disord 2004; 17(1–2): 14–20PubMedCrossRef
122.
Roth BL, Hanizavareh SM, Blum AE. Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders. Psycho-pharmacology (Berl) 2004; 174(1): 17–24
123.
Scharre DW, Davis RA, Warner JL, et al. A pilot open-label trial of citalopram for restless activity and aberrant motor behaviors in Alzheimer disease. Am J Geriatr Psychiatry 2003; 11(6): 687–91PubMed
124.
Kim KY, Bader GM, Jones E. Citalopram for verbal agitation in patients with dementia. J Geriatr Psychiatry Neurol 2000; 13(2): 53–5PubMedCrossRef
125.
Pollock BG, Mulsant BH, Sweet R, et al. An open pilot study of citalopram for behavioral disturbances of dementia: plasma levels and real-time observations. Am J Geriatr Psychiatry 1997; 5(1): 70–8PubMed
126.
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 Psychiatry 2007; 15(11): 942–52PubMedCrossRef
127.
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 Psychiatry 2002; 159(3): 460–5PubMedCrossRef
128.
Lanctot KL, Herrmann N, van Reekum R, et al. Gender, aggression and serotonergic function are associated with response to sertraline for behavioral disturbances in Alzheimer’s disease. Int J Geriatr Psychiatry 2002; 17(6): 531–41PubMedCrossRef
129.
Kitamura Y, Kudo Y, Imamura T. Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease: a retrospective study focused on the aggression and negativism in caregiving situations. No To Shinkei 2006; 58(6): 483–8PubMed
130.
Lebert F, Stekke W, Hasenbroekx C, et al. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004; 17(4): 355–9PubMedCrossRef
131.
Sultzer DL, Gray KF, Gunay I, et al. A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. Am J Geriatr Psychiatry 1997; 5(1): 60–9PubMed
132.
Martinon-Torres G, Fioravanti M, Grimley EJ. Trazodone for agitation in dementia. Cochrane Database Syst Rev 2004; (4): CD004990
133.
Teri L, Logsdon RG, Peskind E, et al. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology 2000; 55(9): 1271–8PubMedCrossRef
134.
McDonald WM, Thompson TR. Treatment of mania in dementia with electroconvulsive therapy. Psychopharmacol Bull 2001; 35(2): 72–82PubMed
135.
Arrsland D, Odberg S. Electroconvulsive therapy of depression in Alzheimer’s disease: a case presentation of acute and maintenance electroconvulsive therapy. Nord J Psychiatry 1996; 50(2): 169–73CrossRef
136.
Price TR, McAllister TW. Safety and efficacy of ECT in depressed patients with dementia: a review of clinical experience. Convuls Ther 1989; 5(1): 61–74PubMed
137.
Rao V, Lyketsos CG. The benefits and risks of ECT for patients with primary dementia who also suffer from depression. Int J Geriatr Psychiatry 2000; 15(8): 729–35PubMedCrossRef
138.
Kunik ME, Puryear L, Orengo CA, et al. The efficacy and tolerability of divalproex sodium in elderly demented patients with behavioral disturbances. Int J Geriatr Psychiatry 1998; 13(1): 29–34PubMedCrossRef
139.
Meinhold JM, Blake LM, Mini LJ, et al. Effect of divalproex sodium on behavioural and cognitive problems in elderly dementia. Drugs Aging 2005; 22(7): 615–26PubMedCrossRef
140.
Narayan M, Nelson JC. Treatment of dementia with behavioral disturbance using divalproex or a combination of divalproex and a neuroleptic. J Clin Psychiatry 1997; 58(8): 351–4PubMedCrossRef
141.
Lott AD, McElroy SL, Keys MA. Valproate in the treatment of behavioral agitation in elderly patients with dementia. J Neuropsychiatry Clin Neurosci 1995; 7(3): 314–9PubMed
142.
Porsteinsson AP, Tariot PN, Jakimovich LJ, et al. Valproate therapy for agitation in dementia: open-label extension of a double-blind trial. Am J Geriatr Psychiatry 2003; 11(4): 434–40PubMed
143.
Forester B, Vanelli M, Hyde J, et al. Report on an open-label prospective study of divalproex sodium for the behavioral and psychological symptoms of dementia as monotherapy and in combination with second-generation antipsychotic medication. Am J Geriatr Pharmacother 2007; 5(3): 209–17PubMedCrossRef
144.
Tariot PN, Raman R, Jakimovich L, et al. Divalproex sodium in nursing home residents with possible or probable Alzheimer disease complicated by agitation: a randomized, controlled trial. Am J Geriatr Psychiatry 2005; 13(11): 942–9PubMed
145.
Lonergan ET, Cameron M, Luxenberg J. Valproic acid for agitation in dementia. Cochrane Database Syst Rev 2004; (2): CD003945
146.
Profenno LA, Jakimovich L, Holt CJ, et al. A randomized, double-blind, placebo-controlled pilot trial of safety and tolerability of two doses of divalproex sodium in outpatients with probable Alzheimer’s disease. Curr Alzheimer Res 2005; 2(5): 553–8PubMedCrossRef
147.
Olin JT, Fox LS, Pawluczyk S, et al. A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. Am J Geriatr Psychiatry 2001; 9(4): 400–5PubMed
148.
Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry 1998; 155(1): 54–61PubMed
149.
Tariot PN, Jakimovich LJ, Erb R, et al. Withdrawal from controlled carbamazepine therapy followed by further carbamazepine treatment in patients with dementia. J Clin Psychiatry 1999; 60(10): 684–9PubMedCrossRef
150.
Tariot PN, Erb R, Leibovici A, et al. Carbamazepine treatment of agitation in nursing home patients with dementia: a preliminary study. J Am Geriatr Soc 1994; 42(11): 1160–6PubMed
151.
Freymann N, Michael R, Dodel R, et al. Successful treatment of sexual disinhibition in dementia with carbamazepine: a case report. Pharmacopsychiatry 2005; 38(3): 144–5PubMedCrossRef
152.
Lemke MR. Effect of carbamazepine on agitation in Alzheimer’s inpatients refractory to neuroleptics. J Clin Psychiatry 1995; 56(8): 354–7PubMed
153.
Gleason RP, Schneider LS. Carbamazepine treatment of agitation in Alzheimer’s outpatients refractory to neuroleptics. J Clin Psychiatry 1990; 51(3): 115–8PubMed
154.
Moretti R, Torre P, Antonello RM, et al. Gabapentin for the treatment of behavioural alterations in dementia: preliminary 15-month investigation. Drugs Aging 2003; 20(14): 1035–40PubMedCrossRef
155.
Fhager B, Meiri IM, Sjogren M, et al. Treatment of aggressive behavior in dementia with the anticonvulsant topiramate: a retrospective pilot study. Int Psychogeriatr 2003; 15(3): 307–9PubMedCrossRef
156.
Jacobson SA, Pies RW, Katz IR. Clinical manual of geriatric psychopharmacology. Washington, DC: American Psychiatric Publishing, 2007
157.
Fava M. Psychopharmacologic treatment of pathologic aggression. Psychiatr Clin North Am 1997; 20(2): 427–51PubMedCrossRef
158.
Smith DA, Perry PJ. Nonneuroleptic treatment of disruptive behavior in organic mental syndromes. Ann Pharmacother 1992; 26(11): 1400–8PubMed
159.
Chuang DM. Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? Crit Rev Neurobiol 2004; 16(1–2): 83–90PubMedCrossRef
160.
Dunn N, Holmes C, Mullee M. Does lithium therapy protect against the onset of dementia? Alzheimer Dis Assoc Disord 2005; 19(1): 20–2PubMedCrossRef
161.
Holton A, George K. The use of lithium in severely demented patients with behavioural disturbance. Br J Psychiatry 1985; 146: 99–100PubMed
162.
Kunik ME, Yudofsky SC, Silver JM, et al. Pharmacologic approach to management of agitation associated with dementia. J Clin Psychiatry 1994; 55 Suppl.: 13–7PubMed
163.
Twelftree H, Qazi A. Relationship between anxiety and agitation in dementia. Aging Ment Health 2006; 10(4): 362–7PubMedCrossRef
164.
Christensen DB, Benfield WR. Alprazolam as an alternative to low-dose haloperidol in older, cognitively impaired nursing facility patients. J Am Geriatr Soc 1998; 46(5): 620–5PubMed
165.
Colenda 3rd CC. Buspirone in treatment of agitated demented patient [letter]. Lancet 1988; I(8595): 1169CrossRef
166.
Cooper JP. Buspirone for anxiety and agitation in dementia [letter]. J Psychiatry Neurosci 2003; 28(6): 469PubMed
167.
Sato S, Mizukami K, Asada T. A preliminary open-label study of 5-HT1A partial agonist tandospirone for behavioural and psychological symptoms associated with dementia. Int J Neuropsychopharmacol 2007; 10(2): 281–3PubMedCrossRef
168.
Zieber CG, Hagen B, Armstrong-Esther C, et al. Pain and agitation in long-term care residents with dementia: use of the Pittsburgh Agitation Scale. Int J Palliat Nurs 2005; 11(2): 71–8PubMed
169.
Villanueva MR, Smith TL, Erickson JS, et al. Pain Assessment for the Dementing Elderly (PADE): reliability and validity of a new measure. J Am Med Dir Assoc 2003; 4(1): 1–8PubMedCrossRef
170.
Gilron I, Watson CP, Cahill CM, et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3): 265–75PubMedCrossRef
171.
Bascunana H, Villarreal I, Alfonso S, et al. Agitation in head injury: II. Treatment with antidepressant, sympathomimetic, beta blocker, dopaminergic and other drugs. Rev Neurol 2000; 30(11): 1044–7PubMed
172.
Summers WK. The management of agitation in demented patients with propranolol. J Alzheimers Dis 2006; 9(1): 69–75PubMed
173.
Pauszek ME. Propranolol for treatment of agitation in senile dementia. Indiana Med 1991; 84(1): 16–7PubMed
174.
Herrmann N, Lanctot KL, Eryavec G, et al. Noradrenergic activity is associated with response to pindolol in aggressive Alzheimer’s disease patients. J Psychopharmacol 2004; 18(2): 215–20PubMedCrossRef
175.
176.
Witkin JM, Tzavara ET, Nomikos GG. A role for cannabinoid CB1 receptors in mood and anxiety disorders. Behav Pharmacol 2005; 16(5–6): 315–31PubMedCrossRef
177.
Porter AC, Felder CC. The endocannabinoid nervous system: unique opportunities for therapeutic intervention. Pharmacol Ther 2001; 90(1): 45–60PubMedCrossRef
178.
Woolridge E, Barton S, Samuel J, et al. Cannabis use in HIV for pain and other medical symptoms. J Pain Symptom Manage 2005; 29(4): 358–67PubMedCrossRef
179.
Eubanks LM, Rogers CJ, Beuscher 4th AE, et al. A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol Pharm 2006; 3(6): 773–7PubMedCrossRef
180.
Ramirez BG, Blazquez C, Gomez del Pulgar T, et al. Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 2005; 25(8): 1904–13PubMedCrossRef
181.
Pazos MR, Nunez E, Benito C, et al. Role of the endocannabinoid system in Alzheimer’s disease: new perspectives. Life Sci 2004; 75(16): 1907–15PubMedCrossRef
182.
Volicer L, Stelly M, Morris J, et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 1997; 12(9): 913–9PubMedCrossRef
183.
Walther S, Mahlberg R, Eichmann U, et al. Delta-9-tetrahydrocannabinol for night-time agitation in severe dementia. Psychopharmacology (Berl) 2006; 185(4): 524–8CrossRef
184.
Passmore MJ. The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation. Int J Geriatr Psychiatry 2008; 23(1): 116–7PubMedCrossRef
185.
Amadeo M. Antiandrogen treatment of aggressivity in men suffering from dementia. J Geriatr Psychiatry Neurol 1996; 9(3): 142–5PubMed
186.
Shelton PS, Brooks VG. Estrogen for dementia-related aggression in elderly men. Ann Pharmacother 1999; 33(7–8): 808–12PubMedCrossRef
187.
Rosin RA, Raskind MA. Gonadotrophin-releasing hormone agonist treatment of aggression in Alzheimer’s disease: a case report. Int Psychogeriatr 2005; 17(2): 313–8PubMedCrossRef
188.
Cohen-Mansfield J, Garfinkel D, Lipson S. Melatonin for treatment of sundowning in elderly persons with dementia: a preliminary study. Arch Gerontol Geriatr 2000; 31(1): 65–76PubMedCrossRef
189.
Cardinali DP, Brusco LI, Liberczuk C, et al. The use of melatonin in Alzheimer’s disease. Neuro Endocrinol Lett 2002; 23Suppl. 1: 20–3PubMed
190.
Mahlberg R, Kunz D, Sutej I, et al. Melatonin treatment of day-night rhythm disturbances and sundowning in Alzheimer disease: an open-label pilot study using actigraphy. J Clin Psychopharmacol 2004; 24(4): 456–9PubMedCrossRef
Metadata
Title
Alternatives to Atypical Antipsychotics for the Management of Dementia-Related Agitation
Authors
Dr Michael J. Passmore
David M. Gardner
Yvette Polak
Kiran Rabheru
Publication date
01-05-2008
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 5/2008
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.2165/00002512-200825050-00003

Other articles of this Issue 5/2008

Drugs & Aging 5/2008 Go to the issue

Review Article

Potential Adverse Effects of Bronchodilators in the Treatment of Airways Obstruction in Older People

Therapy In Practice

Asymptomatic Hyperthyroidism in Older Adults

Review Article

Surgical Site Infections in Older Adults

Current Opinion

Androgen Deficiency as a Predictor of Metabolic Syndrome in Aging Men
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits