518
Views
1
CrossRef citations to date
0
Altmetric
Review

The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer’s disease

, , &
Pages 461-467 | Received 30 Jan 2018, Accepted 10 May 2018, Published online: 21 May 2018

References

  • Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA. 2002;288:1475–1483.
  • Wergeland JN, Selbæk G, Bergh S, et al. Predictors for nursing home admission and death among community-dwelling people 70 years and older who receive domiciliary care. Dement Geriatr Cogn Dis Extra. 2015;5:320–329.
  • Shin I-S, Carter M, Masterman D, et al. Neuropsychiatric symptoms and quality of life in Alzheimer disease. Am J Geriatr Psychiatry. 2005;13:469–474.
  • Wilkosz PA, Seltman HJ, Devlin B, et al. Trajectories of cognitive decline in Alzheimer’s disease. Int Psychogeriatr. 2010;22:281–290.
  • Sultana J, Fontana A, Giorgianni F, et al. The effect of safety warnings on antipsychotic drug prescribing in elderly persons with dementia in the United Kingdom and Italy: a population-based study. CNS Drugs. 2016;30:1097–1109.
  • Ballard C, Creese B, Corbett A, et al. Atypical antipsychotics for the treatment of behavioral and psychological symptoms in dementia, with a particular focus on longer term outcomes and mortality. Expert Opin Drug Saf. 2011;10:35–43.
  • 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;14:191–210.
  • Ballard CG, Waite J, Birks J. Atypical antipsychotics for aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev. 2006.
  • Patel AN, Lee S, Andrews HF, et al. Prediction of relapse after discontinuation of antipsychotic treatment in Alzheimer’s disease: the role of hallucinations. Am J Psychiatry. 2017;174:362–369.
  • Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neurosci. 2006;7:492.
  • Murray PS, Kumar S, Maa D-S, et al. Psychosis in Alzheimer’s disease. Biol Psychiatry. 2014;75:542–552.
  • 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
  • Bruen PD, McGeown WJ, Shanks MF, et al. Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer’s disease. Brain. 2008;131:2455–2463.
  • Garcia-Alloza M, Gil-Bea FJ, Diez-Ariza M, et al. Cholinergic–serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease. Neuropsychologia. 2005;43:442–449.
  • Garcia-Alloza M, Hirst WD, Chen CPLH, et al. Differential involvement of 5-ht1b/1d and 5-ht6 receptors in cognitive and non-cognitive symptoms in Alzheimer’s disease. Neuropsychopharmacology. 2003;29:410.
  • Tekin S, Mega MS, Masterman DM, et al. Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease. Ann Neurol. 2001;49:355–361.
  • Zubenko GS, Moossy J, Martinez A, et al. Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch Neurol. 1991;48:619–624.
  • Farber NB, Rubin EH, Newcomer JW, et al. Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry. 2000;57:1165–1173.
  • Sweet RA, Hamilton RL, Lopez OL, et al. Psychotic symptoms in Alzheimer’s disease are not associated with more severe neuropathologic features. Int Psychogeriatr. 2000;12:547–558.
  • Murray PS, Kirkwood CM, Ikonomovic MD, et al. Tau phosphorylation is exaggerated in Alzheimer disease with psychosis. Am J Geriatr Psychiatry. 2013;21:S80–S1.
  • Koppel J, Acker C, Davies P, et al. Psychotic Alzheimer’s disease is associated with gender-specific tau phosphorylation abnormalities. Neurobiol Aging. 2014;35:2021–2028.
  • Ballard C, Corbett A, Chitramohan R, et al. Management of agitation and aggression associated with Alzheimer’s disease: controversies and possible solutions. Curr Opin Psych. 2009;22:532–540.
  • Ballard C, Orrell M, Yongzhong S, et al. Impact of antipsychotic review and nonpharmacological intervention on antipsychotic use, neuropsychiatric symptoms, and mortality in people with dementia living in nursing homes: a factorial cluster-randomized controlled trial by the well-being and health for people with dementia (WHELD) program. Am J Psychiatry. 2016;173:252–262.
  • 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.
  • Rovner BW, Steele CD, Shmuely Y, et al. A randomized trial of dementia care in nursing homes. J Am Geriatr Soc. 1996;44:7–13.
  • Ballard C, Corbett A, Orrell M, et al. Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial. Plos Med. 2018;15:e1002500.
  • Surr CA, Walwyn REA, Lilley-Kelly A, et al. Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial. Trials. 2016;17:300.
  • Trinh NH, Hoblyn J, Mohanty S, et al. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA. 2003;289:210–216.
  • 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.
  • Howard RJ, Juszczak E, Ballard CG, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med. 2007;357:1382–1392.
  • Mckeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000;356:2031–2036.
  • Wilcock GK, Ballard CG, Cooper JA, et al. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psychiatry. 2008;69:341–348.
  • 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 Psychiatry. 2008;23:537–545.
  • Fox C, Crugel M, Maidment I, et al. Efficacy of memantine for agitation in Alzheimer’s dementia: a randomised double-blind placebo controlled trial. PLoS One. 2012;7:e35185.
  • Ballard C, Thomas A, Gerry S, et al. A double-blind randomized placebo-controlled withdrawal trial comparing memantine and antipsychotics for the long-term treatment of function and neuropsychiatric symptoms in people with Alzheimer’s disease (MAIN-AD). J Am Med Dir Assoc. 2015;16:316–322.
  • Bodick NC, Offen WW, Shannon HE, et al. The selective muscarinic agonist xanomeline improves both the cognitive deficits and behavioral symptoms of Alzheimer disease. Alzheimer Dis Assoc Disord. 1997;11(Suppl 4):S16–22.
  • Kavoussi R, Miller A, Breier A, et al. Results of a double-blind, placebo-controlled, tolerability study of karxt: a novel combination targeting muscarinic acetylcholine receptors using xanomeline with tropsium chloride to mitigate cholinergic side effects. In:American society of clinical psychopharmacology,Eds, 2017;‘ Florida.
  • 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.
  • 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;159:460–465.
  • Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the citad randomized clinical trial. JAMA. 2014;311:682–691.
  • Cakir S, Kulaksizoglu IB. The efficacy of mirtazapine in agitated patients with Alzheimer’s disease: a 12-week open-label pilot study. Neuropsychiatr Dis Treat. 2008;4:963–966.
  • We R, Coleman J, Aupperle P et al. An open label pilot study of mirtazapine for the treatment of dementia-associated behavioral problems. In: International Psychogeriatric Association Eleventh International Congress. Ed.(Eds) Chicago, 2003.
  • Banerjee S, Hellier J, Romeo R, et al. Study of the use of antidepressants for depression in dementia: the HTA-SADD trial–a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine. Health Technol Assess. 2013;17:1–166.
  • Teri L, Logsdon RG, Peskind E, et al. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology. 2000;55:1271–1278.
  • 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;5:60–69.
  • Sommer OH, Aga O, Cvancarova M, et al. Effect of oxcarbazepine in the treatment of agitation and aggression in severe dementia. Dement Geriatr Cogn Disord. 2009;27:155–163.
  • Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry. 1998;155:54–61.
  • 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;9:400–405.
  • Tariot PN, Schneider LS, Cummings J, et al. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch Gen Psychiatry. 2011;68:853–861.
  • Husebo BS, Ballard C, Sandvik R, et al. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343:d4065.
  • Rajkumar AP, Ballard C, Fossey J, et al. Epidemiology of pain in people with dementia living in care homes: longitudinal course, prevalence, and treatment implications. J Am Med Dir Assoc. 2017;18:453.e1-.e6.
  • Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. The Lancet. 2014;383:533–540.
  • Ballard C, Banister C, Khan Z, et al. Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer’s disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study. Lancet Neurol. 2018;17:213–222.
  • Er P, Ma R, Wang L Two pilot studies of the alpha-1 adrenoreceptor antagonist prazosin for agitation/aggression in AD lead to an Alzheimer’s disease cooperative study multicenter trial. In: Alzheimer’s Association International Conference. (Ed.(Eds) Copenhagen, 2014; P821.
  • Walther S, Schupbach B, Seifritz E, et al. Randomized, controlled crossover trial of dronabinol, 2.5 mg, for agitation in 2 patients with dementia. J Clin Psychopharmacol. 2011;31:256–258.
  • Walther S, Mahlberg R, Eichmann U, et al. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology (Berl). 2006;185:524–528.
  • Mahlberg R, Walther S. Actigraphy in agitated patients with dementia Monitoring Treatment Outcomes. . Z Gerontol Geriatr. 2007;40:178–184.
  • Passmore MJ. The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation. Int J Geriatr Psychiatry. 2008;23:116–117.
  • Woodward MR, Harper DG, Stolyar A, et al. Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. Am J Geriatr Psychiatry. 2014;22:415–419.
  • Cummings JL, Lyketsos CG, Peskind ER, et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA. 2015;314:1242–1254.
  • Maa D-S, Weamer EA, Klei L, et al. Genetic risk for schizophrenia and psychosis in Alzheimer disease. Mol Psychiatry 2018;23:963.
  • Carter R. ffytche DH. On visual hallucinations and cortical networks: a trans-diagnostic review. J Neurol. 2015;262:1780–1790.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.