Skip to main content
NCBI home page
Canadian Family Physician logoLink to Canadian Family Physician
. 2018 May;64(5):369.

Antipsychotics for agitation in dementia

Joey Ton 1, Jamil Ramji 2, G Michael Allan 3
PMCID: PMC5951653  PMID: 29760258

Clinical question

What are the benefits and harms of antipsychotics for agitation in dementia?

Bottom line

Antipsychotics provide little improvement over placebo on agitation scales. However, a 50% improvement in behaviour occurs in about 46% of those taking antipsychotics versus about 33% taking placebo. Harms are serious (eg, 1 increased death in 80 over 3 months) and common. Antipsychotics should be reserved for severe aggression, and withdrawal should be attempted as soon as possible.

Evidence

Evidence includes 6 systematic reviews (5 to 16 RCTs of 856 to 5110 patients that lasted 10 to 12 weeks).1–6 Results are statistically significant unless indicated otherwise.

  • Placebo had large effects (eg, 11-point increase on a 144-point scale—a clinically meaningful difference).7

  • Studies of atypical antipsychotics revealed the following:
    • -Mean improvement on multiple scales was trivial (eg, 3 on a 144-point scale [not likely clinically meaningful]).1–3
    • -Individual antipsychotics had generally similar results.2,5
    • -Some patients attained 50% improvement on scales (eg, 46% with risperidone vs 33% with placebo, number needed to treat [NNT] = 8).4
    • -Harms included stopping owing to adverse events (number needed to harm [NNH] = 13 to 39).2 Serious harms included death (NNH = 77 to 84)1,4 and cerebrovascular events (NNH = 48 to 104).1,2,4
    • -Mini-Mental State Examination score was 0.73 points worse (statistically, not clinically, significant).4
    • -Other harms were somnolence (NNH = 7 to 11), gait abnormalities (NNH = 11 to 20), extrapyramidal symptoms (NNH = 16 to 44), and peripheral edema (NNH = 20 to 25).1,2,4

  • First-generation antipsychotics (eg, haloperidol) appear to have similar rates of harms but inconsistent benefits.6

Context

  • Cholinesterase inhibitors, selective serotonin reuptake inhibitors, trazodone, and valproate provide no meaningful improvement in agitation.8–11
    • -Benzodiazepines might approach antipsychotics in efficacy for agitation but also have harms.12

  • Stopping antipsychotics might reduce death (NNT = 4 at 2 years) with little effect on neuropsychiatric symptoms.13

Implementation

Medical, psychological, and environmental triggers should be assessed and targeted in patients with agitation.14 Pain is a common cause of agitation in dementia, occurring in 57% of patients, and pain resolution can improve agitation.15 A 3 Rs approach (repeat, reassure, redirect) is recommended.14 In severe aggression that threatens the safety of the patient or others, use atypical antipsychotics to target symptoms without sedating the patient.16 The lowest effective dose should be used for the shortest time. A deprescribing algorithm is available.16

Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice@cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

Competing interests

None declared

The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de mai 2018 à la page e232.

References

  • 1.Ma H, Huang Y, Cong Z, Wang Y, Jiang W, Gao S, et al. The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials. J Alzheimers Dis. 2014;42(3):915–37. doi: 10.3233/JAD-140579. [DOI] [PubMed] [Google Scholar]
  • 2.Ballard CG, Waite J, Birks J. Atypical antipsychotics for aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD003476. doi: 10.1002/14651858.CD003476.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Yury CA, Fisher JE. Meta-analysis of the effectiveness of atypical antipsychotics for the treatment of behavioural problems in persons with dementia. Psychother Psychosom. 2007;76(4):213–8. doi: 10.1159/000101499. [DOI] [PubMed] [Google Scholar]
  • 4.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):191–210. doi: 10.1097/01.JGP.0000200589.01396.6d. [DOI] [PubMed] [Google Scholar]
  • 5.Cheung G, Stapelberg J. Quetiapine for the treatment of behavioural and psychological symptoms of dementia (BPSD): a meta-analysis of randomised placebo-controlled trials. N Z Med J. 2011;124(1336):39–50. [PubMed] [Google Scholar]
  • 6.Lonergan E, Luxenberg J, Colford JM, Birks J. Haloperidol for agitation in dementia. Cochrane Database Syst Rev. 2002;(2):CD002852. doi: 10.1002/14651858.CD002852. [DOI] [PubMed] [Google Scholar]
  • 7.Rosenberg PB, Drye LT, Porsteinsson AP, Pollock BG, Devanand DP, Frangakis C, et al. Change in agitation in Alzheimer’s disease in the placebo arm of a nine-week controlled trial. Int Psychogeriatr. 2015;27(12):2059–67. doi: 10.1017/S1041610215001106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Campbell N, Ayub A, Malaz Boustani M, Fox C, Farlow MR, Maidment I, et al. Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: a meta-analysis. Clin Interv Aging. 2008;3(4):719–28. doi: 10.2147/cia.s4250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;(2):CD008191. doi: 10.1002/14651858.CD008191.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.MartinÓn-Torres G, Fioravanti M, Grimley Evans J. Trazodone for agitation in dementia. Cochrane Database Syst Rev. 2004;(3):CD004990. doi: 10.1002/14651858.CD004990. [DOI] [PubMed] [Google Scholar]
  • 11.Lonergan E, Luxenberg J. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev. 2009;(3):CD003945. doi: 10.1002/14651858.CD003945.pub3. [DOI] [PubMed] [Google Scholar]
  • 12.McCracken R, Allan GM. Agitation in dementia – are benzos a backup? Edmonton, AB: Tools for Practice; 2015. [Google Scholar]
  • 13.Allan GM, Behn Smith D. What are the risks of stopping antipsychotics in the elderly? Edmonton, AB: Tools for Practice; 2013. [Google Scholar]
  • 14.Sadowsky CH, Galvin JE. Guidelines for the management of cognitive and behavioral problems in dementia. J Am Board Fam Med. 2012;25(3):350–66. doi: 10.3122/jabfm.2012.03.100183. [DOI] [PubMed] [Google Scholar]
  • 15.Husebo BS, 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. doi: 10.1136/bmj.d4065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Bjerre LM, Farrell B, Hogel M, Graham L, Lemay G, McCarthy L, et al. Deprescribing antipsychotics for behavioural and psychological symptoms of dementia and insomnia. Evidence-based clinical practice guideline. Can Fam Physician. 2018;64:17–27. (Eng), e1–12 (Fr). [PMC free article] [PubMed] [Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

RESOURCES