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Antipsychotics in dementia

Drug-class library

Antipsychotics in dementia carry a boxed warning, a randomized mortality signal, and a set of situations in which they remain the right answer. Holding all three at once is the whole task.

Before you read on

Never stop or change a prescribed medication without speaking to your own prescriber. Several of the classes described on this site rebound, or cause a withdrawal syndrome, when they are stopped abruptly, and some have to be reduced gradually over weeks or months under supervision. Nothing here is advice about your own medication, and nothing here is a reason to change anything on your own.

The evidence in brief

The detailed treatment of the mortality signal, the withdrawal trials, and who relapses is on a dedicated page: Antipsychotics and mortality in dementia. What follows is what a review of this class involves.

  • The risk of death is real and it is small in absolute terms. The pivotal meta-analysis of 15 randomized placebo-controlled trials found deaths in 3.5% on drug against 2.3% on placebo — odds ratio 1.54 (95% CI 1.06 to 2.23), risk difference 0.01 — over ten to twelve weeks.
  • The benefit is also small. A Cochrane review of 24 randomized trials and 6,090 participants found atypical antipsychotics probably reduce agitation slightly (standardized mean difference −0.21) and probably have a negligible effect on psychosis (−0.11), both at moderate certainty.
  • Switching to an older agent is not a safety move. Conventional antipsychotics carried a higher adjusted risk of death than atypicals at every interval in a 22,890-patient cohort.

When they are indicated

The American Psychiatric Association’s guideline is a narrow indication, not an absent one. Outside imminent-danger situations, use only when symptoms are severe, dangerous, or causing significant distress; review the response to non-pharmacological approaches first; start low and titrate to the minimum effective dose; if no clinically significant response after a four-week trial, taper and withdraw; if there is a response, attempt a taper within four months unless prior attempts caused recurrence; assess at least monthly during the taper and for four months after; and outside delirium, do not use haloperidol first-line.

Chemical restraint is a different thing

A sedative or antipsychotic used to manage behavior rather than to treat a diagnosed condition is a chemical restraint. It is the more common of the two kinds of restraint and the harder to see, because it appears in the chart as a medication rather than as an event. The distinction is not the drug; it is the reason. Restraint-free care.

Other harms, all observational

  • Stroke: rate ratio 1.73 (95% CI 1.60 to 1.87) during exposed periods in a self-controlled case series of 6,790 patients, and 3.50 (95% CI 2.97 to 4.12) in those with dementia.
  • Pneumonia: odds ratio 2.61 for atypicals and 1.76 for conventionals versus past use, dose-dependent; a separate cohort found the risk highest in the first week after starting (odds ratio 4.5).
  • Fracture: in 1,540,915 Danes aged 65 and over, incidence rate ratios in the first 30 days after initiation from 1.97 for risperidone to 2.98 for haloperidol.

What the evidence does and does not show

Sedating medications impair gait, balance and reaction time, and their labels say so. That part is not in doubt. What has not been shown is that a deprescribing program reduces fall rates — the trials that tested it were small, short, and mostly measured a medication count rather than a fracture. Those are two different questions, and absence of evidence from underpowered trials is not evidence that the drugs do not cause falls. What the evidence actually shows about deprescribing and falls.

What a review of this class looks like

  1. What is the target symptom, and was it ever written down? A prescription with no stated target cannot be evaluated, and a surprising number have none.
  2. Was a non-pharmacological approach tried and reviewed? The guideline requires this before non-emergency use.
  3. Is there a reversible cause that was missed? Pain, infection, constipation, urinary retention, a new anticholinergic, dehydration, an environment the person cannot navigate. Assessment.
  4. Did it work? The four-week checkpoint exists precisely because many prescriptions continue indefinitely without anyone establishing that they helped.
  5. Has a taper been attempted? And if one was attempted and failed, is that recorded — because that record is what identifies the person who should stay on it.

The measure, and the trap inside it

CMS has reported the share of long-stay nursing home residents receiving an antipsychotic falling from 23.9% in the fourth quarter of 2011 to 14.2% in the second quarter of 2025. CMS states that clinical indications exist and that it “does not expect that the national prevalence of antipsychotic medication use will decrease to zero.”

The trap: the withdrawal evidence says most residents can come off safely, and that a specific identifiable minority — those who responded well to the drug for psychosis, aggression or agitation, and those with more severe baseline symptoms — are more likely to relapse. A program that pursues a number rather than the individual will find that minority the hard way, and the harm will not appear in the measure.

Common questions

Should every antipsychotic in a facility be stopped?

No. The guideline indication is narrow but real, and the Cochrane withdrawal review identifies exactly who is likely to relapse. The right posture is a monitored attempt for each person with a plan and a way back, not a target applied to a building. The evidence on antipsychotics in dementia.

What is the difference between an antipsychotic and a chemical restraint?

The reason, not the drug. Treating a diagnosed condition is treatment; using the same drug to manage behavior rather than to treat a condition is restraint. That is why the target symptom being written down at the time of prescribing matters so much. Restraint-free care.

Back to the drug-class library.

References

  1. 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):1934–1943. PMID 16234500 · DOI 10.1001/jama.294.15.1934.
  2. Mühlbauer V, Möhler R, Dichter MN, Zuidema SU, Köpke S, Luijendijk HJ. Antipsychotics for agitation and psychosis in people with Alzheimer’s disease and vascular dementia. Cochrane Database of Systematic Reviews. 2021;12(12):CD013304. PMID 34918337 · DOI 10.1002/14651858.CD013304.pub2.
  3. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. The New England Journal of Medicine. 2005;353(22):2335–2341. PMID 16319382 · DOI 10.1056/NEJMoa052827.
  4. Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia. The American Journal of Psychiatry. 2016;173(5):543–546. PMID 27133416 · DOI 10.1176/appi.ajp.2015.173501.
  5. Yohanna D, Cifu AS. Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia. JAMA. 2017;318(11):1057–1058. PMID 28975291 · DOI 10.1001/jama.2017.11112.
  6. Van Leeuwen E, Petrovic M, van Driel ML, et al. Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia. Cochrane Database of Systematic Reviews. 2018;3(3):CD007726. PMID 29605970 · DOI 10.1002/14651858.CD007726.pub3.
  7. Douglas IJ, Smeeth L. Exposure to antipsychotics and risk of stroke: self controlled case series study. BMJ. 2008;337:a1227. PMID 18755769 · DOI 10.1136/bmj.a1227.
  8. Trifirò G, Gambassi G, Sen EF, et al. Association of community-acquired pneumonia with antipsychotic drug use in elderly patients: a nested case-control study. Annals of Internal Medicine. 2010;152(7):418–425. PMID 20368647 · DOI 10.7326/0003-4819-152-7-201004060-00006.
  9. Knol W, van Marum RJ, Jansen PAF, Souverein PC, Schobben AFAM, Egberts ACG. Antipsychotic drug use and risk of pneumonia in elderly people. Journal of the American Geriatrics Society. 2008;56(4):661–666. PMID 18266664 · DOI 10.1111/j.1532-5415.2007.01625.x.
  10. Torstensson M, Leth-Møller K, Andersson C, Torp-Pedersen C, Gislason GH, Holm EA. Danish register-based study on the association between specific antipsychotic drugs and fractures in elderly individuals. Age and Ageing. 2017;46(2):258–264. PMID 27932365 · DOI 10.1093/ageing/afw209.
  11. Centers for Medicare & Medicaid Services. National Partnership to Improve Dementia Care in Nursing Homes: Antipsychotic Medication Use Data Report. cms.gov. 2026. https://www.cms.gov/files/document/data-report-national-partnership-improve-dementia-care-nursing-homes-antipsychotic-medication-use.pdf.
  12. Lee J, Negm A, Peters R, Wong EKC, Holbrook A. Deprescribing fall-risk increasing drugs (FRIDs) for the prevention of falls and fall-related complications: a systematic review and meta-analysis. BMJ Open. 2021;11(2):e035978. PMID 33568364 · DOI 10.1136/bmjopen-2019-035978.

Bibliographic records on this page were retrieved from PubMed. Every reference links to its DOI or PubMed record.

Written and medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP, founder and medical director of DWARAA. Last reviewed . This page is educational. DWARAA does not prescribe, deprescribe, diagnose or treat.