FPIN's Clinical Inquiries

Pharmacologic Management of Agitation in Patients with Dementia


Am Fam Physician. 2021 Jul ;104(1):91-92.

Clinical Question

Which medications are effective at decreasing agitation in patients with dementia?

Evidence-Based Answer

Selective serotonin reuptake inhibitors (SSRIs) and risperidone (Risperdal) are moderately effective at decreasing agitation in all types of dementia. (Strength of Recommendation [SOR]: A, based on meta-analysis.) Olanzapine (Zyprexa) and risperidone reduce dementia-related agitation much longer than placebo. (SOR: B, based on one high-quality randomized controlled trial [RCT].) Dextromethorphan/quinidine (Nuedexta) may be effective at reducing agitation in patients with dementia. (SOR: B, based on one high-quality RCT cited in meta-analysis.)1

Evidence Summary

A 2018 meta-analysis examining medications used to alleviate agitation in all types of dementia included 36 RCTs with a total of 5,585 participants (mean age = 81.8 years ± 4.9 years; 69.1% female).1 The primary outcome was a 50% reduction in baseline agitation at eight weeks. Twenty individual medications and one combination medication were included in the analyses. Risperidone (odds ratio [OR] = 1.96; 95% CI, 1.49 to 2.59; number needed to treat [NNT] = 6) and SSRIs as a class (OR = 1.61; 95% CI, 1.02 to 2.53; NNT = 25) were more effective than placebo, although no individual SSRI reached statistical significance. Dextromethorphan/quinidine was also more effective than placebo (OR = 3.04; 95% CI, 1.63 to 5.66; NNT = 5), but it was evaluated in only one RCT.

A 2011 Cochrane review assessed the safety and effectiveness of antidepressants for agitation in adults who had one of several different types of dementia, analyzing nine RCTs with a total of 692 patients.2 Five trials compared SSRIs (i.e., sertraline [Zoloft], citalopram [Celexa], fluoxetine [Prozac], and fluvoxamine) with placebo over periods of 17 days to 12 weeks. SSRIs were more effective than placebo and no less safe than placebo or antipsychotics. (SOR = A, based on meta-analysis.) Two trials measured changes in Cohen-Mansfield Agitation Inventory scores (assessing

Address correspondence to Katherine Fortenberry, PhD, at Katie.fortenberry@hsc.utah.edu. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


show all references

1. Kongpakwattana K, Sawangjit R, Tawankanjanachot I, et al. Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis. Br J Clin Pharmacol. 2018;84(7):1445–1456....

2. Seitz DP, Adunuri N, Gill SS, et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;(2):CD008191.

3. Viscogliosi G, Chiriac IM, Ettorre E. Efficacy and safety of citalopram compared to atypical antipsychotics on agitation in nursing home residents with Alzheimer dementia. J Am Med Dir Assoc. 2017;18(9):799–802.

4. Schneider LS, Tariot PN, Dagerman KS, et al.; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006;355(15):1525–1538.

5. 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. Am J Psychiatry. 2016;173(5):543–546.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review.

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or email: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN's Clinical Inquiries published in AFP is available at https://www.aafp.org/afp/fpin.



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