Evidence-Based Reviews

Antipsychotics for patients with dementia: The road less traveled

Current Psychiatry. 2018 October;17(10):26-32,35-37

References

1. Gardner RC, Valcour V, Yaffe K. Dementia in the oldest old: a multi-factorial and growing public health issue. Alzheimers Res Ther. 2013;5(4):27.
2. Tariot PN, Blazina L. The psychopathology of dementia. In: Morris JC, ed. Handbook of dementing illnesses. New York, NY: Marcel Dekker Inc.; 1993:461-475.
3. 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;294:1934-1943.
4. Lenzer J. FDA warns about using antipsychotic drugs for dementia. BMJ. 2005;330(7497):922.
5. Kales HC, Valenstein M, Kim HM, et al. Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications. Am J Psychiatry. 2007;164(10):1568-1576; quiz 1623.
6. Gill SS, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007;146(11):775-786.
7. Okura T, Plassman BL, Steffens DC, et al. Neuropsychiatric symptoms and the risk of institutionalization and death: the aging, demographics, and memory study. J Am Geriatr Soc. 2011;59:473-481.
8. Banerjee S, Murray J, Foley B, et al. Predictors of institutionalisation in people with dementia. J Neurol Neurosurg Psychiatry. 2003;74:1315-1316.
9. Alexopoulos GS, Jeste DV, Chung H, et al. The expert consensus guideline series. Treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary. Postgrad Med. 2005;Spec No:6-22.
10. Burke AD, Hall G, Yaari R, et al. Pocket reference to Alzheimer’s disease management. Philadelphia, PA: Springer Healthcare Communications; 2015:39-46
11. Burke AD, Burke WJ, Tariot PN. Drug treatments for the behavioural and psychiatric symptoms of dementia. In: Ames D, O’Brien JT, Burns A, eds. Dementia, 5th ed. Boca Raton, FL: CRC Press; 2016:231-252.
12. Royal Australian and New Zealand College of Psychiatrists. Antipsychotics in dementia: best practice guide. https://bpac.org.nz/a4d/resources/docs/bpac_A4D_best_practice_guide.pdf. Accessed September 4, 2018.
13. Nyberg L, Backman L. Cognitive aging: a view from brain imaging. In: Dixon RA, Backman L, Nilsson LG, eds. New frontiers in cognitive aging. Oxford: Oxford Univ Press; 2004:135-60.
14. Huybrechts KF, Gerhard T, Crystal S, et al. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ. 2012;344:e977. doi: 10.1136/bmj.e977.
15. Burke AD, Tariot PN. Atypical antipsychotics in the elderly: a review of therapeutic trends and clinical outcomes. Expert Opin Pharmacother. 2009;10(15):2407-2414.
16. De Deyn PP, Rabheru K, Rasmussen A, et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology.1999;53(5):946-955.
17. De Deyn PP, Jeste DV, Auby P, et al. Aripiprazole in dementia of the Alzheimer’s type. Poster presented at: 16th Annual Meeting of American Association for Geriatric Psychiatry; March 1-4, 2003; Honolulu, HI.
18. Lopez OL, Becker JT, Chang YF, et al. The long-term effects of conventional and atypical antipsychotics in patients with probable Alzheimer’s disease. Am J Psychiatry. 2013;170(9):1051-1058.
19. Mintzer J, Weiner M, Greenspan A, et al. Efficacy and safety of a flexible dose of risperidone versus placebo in the treatment of psychosis of Alzheimer’s disease. In: International College of Geriatric Psychopharmacology. Basel, Switzerland; 2004.
20. 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):918-931.
21. Sultzer DL, Davis SM, Tariot PN, et al; CATIE-AD Study Group. Clinical symptom responses to atypical antipsychotic medications in Alzheimer’s disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry. 2008;165(7):844-854.
22. 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):81-93.
23. Bozymski KM, Lowe DK, Pasternak KM, et al. Pimavanserin: a novel antipsychotic for Parkinson’s disease psychosis. Ann Pharmacother. 2017;51(6):479-487.
24. Moretti R, Torre R, Antonello T, et al. Olanzapine as a possible treatment of behavioral symptoms in vascular dementia: risks of cerebrovascular events. J Neurol. 2005;252:1186.
25. Cole SA, Saleem R, Shea WP, et al. Ziprasidone for agitation or psychosis in dementia: four cases. Int J Psychiatry Med. 2005;35(1):91-98.
26. 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.
27. Horwitz GJ, Tariot PN, Mead K, et al. Discontinuation of antipsychotics in nursing home patients with dementia. Am J Geriatr Psychiatry. 1995;3(4):290-299.

Although the use of antipsychotics for patients with dementia may increase the risk of mortality, the absolute increased risk to a given individual, at least with short-term treatment, is likely small. The risk may also vary depending on the choice of SGA. Patients who were treated with quetiapine had a slightly lower risk of death than those who were treated risperidone.⁵ Death rates among patients prescribed aripiprazole, olanzapine, and ziprasidone were similar to the death rates of patients who were treated with risperidone. Compared with patients who were treated with risperidone, patients who were treated with the FGA haloperidol were twice as likely to die during a subsequent 6-month observation period. The largest number of deaths occurred during the first 40 days of treatment.⁵

While this increased risk of mortality is an important factor to discuss with patients and caregivers when deciding whether to initiate antipsychotic treatment, it is also important to put it into perspective. For example, the risk of suddenly dying from a stroke or heart attack for a person with dementia who is not taking an antipsychotic is approximately 2%. When an individual is started on one of these agents, that risk increases to approximately 4%. While the mortality risk is doubled, it remains relatively small.⁴ When faced with verbal or physical assaults, hostility, paranoid ideations, or other psychotic symptoms, many families feel that this relatively low risk does not outweigh the potential benefits of reducing caregiver and patient distress. If nonpharmacologic and/or other pharmacologic interventions have failed, the treatment has reached a point of no good alternatives and therapy should then focus on minimizing risk.

Informed consent is essential. A discussion of risks and benefits with the patient, family, or other decision-makers should focus on the risk of stroke, potential metabolic effects, and mortality, as well as potential worsening of cognitive decline associated with antipsychotic treatment. This should be weighed together with the evidence that suggests psychosis and agitation are associated with earlier nursing home admission and death.^7,8 Families should be given ample time and opportunity to ask questions. Alternatives to immediate initiation of antipsychotics should be thoroughly reviewed.

Despite the above-noted risks, expert consensus suggests that the use of antipsychotics in the treatment of individuals with dementia can be appropriate, particularly in individuals with dangerous agitation or psychosis.⁹ These agents can minimize the risk of violence, reduce patient distress, improve the patient’s quality of life, and reduce caregiver burden. In clinical trials, the benefits of antipsychotics have been modest. Nevertheless, evidence has shown that these agents can reduce psychosis, agitation, aggression, hostility, and suspiciousness, which makes them a valid option when other interventions have proven insufficient.

Target specific symptoms

Despite this article’s focus on the appropriate use of antipsychotics for patients with BPSD, it is important to emphasize that the first-line approach to the management of BPSD in this population should always be a person-centered, psychosocial, multidisciplinary, nonpharmacologic approach that focuses on identifying triggers and treating potentially modifiable contributors to behavioral symptoms. Table 1¹⁰ outlines common underlying causes of BPSD in dementia that should be assessed before prescribing an antipsychotic.

Continued to: Alternative psychopharmacologic treatments...

Antipsychotics for patients with dementia: The road less traveled

References

Target specific symptoms

Pages

Recommended Reading