Appropriate Use of Antipsychotics in Dementia

Contributed by: Dr. Karenn Chan MD, CCFP, CAC COE - View bio

Case

Cecilia Moore is a 65-year-old woman diagnosed four years ago with early onset Alzheimer’s disease. Cecilia moved to designated supportive living four months ago because her husband could no longer manage her symptoms at home. Her husband reported that, while home Cecilia was not sleeping at night, she would wander around the house mumbling to herself and would see things that were not there. Her family doctor prescribed her trazodone, with escalating doses up to 100 mg and mirtazapine 15 mg to try to treat both her anxiety and insomnia, but both were without significant effect. At the facility where she lives, Cecilia remains on these medications but continues to react to visual hallucinations and has reported that people are killing babies there. She is fearful of the caregivers and will fight, bite and kick when they try to help her with her personal care, which has resulted in some staff injuries.

Issue

When is it appropriate to use antipsychotics for the behavioral and psychological symptoms of dementia?

Background

Behavioral and psychological symptoms of dementia (BPSD) commonly occur sometime during the course of the illness. These symptoms range from apathy, wandering and sleep disturbances to florid symptoms of psychosis. Although symptoms of dementia-related psychosis are not the most prominent BPSD symptoms, studies with population sampling have shown that the prevalence of delusions ranges from 18-25%, hallucinations in 10-15% and agitation or aggression in 9-30%.^{1, 2, 3}

In Canada, atypical antipsychotic medications are primarily indicated for schizophrenia and bipolar disorder, and as an adjunctive treatment for major depressive disorder. The atypical antipsychotic risperidone is the only antipsychotic indicated for short-term use to treat aggression or psychotic symptoms in severe Alzheimer’s type dementia. In 2015, the indication changed to exclude vascular and mixed type dementias due to safety concerns for use in those populations.⁴ Use of any other antipsychotic is an off-label use of the product.

In the recent past, prescription rates of antipsychotics for patients with dementia living in Canadian nursing homes were as high as 26-27%.⁵ There is evidence that antipsychotics are more frequently used in nursing home residents compared to people living with dementia in the community and, within the first month of moving to a nursing home, people were more likely to be started on these medications.⁶ In more recent years, there have been widespread initiatives working to reduce the inappropriate use of antipsychotics and develop evidence-based guidelines on managing antipsychotic use in dementia.^{7, 8}

Evidence

A recent systematic review concluded that antipsychotics (risperidone, olanzapine and aripiprazole) could be used to treat psychosis, aggression and agitation in dementia with modest efficacy, but because of the side effect profile, these medications should be reserved for those with severe symptoms who failed non-pharmacological management.⁹ Quetiapine was found to have limited efficacy.⁹ Patients with dementia with less severe symptoms had less benefit from the medications. The evidence suggests that even when found useful, the efficacy of these medications lasts only 6-12 weeks¹⁰ and consequently should be re-evaluated after that timeframe.

The most serious adverse events associated with use of antipsychotics in people living dementia are adverse cardiovascular events and death. Older adults with dementia who received haloperidol had a 3.8% increase in the risk of death with an NNH of 26; with risperidone increased risk of death was 3.7% with an NNH of 27; olanzapine showed a 2.5% increase (NNH 40); and there was a 2.0% increase (NNH 50) with quetiapine.¹¹ Other common adverse effects include sedation, abnormal gait and extrapyramidal symptoms. The evidence base supports the use of atypical antipsychotics over typical antipsychotics, like haloperidol, due to the more undesirable side effect profile of the first generation of these drugs.

Summary of Important Evidence-Based Guidelines

• Antipsychotics should not be the first choice for treating BPSD.⁸
• Antipsychotics should not be used for primary insomnia.⁸
• Antipsychotics should be used to treat patients with dementia only when agitation and psychosis symptoms are severe, dangerous and/or cause significant distress to the patient.⁷
• Before starting a trial of antipsychotic, potential risks and benefits should be assessed and discussed with the patient/substitute decision maker.⁷
• Treatment should start at the lowest dose and titrated up to the minimum effective dose for that patient, i.e., 0.125 mg risperidone once daily, 2.5 mg olanzapine once daily.⁷
• If there are significant side effects from treatment, risks and benefits should be reviewed again to determine if it should be continued.⁷
• If there is no benefit from the medication after four weeks, taper and withdraw the antipsychotic.⁷
• Plan to review the antipsychotic on a regular basis. In patients who had an adequate response to medication, attempt to taper and withdraw within four months to see if the medication is still needed.⁷

Back to the Case

Cecilia was weaned off the trazodone as it was ineffective. Due to the severity of Cecilia’s symptoms and extreme distress, a trial of antipsychotic was offered to her family after a clear discussion about the potential risks including increased risk of death. Her family was willing to accept this risk as they felt Cecilia had a very poor quality of life and was living in fear. Her family wanted to try anything that might bring her comfort. She was started on a small initial dose of risperidone 0.125 mg p.o. at bedtime, and symptoms and potential side effects were monitored. Reassessment was done every three-to-four weeks with the caregivers reporting decreased hallucinations and distress. Her dose was eventually titrated up to 0.25 mg twice daily, which eliminated her disturbing symptoms of psychosis and allowed her to sleep for longer periods of time in the night. She did continue to have episodes of aggression around her personal care, but ongoing behavioral interventions were able to eliminate this behavior by engaging her to participate in the care of a baby doll before and during her care episodes. After stabilization, her antipsychotic was reviewed every three months and discussions were had with the family about a trial of a slow taper to test if the medication was still needed.

References

1. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of Neuropsychiatric Symptoms in Dementia and Mild Cognitive Impairment: Results From the Cardiovascular Health Study. JAMA. 2002 Sep 25; 288(12):1475-83.
2. Savva GM, Zaccai J, Matthews FE, Davidson JE, McKeith I, Brayne C. Medical Research Council Cognitive Function and Ageing Study: Prevalence, Correlates and Course of Behavioural and Psychological Symptoms of Dementia in the Population. Br J Psychiatry. 2009 Mar;194(3):212-9.
3. Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioural disturbances in dementia: findings from the Cache County Study on Memory and Aging. Am J Psychiatry. 2000 May;157(5):708-14.
4. Government of Canada Recalls and safety alerts. Risperidone-Restriction of dementia indication. [updated Mar 14, 2017, cited Jun 04, 2020] Available from: https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/43797a-eng.php   Accessed June 4, 2020
5. Feng Z , Hirdes JP, Smith TF, Finne-Soveri H, Chi I, Du Pasquier JN, et al. Use of Physical Restraints and Antipsychotic Medications in Nursing Homes: A Cross-National Study. Int J Geriatr Psychiatry. 2009 Oct;24(10):1110-8.
6. Maguire A , Hughes C, Cardwell C, O'Reilly D. Psychotropic Medications and the Transition Into Care: A National Data Linkage Study. J Am Geriatr Soc. 2013 Feb;61(2):215-21.
7. Victor I. Reus VI,  Fochtmann LJ, Eyler AE, Hilty DM, Horvitz-Lennon M, Jibson MD, et al. American Psychiatric Association Practice Guideline On the Use of Antipsychotics To Treat Agitation Or Psychosis In Patients With Dementia. Published online 2016 May 1. Available from: https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2015.173501
8. Choosing Wisely Canada When Psychosis isn’t the Diagnosis: A toolkit for reducing Inappropriate Use of Antipsychotics in Long Term Care. Version 1.2. 2019. [cited Jun 04, 2020] Available from: https://choosingwiselycanada.org/wp-content/uploads/2017/07/CWC_Antipsychotics_Toolkit_v1.0_2017-07-12.pdf
9. Tampi RR, Tampi DJ, Balachandran S, Srinivasan S. Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses. Ther Adv Chronic Dis. 2016 Jul 15; 7(5):229-245.
10.  Ballard CG, Gauthier S,  Cummings JL, Brodaty H, Grossberg GT, Robert P, Lyketsos CG. Management of Agitation and Aggression Associated With Alzheimer Disease. Nat Rev Neurol. May;5(5):245-55.
11. Maust DT, Kim HM, Seyfried LS et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia. JAMA Psychiatry 2015 [cited Jun 4, 2020]. Available from: http://archpsyc.jamanetwork.com/article.aspx?articleid=2203833