Special Guest Author: Billy Smith, MD
Blanca is a 75 yo woman with a history of mild Alzheimer’s Dementia (AD), hypertension, and hyperlipidemia. She lives at home with her husband, and her daughter lives across the street. She can attend to all her Activities of Daily Living (ADLs), including bathing and dressing. She is no longer able to perform Instrumental Activities of Daily Living (IADLs) independently, such as managing the household and the finances. When she misplaces something, she becomes more irritable and anxious, perseverating on her family stealing her belongings. Behavioral strategies (see prior PsychSnap) were helpful to some extent, but her anxiety persisted. She started taking donepezil, titrated to 10mg daily, which was helpful for several months. Escitalopram, titrated to 10mg daily, was then added with subsequent relief of anxiety and agitation (see Part 1 of this PsychSnap).
Unfortunately, after a year, Blanca became progressively more agitated with paranoid themes related to her husband, despite remaining independent in all of her ADLs. She began to share beliefs that her husband was leaving the house to have affairs with other women and that he was gambling her money away. The family reports that these beliefs were untrue. They struggled to redirect Blanca when she was distressed.
Two weeks ago, Blanca grabbed a knife and threatened to stab her husband if he kept lying to her. The family has removed or limited access to potentially dangerous objects, including knives, by hiding them on a high shelf. They feel quite helpless in managing her paranoia. Your team contacted adult protective services (APS) to complete a report because Blanca’s husband who was threatened is an older adult. The APS report resulted in an increase in in-home support service hours for Blanca. The family asks you if there are other medications to help with Blanca’s paranoia and agitation.
Using antipsychotic medications to manage the neuropsychiatric symptoms of AD
Delusional thought content in Alzheimer’s dementia is common (~31% prevalence) and most frequently seen in the middle stages of the disease. It often resolves as patients progress to late-stage dementia. Themes of spousal infidelity or paranoia about people stealing belongings or money are common. While the preferred approach is to maximize behavioral interventions, antipsychotic medications should be considered when psychosis leads to dangerous behaviors, such as threats of harm (APA 2016, Smith 2024).
There are 5 antipsychotic medications that have at least 1 positive trial in treating agitation or psychosis associated with AD. Among these medications, there is no best antipsychotic medication – the choice is often made with shared decision-making, based on medical co-morbidities and side effect profiles. In general, I start with risperidone, aripiprazole, or olanzapine.
| Medication | Starting Dose Target Dose | Key Considerations | Common Adverse Reactions |
|---|---|---|---|
| Risperidone | 0.25-0.5mg bedtime 1-2mg bedtime | potent D2 blockade can help psychosis at low doses; available as an ODT (orally disintegrating tab) | orthostatic hypotension (requires slow titration); falls; extrapyramidal symptoms |
| Aripiprazole | 2.5mg daily 5-10mg daily | less sedating; low risk of metabolic syndrome; available as an ODT and a liquid; less likely to cause QTc prolongation | akathisia; can worsen impulse control |
| Olanzapine | 2.5-5mg bedtime 5-10mg bedtime | may improve sleep cycle disruption; stimulates appetite – consider in patients with poor PO intake; available as an ODT | metabolic syndrome; sedation; anticholinergic side effects |
| Brexpiprazole | 0.5mg daily 2mg daily | FDA approved for the treatment of agitation associated with Alzheimer’s dementia; no head-to-head studies with other antipsychotics | lower risk of akathisia than aripiprazole; $$$ |
| Quetiapine | 12.5-25mg bedtime 50-200mg bedtime | helps insomnia and anxiety; low D2 blockade – can use in patients with Parkinson’s; higher doses needed to treat psychosis. | sedation; orthostatic hypotension (requires slow titration and consistent ongoing adherence); falls; metabolic syndrome |
Risperidone, olanzapine, and quetiapine are usually sedating and dosed at bedtime. However, if daytime agitation is a significant problem, it can help to split the total daily dose between morning and evening.
When using antipsychotic medications to manage psychosis and/or agitation in AD, only one antipsychotic should be tried at a time. If a medication doesn’t help, it should be stopped within 4 weeks. If it does help, the need for continued treatment with an antipsychotic medication should also be reassessed every 4 months, as psychosis can resolve as AD progresses (APA 2016).
Back to Blanca
You have a risk-benefit conversation with Blanca’s family about using an antipsychotic medication to treat Blanca’s psychosis and agitation. You are trying to decrease her distress and improve her quality of life. You discuss the black box warning for the antipsychotic medications as a class. There is an increased risk of death in patients with dementia who are treated with anti-psychotics compared to those who are not (4.5% in treatment group vs 2.6% in placebo group over 10 weeks). This increased risk of death was largely due to stroke.
Blanca starts taking risperidone 0.25mg at bedtime. The dose is titrated up to 1.5mg at bedtime over 6 weeks with close monitoring for orthostasis, falls, sedation, and QTc prolongation. EKGs are done at baseline, after initiation of risperidone 0.25mg, and 1 week after reaching risperidone 1.5mg. Her QTc remained stable, <450ms. Blanca becomes less perseverative on her delusional thought content and has no further episodes of aggressive behavior. She continues to live at home with her husband with in-home support services.
Guest Author Billy Smith, MD is a geriatric psychiatrist and an assistant professor at UCSF.
Key Points
- When non-pharmacological approaches to managing behavioral disturbances in dementia are insufficient, acetylcholinesterase inhibitors, SSRIs, and second generation antipsychotic medications should be considered.
- Five antipsychotics have positive trials for psychosis or agitation associated with Alzheimer’s dementia (risperidone, aripiprazole, olanzapine, brexpiprazole, quetiapine). Medical co-morbidities and side effect profiles guide the choice of a specific medication.
- If an antipsychotic medication is helpful, re-evaluate the need for it every 4 months, as psychosis may resolve as dementia progresses.
Related PsychSnaps:
“What medications can be used to manage the neuropsychiatric symptoms of Alzheimer’s Disease?” Billy Smith, July 2024
“How do you manage behavioral and psychological symptoms in a patient with dementia?” Anna Chodos, Anna Hines, Ashley Johnson, July 2023
References:
American Psychiatric Association. The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. American Psychiatric Association, 2016. https://doi.org/10.1176/appi.books.9780890426807
Mühlbauer, V., Möhler, R., Dichter, M. N., Zuidema, S. U., Köpke, S., & Luijendijk, H. J. (2021). Antipsychotics for agitation and psychosis in people with Alzheimer’s disease and vascular dementia. Cochrane Database of Systematic Reviews, 2022(1).
Schneider, Lon S., et al. “Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease.” New England Journal of Medicine 355.15 (2006): 1525-1538.
Sink, Kaycee M., Karen F. Holden, and Kristine Yaffe. “Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence.” Jama 293.5 (2005): 596-608.
Smith, William B., et al. “Psychotic Symptoms and Syndromes.” Age-Adjusted Psychiatric Treatment for the Older Patient. Cham: Springer Nature Switzerland, 2024. 173-194.