From the Guidelines
Neither olanzapine nor quetiapine is clearly safer for treating aggression in patients with dementia, as both carry significant risks, including increased mortality, as highlighted by the American Psychiatric Association practice guideline 1. When considering the treatment of aggression in patients with dementia, it is essential to weigh the potential benefits against the harms of antipsychotic medications. The American Psychiatric Association practice guideline 1 emphasizes the importance of judicious use of these medications, given their association with clinically significant adverse effects, including mortality.
Key Considerations
- Both olanzapine and quetiapine are antipsychotics with FDA black box warnings for increased mortality in elderly patients with dementia-related psychosis.
- Quetiapine may have a slightly lower risk of extrapyramidal symptoms (movement disorders) and might be preferred in patients with Parkinson's disease.
- Olanzapine tends to cause more metabolic issues like weight gain and diabetes.
- Non-pharmacological approaches should always be tried first, including identifying and addressing underlying causes of aggression, modifying the environment, and using behavioral interventions.
Treatment Approach
- When treatment is necessary, these medications should be used at the lowest effective dose for the shortest duration possible.
- Typically, starting quetiapine at 12.5-25mg or olanzapine at 2.5mg daily, with careful monitoring, is recommended.
- Any antipsychotic use in dementia patients should involve careful discussion of risks and benefits with patients and caregivers, with regular reassessment to determine if continued treatment is necessary, as suggested by the guideline 1.
From the FDA Drug Label
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. ZYPREXA is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning, Use in Specific Populations (8. 5), and Patient Counseling Information (17)]. In placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than placebo-treated patients (3.5% vs 1.5%, respectively). Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly patients with dementia-related psychosis.
The FDA drug label does not provide a direct comparison between olanzapine and quetiapine for treating aggression in patients with dementia. However, based on the available information, olanzapine is not approved for the treatment of patients with dementia-related psychosis and has been associated with an increased risk of death and cerebrovascular adverse events in elderly patients with dementia-related psychosis 2.
- Key risks associated with olanzapine in elderly patients with dementia-related psychosis include:
- Increased risk of death
- Cerebrovascular adverse events (e.g., stroke, transient ischemic attack)
- No conclusion can be drawn regarding the safety of quetiapine compared to olanzapine for this specific indication, as the provided drug labels do not contain relevant information.
From the Research
Comparison of Olanzapine and Quetiapine
- Olanzapine and quetiapine are both atypical antipsychotics used to treat aggression in patients with dementia 3, 4.
- A study found that olanzapine was effective in reducing aggression in patients with Alzheimer's disease, but was associated with a higher incidence of serious adverse cerebrovascular events and extra-pyramidal side effects 3.
- Quetiapine has also been shown to be effective in treating agitation and aggression in patients with dementia, with a relatively good tolerability profile 4, 5, 6.
- A randomized, double-blind, placebo-controlled study found that quetiapine 200mg/day was effective and well-tolerated for treating agitation associated with dementia, with no significant difference in cerebrovascular adverse events compared to placebo 5.
Safety Concerns
- Both olanzapine and quetiapine have been associated with an increased risk of mortality in elderly patients with dementia, although the evidence is not consistent across all studies 3, 5.
- Olanzapine has been linked to a higher incidence of serious adverse cerebrovascular events and extra-pyramidal side effects compared to quetiapine 3.
- Quetiapine has been associated with a higher incidence of somnolence and orthostatic hypotension, particularly at higher doses 5, 6.
Efficacy
- Olanzapine has been shown to be effective in reducing aggression and psychosis in patients with Alzheimer's disease, although the evidence is based on a limited number of studies 3, 4.
- Quetiapine has been found to be effective in treating agitation and aggression in patients with dementia, with some studies suggesting a positive response in patients with dementia with Lewy bodies 5, 6.