Zyprexa (Olanzapine) Use in Elderly Patients with Dementia
Zyprexa (olanzapine) should NOT be used in elderly patients with dementia-related psychosis due to increased mortality risk and significantly elevated cerebrovascular adverse events including stroke. 1, 2
FDA Black Box Warning and Regulatory Position
The FDA explicitly states that olanzapine is not approved for elderly patients with dementia-related psychosis due to increased death risk in this population. 1
Elderly patients with dementia-related psychosis treated with olanzapine had a significantly higher incidence of cerebrovascular adverse events (stroke, transient ischemic attack) compared with placebo. 1
Mortality incidence was significantly higher in olanzapine-treated patients (3.5%) compared to placebo (1.5%), representing more than double the risk. 3
The incidence of cerebrovascular events was approximately 3 times higher in olanzapine-treated patients (1.3%) versus placebo (0.4%). 3
When Antipsychotics Might Be Considered (Despite Risks)
If prescribers elect to use antipsychotics despite these warnings, they should be regarded only as rescue medications for specific situations: 2
- Acute-onset behavioral symptoms (developing over hours or days, not chronic symptoms developing over weeks to months) 2
- Severe chronic behavioral and psychological symptoms of dementia (BPSD) that have failed other interventions 2
- Patients who are aggressive and/or represent a danger to themselves or others 2
Dosing Guidelines If Use Is Deemed Necessary
If olanzapine must be used despite contraindications, the American Academy of Family Physicians recommends: 4
- Initial dose: 2.5-5 mg at bedtime 4
- Maximum dose: 10 mg daily in divided doses 4
- Doses used in dementia trials ranged from 2.5-7.5 mg/day 5
Mandatory Risk Factor Screening and Monitoring
Before initiating olanzapine in elderly dementia patients, physicians must: 2, 3
- Screen for cerebrovascular disease history (absolute contraindication if present) 2
- Screen for cardiovascular disease risk factors 2
- Identify specific mortality risk factors: age ≥80 years, concurrent benzodiazepine use, pulmonary conditions 3
- Monitor regularly for: excessive sedation, cognitive impairment, fall risk, extrapyramidal symptoms, orthostatic hypotension 4, 1
- Assess for delirium development, particularly in patients with severe dementia, as olanzapine's anticholinergic effects can precipitate delirium 6
Preferred Alternative Approaches
Cholinesterase inhibitors (particularly rivastigmine) are more appropriate for chronic mild-to-moderate BPSD as they can delay onset and reduce severity of neuropsychiatric symptoms while decreasing the requirement for antipsychotics. 2
For behavioral control when antipsychotics are avoided: 7
- Mood stabilizers (divalproex sodium, carbamazepine, trazodone) for severe agitated, repetitive, and combative behaviors 7
- Trazodone 25 mg/day initially (maximum 200-400 mg/day in divided doses) for agitation 7
- Divalproex sodium 125 mg twice daily (titrate to therapeutic level 40-90 mcg/mL), generally better tolerated than other mood stabilizers 7
Critical Safety Considerations
Typical antipsychotics should be avoided entirely as they carry a 50% risk of irreversible tardive dyskinesia after 2 years of continuous use in elderly patients, along with severe cholinergic, cardiovascular, and extrapyramidal side effects. 7
Never combine two antipsychotics (e.g., olanzapine with haloperidol) due to increased adverse effects without additional benefit. 4
Deprescribing guidelines recommend tapering and discontinuation of antipsychotics in dementia patients when behavioral symptoms are controlled or when risks outweigh benefits. 7