In an elderly patient with Alzheimer’s dementia who has persistent dangerous agitation unresponsive to non‑pharmacologic measures, which antipsychotic is the only one FDA‑approved for this indication and what starting dose should be used?

FDA-Approved Antipsychotic for Dementia-Related Agitation

No antipsychotic is FDA-approved for the treatment of agitation or psychosis in dementia patients. All antipsychotics carry a black-box warning for increased mortality (1.6-1.7 times higher than placebo) when used in elderly patients with dementia-related psychosis. 1

Critical Context: Off-Label Use Only

Despite the lack of FDA approval, risperidone has the strongest evidence base for managing severe, dangerous agitation in Alzheimer's dementia when non-pharmacologic interventions have failed. 1, 2

When to Consider Antipsychotic Use

Antipsychotics should only be used when ALL of the following criteria are met:

• Severe agitation with the patient threatening substantial harm to self or others 1
• Non-pharmacological interventions have been systematically attempted and documented as failed or impossible 1, 3
• Reversible medical causes (pain, UTI, pneumonia, constipation, urinary retention, dehydration, metabolic disturbances) have been investigated and treated 1
• Risk-benefit discussion completed with patient (if feasible) and surrogate decision maker, including mortality risk, cardiovascular effects, stroke risk, falls, and extrapyramidal symptoms 1

Recommended Agent and Dosing

Risperidone (First-Line for Severe Agitation with Psychosis)

Starting dose: 0.25 mg once daily at bedtime 1

Target dose: 0.5-1 mg daily (maximum 2 mg/day) 1, 2

• Titration: Increase by 0.25 mg every 5-7 days based on response and tolerability 1
• Extrapyramidal symptoms become significantly more likely at doses >2 mg/day 1, 2
• Evidence: The landmark 1999 Risperidone Study Group trial (N=625) demonstrated that 1 mg/day significantly reduced psychosis and aggression in severe dementia, with extrapyramidal symptom rates comparable to placebo at this dose 2

Alternative Agents (When Risperidone Fails or Is Not Tolerated)

Quetiapine: Start 12.5 mg twice daily, maximum 200 mg twice daily 1, 3

• More sedating, higher risk of orthostatic hypotension 1, 3
• Preferred in Lewy body dementia due to lower extrapyramidal symptom risk 3

Olanzapine: Start 2.5 mg at bedtime, maximum 10 mg/day 1

• Less effective in patients >75 years old 1
• Generally well-tolerated but carries metabolic risks 1

Critical Safety Requirements

Mandatory Monitoring

• Daily in-person examination to evaluate ongoing need and assess for adverse effects 1
• Extrapyramidal symptoms (tremor, rigidity, bradykinesia) 1
• Falls risk assessment at every visit 1
• QTc prolongation via ECG monitoring 1
• Metabolic changes (weight, glucose, lipids) 1

Duration of Treatment

Use the lowest effective dose for the shortest possible duration 1

• Attempt taper within 3-6 months to determine if still needed 1
• Approximately 47% of patients continue antipsychotics after discharge without clear indication—this must be avoided 1
• Reassess need at every visit using quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q) 1

What NOT to Use

Avoid typical antipsychotics (haloperidol, fluphenazine, thiothixene) as first-line therapy due to 50% risk of tardive dyskinesia after 2 years of continuous use in elderly patients 1

Avoid benzodiazepines for routine agitation management (except alcohol/benzodiazepine withdrawal) due to:

• Increased delirium incidence and duration 1
• Paradoxical agitation in ~10% of elderly patients 1
• Risk of tolerance, addiction, cognitive impairment, respiratory depression, and falls 1

Common Pitfalls to Avoid

• Do not start antipsychotics for mild agitation, unfriendliness, poor self-care, repetitive questioning, or wandering—these behaviors are unlikely to respond 1
• Do not continue antipsychotics indefinitely without documented ongoing need 1
• Do not add antipsychotics without first addressing reversible medical causes 1
• Do not use antipsychotics as first-line—SSRIs (citalopram 10-40 mg/day or sertraline 25-200 mg/day) are preferred for chronic agitation without psychotic features 1

Algorithm Summary

1. Investigate and treat reversible medical causes (pain, infection, metabolic issues) 1
2. Implement intensive non-pharmacological interventions for at least 24-48 hours 1
3. Consider SSRIs for chronic agitation without psychosis, reassess after 4 weeks 1
4. Reserve risperidone 0.25 mg at bedtime for severe, dangerous agitation with psychotic features after steps 1-3 have failed 1, 2
5. Titrate cautiously to 0.5-1 mg daily based on response 1, 2
6. Monitor daily and attempt taper within 3-6 months 1