In an 80‑year‑old woman taking alprazolam 0.25 mg daily at noon, valproic acid (Depakote) 250 mg twice daily, risperidone 0.5 mg twice daily, levetiracetam (Keppra), losartan, and nifedipine, who remains combative and agitated with staff throughout the day, what medication adjustments are recommended to control her agitation?

Medication Management for Persistent Agitation and Combativeness in an 80-Year-Old Woman

Immediate Action: Discontinue Alprazolam

Your first priority is to taper and discontinue alprazolam, as benzodiazepines worsen agitation in approximately 10% of elderly patients through paradoxical reactions and should not be used for routine agitation management in dementia. 1, 2

• Alprazolam is likely worsening her combativeness rather than helping, as paradoxical agitation is well-documented in elderly patients taking benzodiazepines 1, 2
• The FDA label specifies that elderly patients are "especially sensitive to the effects of benzodiazepines" and require gradual dose reduction of no more than 0.25 mg every 3 days 3
• For this patient on 0.25 mg daily, taper by 0.125 mg (half tablet) every 3–4 days over approximately 1–2 weeks while monitoring for withdrawal symptoms 3

Critical Medical Workup Before Any Medication Changes

Before adjusting psychotropics, systematically investigate and treat reversible causes that commonly drive combativeness in elderly patients who cannot verbally communicate discomfort. 1

Essential investigations:

• Pain assessment using observational scales (facial grimacing, guarding, resistance to movement), as untreated pain is a major contributor to aggression 1
• Urinary tract infection and pneumonia screening with urinalysis and chest examination 1
• Constipation and urinary retention evaluation, both of which significantly worsen agitation 1
• Metabolic panel to identify dehydration, electrolyte abnormalities, or hypoxia 1
• Medication review to identify anticholinergic agents (if any) that worsen confusion 1

Optimize Current Antipsychotic Regimen

Your current risperidone dose of 0.5 mg twice daily (1 mg total) is appropriate and within the recommended range, but timing may need adjustment if agitation follows a pattern. 4

If agitation is worse in the morning:

• Redistribute risperidone to provide higher morning coverage: 0.5 mg at 6 AM, 0.25 mg at noon, 0.25 mg at 5 PM (maintaining 1 mg total daily) 1
• The FDA label supports flexible dosing schedules within the 1–6 mg daily range for behavioral symptoms 4

If agitation is constant throughout the day:

• Consider increasing risperidone gradually to 0.5 mg three times daily (1.5 mg total), as the effective dose range extends to 6 mg daily 4
• Titrate in 0.25–0.5 mg increments at intervals of at least one week, monitoring for extrapyramidal symptoms (which increase above 2 mg daily) 1, 4

Add SSRI as First-Line for Chronic Agitation

If behavioral interventions and medical workup fail to control agitation after 2–4 weeks, add an SSRI as the preferred pharmacological option for chronic agitation in dementia. 1

Recommended SSRI regimen:

• Sertraline 25 mg once daily in the morning, increasing by 25 mg weekly to a target of 100–200 mg daily 1
• Alternative: Citalopram 10 mg once daily, increasing by 10 mg weekly to a maximum of 40 mg daily (FDA maximum for elderly due to QTc concerns) 1
• SSRIs require 4 weeks at adequate dosing before assessing response; use quantitative measures like the Cohen-Mansfield Agitation Inventory to track improvement 1
• If no clinically meaningful benefit after 4 weeks at target dose, taper and discontinue 1

Valproate (Depakote) Considerations

Your current Depakote dose of 250 mg twice daily is reasonable for mood stabilization, but verify therapeutic levels and monitor for adverse effects. 1

• Check valproic acid trough level (target 50–100 mcg/mL for behavioral symptoms) and adjust dose accordingly 1
• Monitor liver enzymes and platelet count, as valproate can cause hepatotoxicity and thrombocytopenia in elderly patients 1
• Depakote is appropriate for severe agitation without psychotic features when antipsychotics are contraindicated or ineffective 1

Critical Safety Warnings

All antipsychotics increase mortality risk 1.6–1.7 times higher than placebo in elderly dementia patients; this must be discussed with the patient's surrogate decision maker. 1

• Additional risks include cerebrovascular events, falls, QT prolongation, metabolic changes, and extrapyramidal symptoms 1
• Use the lowest effective dose for the shortest duration, with daily in-person evaluation to assess ongoing need 1
• Attempt taper within 3–6 months to determine if still needed, as approximately 47% of patients continue antipsychotics without clear indication 1

What NOT to Do

• Do not add benzodiazepines (including lorazepam or clonazepam) for agitation management, as they worsen delirium and cause paradoxical agitation in 10% of elderly patients 1
• Do not use typical antipsychotics (haloperidol, fluphenazine) as first-line due to 50% risk of tardive dyskinesia after 2 years in elderly patients 1
• Do not add multiple psychotropics simultaneously without first addressing reversible medical causes and optimizing existing medications 1

Non-Pharmacological Interventions (Mandatory First-Line)

Environmental modifications and behavioral strategies must be attempted and documented as failed before adding medications. 1

• Use calm tones, simple one-step commands, and gentle touch rather than complex instructions 1
• Ensure adequate lighting and reduce excessive noise to minimize overstimulation 1
• Establish predictable daily routines with structured activities during peak agitation times 1
• Provide at least 30 minutes of sunlight exposure daily to help regulate circadian rhythms 1
• Use ABC charting (antecedent-behavior-consequence) to identify specific triggers of combative behavior 1

Monitoring Protocol

• Daily assessment of agitation severity using quantitative scales 1
• Weekly monitoring for extrapyramidal symptoms (tremor, rigidity, bradykinesia) 1
• Monthly reassessment of ongoing medication need with consideration of dose reduction 1
• ECG monitoring if QTc-prolonging medications are combined (risperidone + citalopram) 1