What is the next step in managing agitation in a dementia patient who has failed zolpidem and trazodone?

Brexpiprazole (Rexulti) for Agitation in Dementia

Brexpiprazole (Rexulti) is the recommended medication for this patient with dementia and agitation who has failed zolpidem, trazodone, and non-pharmacological interventions, as it is the only FDA-approved medication specifically for agitation in Alzheimer's dementia with demonstrated efficacy and a better safety profile than other antipsychotics. 1, 2

Rationale for Brexpiprazole

• First and only FDA-approved medication specifically for agitation in Alzheimer's dementia (approved May 2023) 2
• Demonstrated efficacy in multiple Phase 3 clinical trials with significant improvement in agitation symptoms compared to placebo 3
• Better safety and tolerability profile compared to other antipsychotics used off-label 2, 4

Dosing and Administration

• Starting dose: 0.5-1 mg/day 1
• Target dose: 2-3 mg/day (shown effective in clinical trials) 3
• Titration: Increase slowly over several weeks to minimize side effects
• Administration: Once-daily oral dosing 5

Important Points to Discuss with Family

1. Efficacy Timeline:

   • Takes 6-12 weeks to show full effect 6
   • May need bridging strategies during this period

2. Safety Considerations:

   • Contains FDA black box warning (like all antipsychotics) for increased mortality risk in elderly patients with dementia 1
   • Generally well-tolerated in clinical trials with discontinuation rates due to adverse events similar to placebo (5.3% vs 4.3%) 3
   • No treatment-emergent adverse events occurred at ≥5% incidence and greater than placebo 3

3. Monitoring Requirements:

   • Regular follow-up within 1-2 weeks after medication changes 1
   • Monitor for sedation, orthostatic hypotension, QT prolongation, metabolic side effects
   • Reassess medication need within 3-6 months 1

Advantages Over Previously Failed Treatments

• Versus Trazodone: Specifically studied and approved for dementia-related agitation; trazodone has limited evidence for this indication 7
• Versus Zolpidem: Zolpidem (benzodiazepine-like agent) should be avoided in elderly with dementia due to increased fall risk, cognitive impairment, and dependence 1

Caveats and Limitations

• Small effect size in clinical trials, though particularly beneficial for severe agitation/aggression 6
• All antipsychotics carry mortality risks in elderly patients with dementia
• Should be used for the shortest duration possible with regular reassessment 1
• Continue non-pharmacological approaches alongside medication 7, 1

Alternative Options if Brexpiprazole Fails

If brexpiprazole is ineffective or not tolerated, consider:

1. Atypical antipsychotics (off-label):

   • Risperidone: Starting dose 0.25mg/day, maximum 2mg/day 7
   • Olanzapine: Starting dose 2.5mg/day, maximum 10mg/day 7
   • Quetiapine: Starting dose 12.5mg twice daily 7

2. Mood stabilizers (off-label):

   • Divalproex sodium: Starting dose 125mg twice daily 7

Remember that brexpiprazole represents a significant advance as the first medication specifically approved for agitation in Alzheimer's dementia, with demonstrated efficacy and tolerability in this vulnerable population.