What is the recommended initial titration dose of Rexulti (brexpiprazole) for a 70-year-old female patient with Alzheimer's disease, agitation, and paranoia?

Brexpiprazole (Rexulti) Dosing for Alzheimer's Disease with Agitation and Paranoia

For a 70-year-old female with Alzheimer's disease and agitation/paranoia, you should titrate brexpiprazole to 1 mg daily and reevaluate before considering an increase to 2 mg due to safety concerns in elderly patients with dementia.

Important Safety Considerations

• BLACK BOX WARNING: Brexpiprazole carries an FDA black box warning regarding increased mortality risk in elderly patients with dementia-related psychosis 1
• Brexpiprazole is not FDA-approved for dementia-related psychosis, though it has recently become the first approved medication specifically for agitation associated with Alzheimer's disease 2, 3
• All antipsychotics can prolong QTc interval, requiring careful monitoring in elderly patients 4

Dosing Algorithm for Brexpiprazole in Elderly Patients with Alzheimer's

1. Initial Dosing:

   • Start at 0.5 mg daily for 4-7 days
   • Titrate to 1 mg daily over 1-2 weeks
   • Monitor for side effects and clinical response

2. Evaluation Period (2-4 weeks at 1 mg):

   • Assess efficacy using validated tools (e.g., Cohen-Mansfield Agitation Inventory)
   • Monitor for adverse effects:
     • Dizziness, headaches, somnolence
     • QTc prolongation
     • Extrapyramidal symptoms
     • Orthostatic hypotension

3. Dose Adjustment Decision:

   • If good response at 1 mg with minimal side effects: maintain dose
   • If inadequate response and good tolerability: consider increasing to 2 mg
   • If poor tolerability: reduce dose or consider alternative treatment

Evidence Supporting 1 mg Before 2 mg Approach

Clinical trials have shown that while 2 mg/day demonstrated statistically significant improvement in agitation symptoms, the 1 mg/day dose should be tried first in elderly patients due to:

• Age-related pharmacokinetic changes affecting drug metabolism 1
• Higher risk of adverse effects in elderly patients 4, 5
• Clinical trial data showing efficacy of brexpiprazole at 2 mg/day for agitation in Alzheimer's disease, but with increased side effects compared to lower doses 5

Special Considerations for This Patient

• Age (70 years): Increased risk for adverse effects; consider starting at lower dose
• Renal function: If CrCl <60 mL/min, maximum recommended dose is 2 mg daily 1
• Hepatic function: If moderate to severe impairment, maximum dose is 2 mg daily 1
• Medication interactions: Check for CYP2D6 inhibitors (e.g., SSRIs) or CYP3A4 inhibitors/inducers that may require dose adjustment 1
• QTc monitoring: Consider baseline ECG and follow-up monitoring, especially if QTc >450 ms 4

Monitoring Plan

• Schedule follow-up within 2 weeks to assess response
• Monitor:
  • Agitation/paranoia symptoms
  • Cognitive function
  • Fall risk
  • Vital signs including orthostatic blood pressure
  • Side effects (sedation, dizziness, extrapyramidal symptoms)
  • Consider ECG if on other QTc-prolonging medications

Common Pitfalls to Avoid

1. Skipping the 1 mg evaluation period and moving directly to 2 mg
2. Failing to monitor for QTc prolongation
3. Not considering drug interactions that may affect brexpiprazole metabolism
4. Using brexpiprazole "as needed" (it's a maintenance medication, not for PRN use) 2
5. Continuing treatment without regular reassessment of benefit vs. risk

Remember that brexpiprazole should only be used after non-pharmacological approaches have been tried, and treatment should be limited to the shortest duration necessary due to the increased mortality risk in elderly patients with dementia.