What is the role of Rexulti (brexpiprazole) in managing Behavioral and Psychological Symptoms of Dementia (BPSD)?

Brexpiprazole for Behavioral and Psychological Symptoms of Dementia (BPSD)

Brexpiprazole is not approved for the treatment of patients with dementia-related psychosis and should not be used for BPSD due to increased mortality risk in elderly patients with dementia. 1

Safety Concerns and FDA Warning

Brexpiprazole carries a black box warning specifically stating that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. The FDA label explicitly states that brexpiprazole is not approved for the treatment of patients with dementia-related psychosis 1.

First-Line Management for BPSD

Non-pharmacological interventions should always be considered as first-line management for behavioral and psychological symptoms of dementia:

• Person-centered care approaches should be implemented before considering any pharmacological interventions 2
• Structured and tailored activities that are individualized to the patient's capabilities and interests 2
• Environmental adaptations to reduce triggers for agitation 3
• Caregiver training to better manage behavioral symptoms 3

Assessment Before Considering Any Medication

Before considering any medication for BPSD:

• Assess for type, frequency, severity, pattern, and timing of symptoms 2
• Evaluate for pain and other potentially modifiable contributors to symptoms 2
• Use the ABC (antecedent-behavior-consequences) charting approach to identify triggers 2
• Rule out delirium, infections, and metabolic causes 2

Pharmacological Options When Non-Pharmacological Approaches Fail

If pharmacological treatment becomes necessary (only when symptoms are severe, dangerous, or cause significant distress):

1. SSRIs (such as citalopram) should be considered as first-line pharmacological treatment for agitation before antipsychotics 2, 3

2. Antipsychotics should only be used when:

   • Symptoms are severe, dangerous, or causing significant distress 2
   • Non-pharmacological interventions have failed 2
   • Benefits outweigh the known mortality risks 2
   • Used at the lowest effective dose for the shortest duration 2

3. If an antipsychotic is deemed necessary:

   • Treatment should be initiated at a low dose and titrated to the minimum effective dose 2
   • If no clinically significant response after 4 weeks, the medication should be tapered and withdrawn 2
   • Regular reassessment is required to determine if continued treatment is necessary 2

Important Considerations

• All antipsychotics (including brexpiprazole) increase mortality risk in elderly patients with dementia 1
• The WHO guidelines specifically advise against using antipsychotics as first-line management for BPSD 2
• Despite recent research suggesting brexpiprazole may have efficacy for agitation in Alzheimer's disease 4, 5, the FDA black box warning and mortality risk outweigh potential benefits

Alternative Approaches

For patients with moderate to severe agitation requiring pharmacological intervention:

• Consider SSRIs which have shown benefit for agitation and overall neuropsychiatric symptoms 2
• For psychosis specifically, if treatment is absolutely necessary, risperidone has been prioritized in consensus guidelines, but still carries mortality risk 3
• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine are approved for cognitive symptoms in dementia but have limited effect on behavioral symptoms 2

Monitoring

If any antipsychotic is used despite the risks:

• Assess response using quantitative measures 2
• Monitor closely for adverse effects including sedation, falls, extrapyramidal symptoms, and cerebrovascular events 4
• Discontinue if clinically significant side effects occur 2

Remember that the evidence consistently shows non-pharmacological approaches should be exhausted before considering any medication for BPSD, and brexpiprazole specifically is contraindicated for dementia-related psychosis due to mortality risk.