What is the recommended dosing of Rexulti (brexpiprazole) for a geriatric patient with dementia?

Rexulti (Brexpiprazole) Should Not Be Used for Dementia Treatment

Rexulti (brexpiprazole) is not recommended for routine use in geriatric patients with dementia, and if used specifically for agitation associated with Alzheimer's disease dementia where it is FDA-approved, dosing should be initiated at 0.5 mg daily and titrated slowly to a target range of 2-3 mg/day over several weeks. 1

Critical Safety Context

• All antipsychotics, including brexpiprazole, carry a black box warning for increased mortality risk in elderly patients with dementia-related psychosis. 2
• Antipsychotics should only be considered when patients pose hazards to themselves or others, and should be discontinued after 3 months if used. 2
• Non-pharmacological interventions must be exhausted first, including establishing predictable routines, environmental modifications, and structured exercise programs. 2

Evidence-Based Treatment Algorithm for Dementia

First-Line Approach: Non-Pharmacological Interventions

• Implement the "three R's" approach (repeat, reassure, redirect), structured daily routines, and environmental modifications before any medication. 3, 2
• Address reversible causes: treat pain, check for urinary tract infections, pneumonia, constipation, and review medications for anticholinergic agents that worsen confusion. 4

Second-Line: Cholinesterase Inhibitors

• For cognitive symptoms and mild behavioral disturbances, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are first-line and may improve neuropsychiatric symptoms. 2
• Donepezil should be started at 5 mg daily and increased to 10 mg after 4-6 weeks. 2
• Memantine is recommended for moderate-to-severe disease, alone or combined with cholinesterase inhibitors. 3, 2

Third-Line: SSRIs for Persistent Agitation

• For chronic agitation unresponsive to cholinesterase inhibitors, SSRIs (citalopram or sertraline) are the preferred pharmacological treatment. 4, 2
• Start citalopram at 10 mg/day and assess response at 4 weeks. 4
• SSRIs have minimal anticholinergic side effects compared to other options. 3

Last Resort: Antipsychotics (Including Brexpiprazole)

• Only use when patients pose immediate danger to self or others after all other options have failed. 2
• Antipsychotics should be avoided as first-line treatment due to high risk of mortality, cerebrovascular events, and tardive dyskinesia. 4, 2

Brexpiprazole Dosing Protocol (If Absolutely Necessary)

If brexpiprazole is deemed necessary for agitation associated with Alzheimer's disease dementia:

• Starting dose: 0.5 mg once daily 1
• Titration: Increase slowly by 0.5 mg increments weekly as tolerated 1
• Target dose: 2-3 mg/day 1
• Maximum studied dose: 3 mg/day 1

Monitoring Requirements

• Monitor for treatment-emergent adverse events, particularly headache (most common at 7.6%), extrapyramidal symptoms (5.3%), somnolence/sedation (3.7%), and cerebrovascular events (0.5%). 1
• Assess weight, cardiovascular status, and cognitive function regularly. 1
• Discontinue after 3 months if used, per guideline recommendations. 2

Common Pitfalls to Avoid

• Do not use benzodiazepines for agitation in elderly patients due to increased risk of delirium and paradoxical agitation. 4
• Avoid anticholinergics (diphenhydramine, hydroxyzine, oxybutynin) as they worsen cognitive function in dementia. 2
• Do not prescribe typical antipsychotics as first-line due to high risk of tardive dyskinesia. 4
• Monitor for polypharmacy, as multiple medications increase risk of adverse effects and interactions. 2

Comparative Context with Other Antipsychotics

While risperidone has been studied more extensively in dementia (with effective doses of 0.5-2 mg/day), 5, 6 brexpiprazole represents a newer option with potentially similar efficacy but requires doses of 2-3 mg/day for agitation. 1 However, the fundamental principle remains: all antipsychotics should be avoided unless absolutely necessary due to safety concerns in this vulnerable population. 2