For an elderly patient with dementia and agitation, should I start citalopram or brexpiprazole (Rexulti)?

Start with Citalopram First, Not Brexpiprazole (Rexulti)

For an elderly patient with dementia and agitation, you should NOT start with either medication as first-line therapy—begin with nonpharmacological interventions first, and only consider pharmacotherapy if symptoms are severe, dangerous, or cause significant distress. If pharmacotherapy becomes necessary, citalopram is the more appropriate initial choice over brexpiprazole for most patients, as brexpiprazole is specifically indicated only for agitation in Alzheimer's dementia (not other dementias) and carries a black box warning for increased mortality in elderly patients with dementia-related psychosis 1.

Clinical Decision Algorithm

Step 1: Assess Severity and Implement Nonpharmacological Interventions First

The APA guidelines are unequivocal: antipsychotic medications (including brexpiprazole) should only be used when agitation is severe, dangerous, or causes significant patient distress 2. Before considering any medication:

• Assess for reversible causes: pain, infection, constipation, medication side effects, environmental triggers 2
• Document the type, frequency, severity, pattern, and timing of agitation symptoms 2
• Implement and review response to nonpharmacological interventions (behavioral strategies, environmental modifications, caregiver education) 2

Step 2: If Pharmacotherapy Is Necessary

When symptoms meet criteria for pharmacological intervention:

Choose Citalopram if:

• The dementia subtype is uncertain or non-Alzheimer's
• Agitation is mild-to-moderate severity
• Depression is a co-occurring feature
• You want to avoid antipsychotic-related risks (extrapyramidal symptoms, increased mortality)

Consider Brexpiprazole only if:

• Confirmed Alzheimer's disease dementia (brexpiprazole is FDA-approved specifically for agitation in AD dementia, not other dementias) 1
• Agitation is severe and persistent despite nonpharmacological interventions
• Patient/family have been counseled about the black box warning for increased mortality in elderly patients with dementia-related psychosis 1
• You can commit to 6-12 weeks of treatment, as brexpiprazole takes this long to separate from placebo 3, 4

Critical Caveats About Brexpiprazole

Black Box Warning

Brexpiprazole carries an FDA black box warning for increased risk of death in elderly patients with dementia-related psychosis 1. This is not a theoretical concern—it applies to all antipsychotics in this population. The APA guidelines emphasize that antipsychotic benefits are "at best small" while adverse effects including mortality are "clinically significant" 2.

Delayed Onset of Action

Brexpiprazole requires 6-12 weeks to demonstrate efficacy 3, 4. This creates a clinical dilemma: what do you do during this prolonged titration period if agitation remains severe? The medication is not approved for "as needed" use 1.

Limited Indication

Brexpiprazole is only approved for agitation in Alzheimer's disease dementia—not vascular dementia, Lewy body dementia, frontotemporal dementia, or mixed dementias 1. If the dementia subtype is uncertain, brexpiprazole is not appropriate.

Dosing Considerations

If you do use brexpiprazole, start at low doses (2-3 mg/day) as studied in clinical trials 4, 5. The effect size is modest (Cohen's d = 0.30-0.35) 4, 5, meaning the clinical benefit may be subtle.

Why Citalopram Is Often More Practical

While the provided evidence doesn't include citalopram studies, the APA guidelines explicitly state they focus only on antipsychotics and "do not review evidence for or focus on other pharmacological interventions" 2. This is important context: the absence of citalopram in these guidelines doesn't mean it's ineffective—it simply wasn't the focus of this particular guideline.

In clinical practice, SSRIs like citalopram are commonly used for agitation in dementia because they:

• Have a more favorable safety profile than antipsychotics
• Address co-occurring depression and anxiety
• Don't carry the same mortality risk as antipsychotics
• Work across all dementia subtypes

Monitoring and Reassessment

If you start any medication for agitation:

• Use a quantitative measure (like Cohen-Mansfield Agitation Inventory) to track response 2
• If no response after 4 weeks at adequate dose, taper and discontinue 2
• Regularly reassess for side effects and consider tapering if significant adverse effects occur 2
• Discuss ongoing risks/benefits with patient and family, particularly for antipsychotics 2

Bottom Line

Start with nonpharmacological interventions. If medication becomes necessary, citalopram is the safer initial choice for most elderly patients with dementia and agitation. Reserve brexpiprazole for confirmed Alzheimer's disease with severe, persistent agitation after other approaches have failed, and only after thorough discussion of the mortality risk with the patient's family 2, 1.