What alternative medication to brexpiprazole (Rexulti) can be used for agitation in a patient with early-stage dementia when Rexulti is too expensive?

Alternative Medications for Agitation in Early Dementia When Rexulti Is Too Expensive

Start with an SSRI—specifically citalopram 10 mg daily or sertraline 25–50 mg daily—as your first-line pharmacological alternative to brexpiprazole for agitation in early-stage dementia. 1

Why SSRIs Are the Preferred Alternative

SSRIs are explicitly designated as first-line pharmacological treatment for chronic agitation in dementia by multiple guideline bodies, including the American Psychiatric Association and the Canadian Stroke Best Practice Recommendations. 1 These agents significantly reduce overall neuropsychiatric symptoms, agitation, and depression in dementia patients, with a substantially better safety profile than antipsychotics. 1

Citalopram should be started at 10 mg daily (maximum 40 mg daily), while sertraline begins at 25–50 mg daily (maximum 200 mg daily). 1 Both are well-tolerated, though some patients experience nausea or sleep disturbances with citalopram. 1 Sertraline has minimal drug interactions and is particularly suitable if the patient takes multiple medications. 1

Critical Prerequisites Before Any Medication

Before prescribing any psychotropic agent, you must systematically investigate and treat reversible medical causes that commonly drive agitation in early dementia:

• Pain assessment and management—untreated pain is a major contributor to behavioral disturbances in patients who cannot verbally communicate discomfort. 1
• Infections—check for urinary tract infections and pneumonia, which disproportionately trigger neuropsychiatric symptoms. 1
• Metabolic disturbances—evaluate for dehydration, electrolyte abnormalities, hypoxia, and hyperglycemia. 1
• Constipation and urinary retention—both significantly contribute to restlessness and agitation. 1
• Medication review—identify and discontinue anticholinergic agents (diphenhydramine, oxybutynin, cyclobenzaprine) that worsen confusion and agitation. 1

Non-Pharmacological Interventions Must Come First

The American Geriatrics Society and American Psychiatric Association require documented implementation of behavioral interventions before any medication is considered. 1 These include:

• Environmental modifications—adequate lighting (especially late afternoon), reduced noise, predictable daily routines, simplified surroundings with clear labeling. 1
• Communication strategies—calm tones, simple one-step commands, gentle touch, allowing adequate processing time. 1
• Circadian regulation—2 hours of morning bright light at 3,000–5,000 lux, at least 30 minutes of daily sunlight exposure, increased daytime physical and social activities. 1
• Caregiver education—teaching that behaviors are dementia symptoms rather than intentional actions, using the "three R's" approach (repeat, reassure, redirect). 1

SSRI Treatment Protocol

Initiation: Start citalopram 10 mg daily or sertraline 25–50 mg daily. 1 Titrate slowly using increments of the initial dose every 5–7 days until therapeutic benefits appear. 1

Assessment window: Evaluate response after 4 weeks of adequate dosing using quantitative measures such as the Cohen-Mansfield Agitation Inventory or Neuropsychiatric Inventory Questionnaire (NPI-Q). 1

If no response: Taper and withdraw the medication if there is no clinically significant improvement after 4 weeks at adequate dose. 1

If response is achieved: Continue treatment but periodically reassess the need for ongoing medication. 1 Even with positive response, attempt taper after 9 months to determine if still needed. 1

Second-Line Options If SSRIs Fail

If SSRIs are ineffective or not tolerated after an adequate trial, consider:

Trazodone: Start 25 mg daily, maximum 200–400 mg daily in divided doses. 1 Use caution in patients with premature ventricular contractions due to orthostatic hypotension risk. 1 Trazodone is safer than antipsychotics with better tolerability. 1

Divalproex sodium: For severe agitation without psychotic features, start 125 mg twice daily, titrating to therapeutic blood level. 1 Monitor liver enzymes and coagulation parameters. 1

When to Consider Antipsychotics (Last Resort Only)

Reserve antipsychotics exclusively for severe agitation with psychotic features when the patient is threatening substantial harm to self or others AND behavioral interventions plus SSRIs have failed. 1

Risperidone is the preferred antipsychotic if one becomes necessary: start 0.25 mg at bedtime, target dose 0.5–1.25 mg daily, maximum 2–3 mg daily. 1 Extrapyramidal symptoms occur at doses above 2 mg daily. 1

Quetiapine is an alternative: start 12.5 mg twice daily, maximum 200 mg twice daily. 1 More sedating with higher risk of orthostatic hypotension. 1

Critical safety discussion required: Before initiating any antipsychotic, discuss with the patient (if feasible) and surrogate decision maker the 1.6–1.7 times increased mortality risk compared to placebo, cardiovascular effects including QT prolongation and sudden death, cerebrovascular adverse events, falls risk, and metabolic changes. 1

What NOT to Use

Avoid benzodiazepines for routine agitation management—they increase delirium incidence and duration, cause paradoxical agitation in approximately 10% of elderly patients, and carry risks of tolerance, addiction, cognitive impairment, and falls. 1

Avoid typical antipsychotics (haloperidol, fluphenazine, thiothixene) as first-line therapy—they are associated with 50% risk of tardive dyskinesia after 2 years of continuous use in elderly patients. 1

Avoid cholinesterase inhibitors for treating agitation—they should not be newly prescribed to prevent or treat agitation and have been associated with increased mortality. 1

Monitoring Requirements

• Use quantitative measures (Cohen-Mansfield Agitation Inventory or NPI-Q) to establish baseline severity and monitor treatment response. 1
• Reassess at every visit—review the need for continued medication and attempt taper if symptoms are controlled. 1
• Monitor for side effects—including falls, sedation, metabolic changes, cognitive worsening, and (if using antipsychotics) extrapyramidal symptoms and QT prolongation. 1

Common Pitfalls to Avoid

• Do not add medications without first treating reversible medical causes—pain, infection, and metabolic disturbances must be addressed. 1
• Do not skip non-pharmacological interventions—they have substantial evidence for efficacy without mortality risks. 1
• Do not continue medications indefinitely—approximately 47% of patients continue receiving psychotropics after discharge without clear indication. 1
• Do not use antipsychotics for mild agitation—reserve them for severe symptoms that are dangerous or cause significant distress. 1