A Review of the Efficacy and Saftey of using Rexulti® in treating Agitation in Alzheimer's Patients

 

Rexulti (brexpiprazole) was recently also studied for agitation associated with Alzheimer’s dementia, which is different from its use in depression or schizophrenia. It is not approved for memory or cognition — its role is specifically for managing agitation. Because of its increased risk of death, guidelines recommend Rexulti only when agitation is severe, distressing, and non-drug approaches have not worked. Here’s a clear overview of the non-drug (behavioral and environmental) strategies that are recommended before starting medications like Rexulti:

 

 

Care Pathway for Agitation with Dementia

 

Step 1: Identify Triggers (Always Start Here)

 

  • Look for causes of agitation: pain, hunger, constipation, infection, noise, overstimulation, or boredom.

 

  • Treat or remove the trigger whenever possible.

 

 

Step 2: Try Non-Drug Strategies First

 
Environmental Adjustments
  • Calm, consistent surroundings

 

  • Reduce noise and clutter

 

  • Good lighting, especially in the evening

 

 

Communication Approaches
  • Speak calmly and simply

 

  • Validate feelings, avoid arguing

 

  • Redirect with reassurance

 

 

Daily Activities & Engagement
  • Gentle exercise (walking, stretching)

 

  • Music, art, or simple household tasks

 

  • Safe sensory stimulation (aromatherapy, pet therapy, tactile items)

 

 

Comfort & Routine
  • Predictable schedule for meals, rest, and toileting

 

  • Massage, touch therapy, or calming rituals

 

  • Provide snacks and hydration regularly

 

 

Step 3: Evaluate Response

 

  • If agitation improves → continue non-drug strategies.

 

  • If agitation is mild but manageable → keep monitoring and adjusting environment.

 

  • If agitation is severe, dangerous, or causes major distress despite trying non-drug approaches → consider medication.

 

 

Step 4: Consider Medication (Last Resort)

 

  • Used only when non-drug methods fail and agitation poses a risk to patient or caregivers.

 

  • Options include antipsychotics such as Rexulti.

 

  • Always weigh benefit vs. risk

 

 

Step 5: Monitor & Reassess

 

  • If a medication is started, use the lowest effective dose.

 

  • Reassess regularly — can the drug be reduced or stopped later?

 

  • Continue non-drug supports even while on medication.

 

 

Rexulti in Alzheimer’s Patients (Agitation)

 

Rexulti was approved in 2023 for the treatment of agitation in Alzheimer’s dementia. Clinical trials showed that patients receiving Rexulti had significantly greater reductions in agitation scores (measured by the Cohen-Mansfield Agitation Inventory).

 

 

HOW LARGE WAS TREATMENT EFFECT?
  • Effects are considered modest, but agitation can be very distressing for both patients and caregivers, so even small improvements are meaningful.

 

number needs to treat (nnt)

  • About 1 in 7–8 patients taking Rexulti show meaningful improvement in agitation compared with placebo.

 

How soon can namzaric's effects start?
  • Some patients show early calming effects in the first 1–2 weeks, but the main benefit becomes clear by 4–6 weeks.

 

Number Needed to Harm (NNH)
  • The NNH, which estimates how many patients need to be treated before one experiences a significant adverse effect. About 1 in 15-20 people taking Rexulti experience side effects of weight gain, sleepiness, and restlessness 

 

  • Like all antipsychotics, Rexulti carries a boxed warning:
    • Increased risk of death in elderly patients with dementia-related psychosis. Most deaths are due to cardiovascular events (e.g., stroke, heart attack) or infections (e.g., pneumonia).

    •  This risk is thought to be similar across all atypical antipsychotics.

 

in summary
  • Rexulti can reduce agitation in about 1 in 7–8 patients.

 

  • Improvements are usually noticeable by 1 month.

 

  • Risks are real, including increased mortality in elderly dementia patients, so careful monitoring and discussion of risks vs. benefits with families and caregivers is essential.

 

  • It is not approved for memory or cognition — its role is specifically for managing agitation.

 

 

 

What is the general benefit: risk ratio when considering atypical antipsychotics for agitation if dementia patients? 

 

When considering atypical antipsychotics (like risperidone, olanzapine, quetiapine, aripiprazole) for psychosis or behavioral symptoms in dementia, the key concern is increased risk of harm.

 

Here’s what the data show on NNH (Number Needed to Harm):

 

Mortality Risk

Large meta-analyses (e.g., Schneider et al., NEJM 2005; FDA pooled data) found about a 1.6–1.7-fold increased risk of death in elderly dementia patients taking atypical antipsychotics compared with placebo.

Absolute risk increase ≈ 3–4% over 10–12 weeks.

 

That translates to a NNH ≈ 25–30 → meaning for every 25–30 dementia patients treated with an atypical antipsychotic for ~10–12 weeks, 1 extra death occurs compared to placebo.

 

Stroke Risk

Risk of cerebrovascular adverse events (stroke, TIA) is also increased.

Absolute risk increase ≈ 1–2%.

NNH ≈ 50–100 over ~10 weeks.

 

Symptom Benefit (for context)

Effect size is modest: about 18% improve on drug vs 10% on placebo (Cochrane, 2021).

So NNT ≈ 12 for symptomatic benefit.

 

Summary for caregivers

NNT for benefit: ~12 (some reduction in aggression/psychosis).

NNH for death: ~25–30.

NNH for stroke: ~50–100.

 

This is why guidelines recommend only using antipsychotics in dementia when symptoms are severe, dangerous, or distressing, and always for the shortest possible time after non-drug approaches fail.