Rexulti (brexpiprazole) was  approved by the FDA in 2023 for treating agitation associated with Alzheimer’s dementia, but 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.

 

 

Weighing Rexulti's Pros and Cons 

 

NUMBER NEEDED TO TREAT (NNT)

 

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

 

• Effects are considered modest, but agitation can be very distressing for both patients and caregivers, so even small improvements are meaningful.

 

• Clinical trials shows patients receiving Rexulti has significantly greater reduction in agitation scores measured by Cohen-Mansfield Agitation Inventory.

 

 

HOW SOON CAN BREXPIPRAZOLE'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 (like risperidone, olanzapine, quetiapine, aripiprazole) for psychosis or behavioral symptoms in dementia,

 

• NNH for death: ~25–30 over 10–12 weeks, (Schneider et al., NEJM 2005; FDA pooled data) → meaning for every 25–30 dementia patients treated with an atypical antipsychotic for ~10–12 weeks, 1 extra death occurs compared to placebo.

   

• NNH for stroke: ~50–100 over ~10 weeks.