Rexulti (Brexpiprazole) Indication Specificity
Rexulti (brexpiprazole) is FDA-approved specifically and exclusively for agitation associated with dementia due to Alzheimer's disease—it is NOT approved for agitation in other types of dementia such as vascular dementia, Lewy body dementia, frontotemporal dementia, or Parkinson's disease dementia. 1, 2
FDA Approval Scope
- Brexpiprazole received FDA approval as the first and only pharmacologic agent specifically indicated for agitation associated with dementia due to Alzheimer's disease 1, 2
- This represents a landmark regulatory precedent as the first approval for treatment of any neuropsychiatric syndrome specifically in Alzheimer's disease 2
- The approval is based on Phase 2/3 and Phase 3 clinical trials that enrolled only patients with agitation in Alzheimer's dementia, not other dementia subtypes 2, 3
Clinical Trial Population
- All pivotal trials (NCT01862640, NCT01922258, NCT03548584) specifically enrolled patients with agitation associated with dementia due to Alzheimer's disease 3, 4
- The efficacy data demonstrating approximately 5-point greater reduction on the Cohen-Mansfield Agitation Inventory compared to placebo applies only to the Alzheimer's dementia population 1, 3
- No head-to-head trials or controlled studies have evaluated brexpiprazole in non-Alzheimer's dementias 1
Critical Distinction for Other Dementias
For agitation in Parkinson's disease dementia specifically, quetiapine (starting at 12.5 mg twice daily) is the preferred antipsychotic due to lower risk of extrapyramidal side effects, NOT brexpiprazole. 5
- Patients with Parkinson's disease dementia are extremely sensitive to extrapyramidal side effects from antipsychotics, making brexpiprazole inappropriate for this population 5
- For other dementia types (vascular, Lewy body, frontotemporal), brexpiprazole use would be off-label without supporting efficacy or safety data 1, 2
Practical Implications
- Brexpiprazole should only be prescribed when there is documented Alzheimer's disease as the underlying cause of dementia 1, 2
- The 2-3 mg/day dosing that showed efficacy in trials applies specifically to Alzheimer's dementia patients 3, 1
- Like all antipsychotics used in dementia, brexpiprazole carries a black box warning for increased mortality risk in elderly patients with dementia-related psychosis 2, 4
Common Pitfall to Avoid
Do not assume brexpiprazole can be used interchangeably for agitation across all dementia types—the FDA approval and all supporting evidence is limited exclusively to Alzheimer's disease dementia. 1, 2 For non-Alzheimer's dementias, traditional approaches using SSRIs as first-line or other atypical antipsychotics off-label (with appropriate informed consent about lack of evidence) remain the standard of care 6, 5