Is Rexulti (brexpiprazole) exclusively used for treating dementia?

Is Rexulti Only for Dementia?

No, Rexulti (brexpiprazole) is not only for dementia—it is FDA-approved for schizophrenia and as adjunctive treatment for major depressive disorder in adults, and it carries a black box warning explicitly stating it is NOT approved for dementia-related psychosis due to increased mortality risk. 1

FDA-Approved Indications

Brexpiprazole has two primary FDA-approved uses:

• Schizophrenia treatment in adults, with recommended dosing starting at 1 mg daily and titrating to a target of 2-4 mg daily 1, 2
• Adjunctive treatment for major depressive disorder (MDD) in adults, with recommended dosing starting at 0.5-1 mg daily and titrating to a target of 2 mg daily (maximum 3 mg daily) 1, 2

Critical Black Box Warning for Dementia

Brexpiprazole carries an FDA black box warning that it is NOT approved for treating patients with dementia-related psychosis because elderly patients with dementia-related psychosis treated with antipsychotic drugs have a 1.6-1.7 times increased risk of death compared to placebo. 1

• Deaths in dementia patients on antipsychotics are primarily cardiovascular (heart failure, sudden death) or infectious (pneumonia) in nature 1
• The drug-treated death rate was approximately 4.5% versus 2.6% in placebo groups over 10-week trials 1
• Brexpiprazole also increases risk of cerebrovascular adverse events including stroke in elderly dementia patients 1

Recent Approval for Agitation in Alzheimer's Dementia

Despite the black box warning, brexpiprazole was recently approved (post-2023) specifically for agitation associated with dementia due to Alzheimer's disease at doses of 2-3 mg daily—making it the first and only FDA-approved pharmacologic agent for this specific indication. 3, 4

• This represents an important regulatory precedent as the first approval for any neuropsychiatric syndrome of Alzheimer's disease 3
• Clinical trials showed approximately 5-point greater reduction on the Cohen-Mansfield Agitation Inventory compared to placebo at week 12 4
• Brexpiprazole should be used as a maintenance medication for agitation, NOT as a PRN or "as needed" treatment 4
• The black box warning for increased mortality in dementia-related psychosis still applies to this indication 3, 4

Important Clinical Caveats

Common pitfalls to avoid:

• Do not confuse the agitation indication with general dementia treatment—brexpiprazole is not approved for cognitive symptoms, behavioral problems, or psychosis in dementia outside of the specific agitation indication 3, 4
• The agitation indication is narrow—it applies only to agitation associated with dementia due to Alzheimer's disease, not other dementia types 3, 4
• Post-marketing surveillance is critical to understanding the true safety profile given the mortality concerns 3
• There is ongoing debate about whether the statistically significant agitation score reductions translate to clinically meaningful differences 4
• No head-to-head trials exist comparing brexpiprazole to other antipsychotics for agitation 4

Guideline-Recommended Dementia Treatments

For general dementia management, guidelines recommend entirely different medications:

• Cholinesterase inhibitors (donepezil, galantamine, rivastigmine) are first-line for mild to moderate Alzheimer's disease 5, 6
• Memantine is recommended for moderate to severe dementia 5, 6
• Atypical antipsychotics like brexpiprazole should be avoided for general behavioral problems in dementia due to the FDA black box warning and should be tapered when possible 5