Section 05 · Monograph

Brexpiprazole

Reviewed Nov 2026FDA label

RexultiAtypical antipsychotic

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis treated with antipsychotic drugs (~1.6-1.7x placebo), largely from cardiovascular events or infections; not approved for dementia-related psychosis outside the specific Alzheimer's agitation indication
Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (up to age 24) with MDD and other psychiatric disorders; monitor closely, especially during initial months and after dose changes; not approved for pediatric MDD

Adjunctive treatment to antidepressants for major depressive disorder (MDD) in adultsFDA-labeled
Treatment of schizophrenia in adults and pediatric patients 13 years of age and olderFDA-labeled
Treatment of agitation associated with dementia due to Alzheimer's disease (not intended for PRN use)FDA-labeled

Serotonin-dopamine activity modulator (SDAM), mechanistically distinct from typical and other atypical antipsychotics
Partial agonist at serotonin 5-HT1A and dopamine D2 receptors
Antagonist at serotonin 5-HT2A receptors and at noradrenergic alpha-1B and alpha-2C adrenergic receptors
The balance of partial agonism at D2/5-HT1A with 5-HT2A antagonism is thought to underlie efficacy across mood, psychotic, and agitation symptoms with a comparatively favorable akathisia/EPS profile

MDD (adjunctive, adults): initiate at 0.5-1 mg once daily; titrate weekly to a target dose of 2 mg once daily; maximum 3 mg once daily
Schizophrenia (adults): initiate at 1 mg once daily days 1-4; increase to 2 mg days 5-7; increase to 4 mg starting day 8 as tolerated; target range 2-4 mg once daily
Agitation associated with Alzheimer's dementia: initiate at 0.5 mg once daily for 1 week; increase to 1 mg once daily for 1 week; then increase to a target dose of 2 mg once daily; may increase further to a maximum of 3 mg once daily after at least 2 weeks
Dosage adjustments required for CYP2D6/CYP3A4 inhibitor or inducer co-administration
Administer once daily without regard to meals

Moderate-to-severe hepatic or renal impairment: reduce maximum dose to 2 mg/day for MDD and Alzheimer's agitation, 3 mg/day for schizophrenia

Known hypersensitivity to brexpiprazole or to any excipients; reactions have included rash, facial swelling, urticaria, and anaphylaxis

Strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine): reduce dose to half the usual dose
Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin): reduce dose to half the usual dose
Combined strong CYP2D6 and CYP3A4 inhibitors: reduce dose to one-quarter of usual dose
Known CYP2D6 poor metabolizers: reduce dose to half the usual dose
Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin): approximately double the dose over 1-2 weeks
Concomitant CNS depressants (benzodiazepines, opioids, alcohol) may increase sedation and fall risk, particularly in elderly dementia patients
Additive antihypertensive effect possible with antihypertensive medications (orthostatic hypotension risk)

Weight gain
Akathisia
Somnolence
Headache, nasopharyngitis, dizziness, urinary tract infection (Alzheimer's agitation indication)
Class-related risks: tardive dyskinesia, neuroleptic malignant syndrome, metabolic changes (hyperglycemia, dyslipidemia), orthostatic hypotension/syncope, leukopenia/neutropenia/agranulocytosis, seizures
Pathological gambling and other compulsive behaviors (impulse-control disorders)
Increased mortality and cerebrovascular adverse events when used off-label in elderly dementia-related psychosis outside the Alzheimer's agitation indication

Baseline and periodic metabolic monitoring: fasting glucose/HbA1c, lipid panel, and weight
Monitor for extrapyramidal symptoms, akathisia, and signs of tardive dyskinesia
Monitor for neuroleptic malignant syndrome
CBC monitoring in patients with pre-existing low WBC or history of drug-induced leukopenia/neutropenia
Orthostatic vital signs, particularly in elderly patients
Screen for new-onset compulsive behaviors
Monitor for suicidal ideation/behavior when used for MDD
Cardiovascular and infection risk assessment in elderly dementia patients given black box mortality warning

Third-trimester exposure to antipsychotics may cause extrapyramidal and/or withdrawal symptoms in neonates
There is a pregnancy exposure registry that monitors outcomes in women exposed to atypical antipsychotics
Available data have not established a clear drug-associated risk of major birth defects or miscarriage
Animal reproduction studies showed adverse developmental effects at maternally toxic doses
No data on presence in human milk, effects on milk production, or effects on the breastfed infant