BLACK BOX WARNING
- increased mortality in elderly patients with dementia-related psychosis
- suicidal thoughts and behaviors (as adjunct antidepressant in pediatric and young adult patients)
brexpiprazole
Brand: Rexulti
⚠ BBW Beers Criteria Prototype: aripiprazole
Drug Class: second-generation antipsychotic (SGA)
Drug Family: antipsychotic
Subclass: serotonin-dopamine activity modulator (SDAM)
Organ Systems: cns
Mechanism of Action
Structural analog of aripiprazole with similar partial agonism at D2 and 5-HT1A receptors, but greater 5-HT2A antagonism and alpha-1 blockade. The balanced partial agonism produces antipsychotic effects with lower EPS risk and may enhance serotonergic neurotransmission relevant to adjunct antidepressant use.
D2 dopamine receptor (partial agonist)D3 receptor (partial agonist)5-HT1A receptor (partial agonist)5-HT2A receptor (antagonist)alpha-1 adrenergic receptor
Indications
- schizophrenia
- adjunct to antidepressants for major depressive disorder
- agitation associated with Alzheimer's dementia (FDA-approved 2023)
Contraindications
- no absolute contraindications (beyond hypersensitivity)
Adverse Effects
Common
- weight gain
- somnolence
- akathisia (lower than FGAs)
- headache
Serious
- NMS
- tardive dyskinesia
- metabolic effects
- impulse control disorders
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~95%; food has minimal effect |
| Distribution | protein binding >99%; Vd ~1.56 L/kg |
| Metabolism | primarily CYP2D6 and CYP3A4 |
| Excretion | fecal (~46%) and renal (~25%) |
| Half-life | 91 hours |
| Onset | several days to weeks |
| Peak | 4 hours |
| Duration | once-daily dosing |
| Protein Binding | >99% |
| Vd | 1.56 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP2D6 inhibitors (fluoxetine, paroxetine) | increase brexpiprazole exposure; reduce dose by 50% | major |
| strong CYP3A4 inhibitors | increase brexpiprazole exposure; reduce dose by 50% | major |
| strong CYP3A4 inducers | decrease brexpiprazole levels; double dose | major |
Nursing Considerations
- Monitor weight and metabolic parameters (glucose, lipids) at baseline and quarterly; brexpiprazole causes moderate weight gain.
- As an adjunct antidepressant, assess for suicidal ideation in children, adolescents, and young adults per the antidepressant BBW.
- Dose reduction required with concurrent CYP2D6 or CYP3A4 inhibitors; verify the complete medication list before administration.
- Brexpiprazole was approved in 2023 for Alzheimer's-related agitation with improved evidence versus risperidone for this indication; monitor for falls and orthostatic hypotension in this population.
Clinical Pearls
- Brexpiprazole represents the second FDA approval of a dopamine partial agonist (after aripiprazole) with comparable efficacy but potentially improved tolerability in the adjunct antidepressant role.
- Its FDA approval for agitation in Alzheimer's dementia (2023) is notable because all antipsychotics still carry the dementia-related psychosis BBW — brexpiprazole is the only one with positive Phase III data specifically for this indication.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.