Second-generation (atypical) antipsychotic
Partial agonist at dopamine D2 and serotonin 5-HT1A receptors; antagonist at serotonin 5-HT2A and 5-HT2B receptors; may enhance prefrontal glutamatergic transmission via a dopamine D1 receptor-dependent mechanism
Schizophrenia, adjunctive treatment of major depressive disorder (MDD), agitation associated with dementia due to Alzheimer’s disease (AD)
Behavioral disturbances in traumatic brain injury (TBI), irritability and aggression in intellectual disability
Oral tablets (0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg)
0.5–1 mg p.o. daily; titrate every 1–2 weeks as tolerated
0.5–3 mg/day (for MDD adjunct or agitation in dementia); up to 4 mg/day for schizophrenia
Half-life ~91 hours; metabolized via CYP3A4 and CYP2D6; steady state reached in ~10–12 day
Weight gain, akathisia, somnolence, fatigue, agitation
Extrapyramidal symptoms (EPS), impulse control disorders, neuroleptic malignant syndrome (NMS), orthostatic hypotension
Monitor weight, fasting glucose, lipids, and EPS every 3–6 months; consider behavioral monitoring for impulse dysregulation
Increased risk of mortality in elderly patients with dementia-related psychosis; increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD
Brexpiprazole may be preferred in patients at risk for metabolic complications due to its relatively favorable weight and metabolic profile compared to other antipsychotics. While FDA-approved for agitation in Alzheimer’s disease (AD), it still carries the class-wide warning for increased mortality in elderly patients with dementia-related psychosis and should be used cautiously. Preliminary evidence suggests it may reduce behavioral disturbances in patients with traumatic brain injury (TBI) or intellectual disability, though data remain limited. Clinicians should monitor for activation symptoms, including akathisia or agitation, and assess for impulse control problems, particularly in patients with a prior history of behavioral dysregulation.