Brexpiprazole
Rexulti
Second-Generation Antipsychotic (Partial D2 Agonist)Generic availableTDM data
The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT 1A and dopamine D 2 receptors, and antagonist activity at serotonin 5-HT 2A receptors.
Compare Brexpiprazole →FDA-Approved Indications
- Schizophrenia (adults; adolescents 13+)
- MDD — adjunct to antidepressants (adults)
- Agitation associated with Alzheimer's dementia (adults)
Common Off-Label Uses
- PTSD (adjunct)
- Bipolar disorder
What Sets This Drug Apart
- D2 partial agonist related to aripiprazole but with lower intrinsic D2 activity and stronger 5-HT1A/5-HT2A/alpha-1 binding — may offer better akathisia tolerability vs aripiprazole
- FDA-approved for adjunctive treatment of MDD (with antidepressant) and for schizophrenia — one of few SGAs with an MDD adjunct indication
- Very long half-life (~91 hours) — steady state requires 10-12 days; clinical effects of dose changes are slow to manifest
- Dose reduction required for CYP2D6 poor metabolizers (halve usual dose) and with strong CYP2D6 or CYP3A4 inhibitors; dual substrate
- Prolactin, QTc, and anticholinergic burden all near placebo levels; favorable metabolic profile at MDD adjunct doses
- Pathological gambling and impulse-control behaviors possible (shared D2 partial-agonist class effect with aripiprazole and cariprazine)
Boxed Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS Increased Mortality in