brexpiprazole

Antipsychotic

Brands: REXULTI

Last reviewed 2025-09-23

Reviewed by PsychMed Editorial Team.

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Quick answers

What is brexpiprazole?
Brexpiprazole (brand Rexulti) is a second-generation (atypical) antipsychotic and dopamine-serotonin system stabilizer with lower intrinsic activity at D2 receptors than aripiprazole, designed to balance efficacy and tolerability.
What is REXULTI?
REXULTI is a brand name for brexpiprazole.
What is REXULTI (brexpiprazole) used for?
Label indications include: Schizophrenia; adjunctive therapy to antidepressants for major depressive disorder.
What drug class is REXULTI (brexpiprazole)?
Antipsychotic.
What is the mechanism of action of REXULTI (brexpiprazole)?
D2/D3 partial agonist; 5‑HT1A partial agonist; 5‑HT2A antagonist.
What strengths does REXULTI (brexpiprazole) come in?
Oral tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg (scored for flexible titration).
Is REXULTI (brexpiprazole) a controlled substance?
No — it is not scheduled as a controlled substance under U.S. federal law.
What is REXULTI (brexpiprazole) dosing for schizophrenia?
Schizophrenia (adults): titrate from 1 mg once daily (days 1–4) to 2 mg (days 5–7), then 4 mg once daily; therapeutic range 2–4 mg/day.
What is the maximum dose of REXULTI (brexpiprazole) for major depressive disorder (clinical depression)?
Adjunctive major depressive disorder: initiate 0.5 mg once daily with antidepressant, increase to 1 mg after ≥1 week, then 2 mg/day; some patients require 3 mg/day (max 3 mg).

Snapshot

Class: Antipsychotic
Common US brands: REXULTI
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-09-23

Label indications

Schizophrenia; adjunctive therapy to antidepressants for major depressive disorder.

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Clinical Highlights

Brexpiprazole (brand Rexulti) is a second-generation (atypical) antipsychotic and dopamine-serotonin system stabilizer with lower intrinsic activity at D2 receptors than aripiprazole, designed to balance efficacy and tolerability. This profile highlights its use in schizophrenia and in antidepressant augmentation regimens for treatment-resistant mood presentations within serious mental illness care pathways.

Clinicians select brexpiprazole for once-daily dosing, relatively low akathisia rates compared with aripiprazole, and modest metabolic burden. Weight gain and akathisia remain top adverse-event drivers, but its tolerability profile supports use in outpatient schizophrenia programs and antidepressant augmentation.
The compare table and brexpiprazole evidence feed can support shared decision-making with shared-care teams, and the brexpiprazole print page provides patient-friendly counseling materials.
Schizophrenia (adults) (FDA 2015)
Schizophrenia (adolescents 13–17) (FDA 2022)
Adjunctive treatment to antidepressants in major depressive disorder (adults) (FDA 2015)

Dosing & Formulations

Oral tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg (scored for flexible titration). Schizophrenia (adults): titrate from 1 mg once daily (days 1–4) to 2 mg (days 5–7), then 4 mg once daily; therapeutic range 2–4 mg/day.

Schizophrenia (adolescents 13–17): start 0.5 mg once daily, increase by 0.5–1 mg weekly to 2–4 mg/day per response and tolerability.
Adjunctive major depressive disorder: initiate 0.5 mg once daily with antidepressant, increase to 1 mg after ≥1 week, then 2 mg/day; some patients require 3 mg/day (max 3 mg).
Label recommends dose adjustments: halve dose with strong CYP3A4 or CYP2D6 inhibitors; quarter dose if combined inhibitors present; double dose gradually with strong CYP3A4 inducers.
Therapeutic drug monitoring is not standard; no established serum target range.

Monitoring & Risks

Boxed warning: Increased mortality in elderly patients with dementia-related psychosis (antipsychotic class warning). Boxed warning: Suicidal thoughts and behaviors in children, adolescents, and young adults treated with antidepressants (applies to adjunctive MDD indication).

Weight gain: ≥7% weight gain in ~10–18% of patients over 6 months; higher rates in MDD augmentation trials.
Akathisia: Occurs in ~9–14%, typically within first 2–3 weeks and dose-related.
Somnolence/sedation: Reported in ~7–12%; may necessitate evening dosing.
Headache: Approximately 10–12% of patients.

Drug Interactions

Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) or CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine, bupropion) increase exposure; label recommends reducing brexpiprazole dose by 50% (or to 25% of usual dose if both pathways are inhibited). Strong CYP3A4 inducers (carbamazepine, rifampin, St. John’s wort) lower exposure; label recommends doubling the brexpiprazole dose gradually over 1–2 weeks with efficacy monitoring.

Additive CNS depression with alcohol, benzodiazepines, opioids, or sedating antihistamines.
May diminish response to dopamine agonists such as levodopa; this combination is often avoided in Parkinson’s disease when dopaminergic therapy is needed.

Practice Notes

Long half-life supports once-daily adherence but prolongs titration and discontinuation; expectation-setting about delayed onset of effect (1–2 weeks) is helpful. Weight, fasting glucose, and lipids are typically checked at baseline, 3 months, and annually; more frequent checks are often used in MDD augmentation where metabolic effects are amplified.

Manage akathisia with dose adjustments, beta-blockers, or benzodiazepines; patients can be advised on early symptom recognition.
Renal impairment (CrCl <60 mL/min) or moderate hepatic impairment warrants maximum daily dose of 3 mg for schizophrenia and 2 mg for adjunctive MDD.
No routine ECG monitoring required, but a baseline tracing is often considered in patients with cardiac history or polypharmacy; the brexpiprazole print page can reinforce key points between visits.

References

REXULTI (brexpiprazole) prescribing information — Otsuka Pharmaceutical Co. (2024)
FDA Rexulti Medr 2015
Efficacy AND Safety OF Brexpiprazole FOR THE Treatment OF Acute Schizophrenia: A Randomized, Double Blind, Placebo Controlled Trial — Schizophrenia Research (2015)
Citrome2016 Brexpiprazole Review
Maeda2014 Brexpiprazole Characterization
AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)