Clinical Overview
Brexpiprazole is an atypical antipsychotic indicated for schizophrenia and as adjunctive treatment for major depressive disorder. It acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors while antagonizing 5-HT2A receptors, potentially offering efficacy with reduced side effects compared to full dopamine antagonists.
Primary Clinical Applications
Brexpiprazole is indicated for treatment of schizophrenia in adults and as adjunctive therapy to antidepressants for major depressive disorder when patients have inadequate response to antidepressant monotherapy. Its balanced receptor profile may provide benefits for both positive and negative symptoms of schizophrenia.
Mechanism and Clinical Benefits
Brexpiprazole’s partial agonist activity at dopamine D2 receptors provides “functional selectivity,” potentially offering antipsychotic efficacy while minimizing extrapyramidal side effects and prolactin elevation. The 5-HT1A partial agonism may contribute to antidepressant and cognitive benefits.
Clinical Considerations
The medication has a long half-life (91 hours) allowing for once-daily dosing but requiring consideration when discontinuing or switching medications. It generally has a favorable metabolic profile compared to many other atypical antipsychotics, with lower risk of significant weight gain or metabolic disturbances.
Prescribing Information
Dosing & Administration
Schizophrenia – Adults:
- Initial: 1 mg once daily for days 1-4
- Days 5-7: 2 mg once daily
- Days 8-14: 4 mg once daily
- Target dose: 2-4 mg once daily
- Range: 1-4 mg once daily
Major Depressive Disorder (Adjunctive) – Adults:
- Initial: 0.5-1 mg once daily
- Titration: May increase weekly by 0.5-1 mg
- Target dose: 2 mg once daily
- Range: 0.5-3 mg once daily
CYP2D6 Poor Metabolizers:
- Reduce dose by 50% for all indications
Administration:
- Take once daily with or without food
- Same time each day
- Long half-life allows flexibility in timing
Indications
- Treatment of schizophrenia in adults
- Adjunctive treatment of major depressive disorder in adults
Contraindications
- Known hypersensitivity to brexpiprazole or any component
- No absolute contraindications
Warnings & Precautions
- Boxed Warning: Increased mortality in elderly patients with dementia-related psychosis; increased suicidal thoughts in children, adolescents, and young adults (when used for depression)
- Neuroleptic malignant syndrome: Rare but serious risk
- Tardive dyskinesia: Risk with long-term use
- Metabolic changes: Monitor glucose, lipids, and weight
- Orthostatic hypotension: Monitor blood pressure
- Seizures: Use caution in patients with seizure history
Drug Interactions
- Strong CYP3A4 inhibitors: Reduce brexpiprazole dose by 50%
- Strong CYP2D6 inhibitors: Reduce brexpiprazole dose by 50%
- Strong CYP3A4 inducers: Double the brexpiprazole dose
- Combined strong inhibitors: Reduce dose by 75%
Adverse Reactions
Schizophrenia – Common (≥5%):
- Weight gain, akathisia, tremor, sedation
Depression (Adjunctive) – Common (≥5%):
- Weight gain, akathisia, tremor, somnolence
- Restlessness
Metabolic:
- Generally lower risk of significant metabolic effects compared to other antipsychotics
Special Populations
- CYP2D6 poor metabolizers: Reduce dose by 50%
- Hepatic Impairment: No dose adjustment for mild-moderate impairment
- Renal Impairment: No dose adjustment for mild-moderate impairment
- Elderly: Increased mortality risk in dementia-related psychosis
- Pregnancy: Category C – use only if benefits outweigh risks
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.
