How does Rexulti (brexpiprazole) improve major depressive disorder?

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Last updated: April 19, 2025View editorial policy

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From the FDA Drug Label

The mechanism of action of brexpiprazole in the adjunctive treatment of major depressive disorder or treatment of schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.

The exact mechanism by which Rexulti (brexpiprazole) improves depression is unknown. However, it is believed that its efficacy may be mediated through a combination of:

  • Partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors
  • Antagonist activity at serotonin 5-HT2A receptors 1

From the Research

Rexulti (brexpiprazole) improves depression by working as an adjunctive treatment alongside antidepressants in patients with major depressive disorder who haven't responded adequately to antidepressant therapy alone, as evidenced by a recent study 2 that highlights its efficacy and safety profile.

Mechanism of Action

Rexulti functions as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors, while also acting as an antagonist at serotonin 5-HT2A receptors. This unique mechanism helps modulate neurotransmitter activity in the brain, particularly serotonin and dopamine, which are crucial for mood regulation.

Dosage and Administration

Rexulti is typically prescribed at a starting dose of 0.5 or 1 mg once daily, gradually increasing to the target dose of 2-3 mg daily based on individual response and tolerability, as supported by studies such as 3 and 4. Patients should take it at the same time each day with or without food.

Efficacy and Safety

Improvement may take several weeks, and the medication should be continued even after feeling better. Common side effects include weight gain, akathisia (restlessness), and increased risk of suicidal thoughts in young adults, as noted in studies like 5 and 6. Regular follow-up appointments are essential to monitor effectiveness and adjust dosage if needed.

Key Points

  • Rexulti is used as an adjunctive treatment for major depressive disorder
  • It has a unique mechanism of action involving serotonin and dopamine modulation
  • The typical dosage starts at 0.5 or 1 mg once daily and can be increased to 2-3 mg daily
  • Common side effects include weight gain and akathisia
  • Regular monitoring is necessary to adjust dosage and ensure safety and efficacy, as emphasized by the most recent and highest quality study 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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