What is brexpiprazole (Rxulti)?

From the Guidelines

Brexpiprazole is a third-generation antipsychotic medication, classified alongside aripiprazole, cariprazine, and lumateperone, used in the treatment of schizophrenia and as an adjunct for major depressive disorder. According to the most recent evidence available, as outlined in a systematic review and synthesis of 489 studies investigating treatments for negative symptoms in the schizophrenia spectrum 1, brexpiprazole falls under the category of pharmacological interventions with standard antipsychotics.

Key Characteristics of Brexpiprazole

• It is primarily used to treat schizophrenia and as an add-on treatment for major depressive disorder.
• The medication affects certain neurotransmitters in the brain, particularly dopamine and serotonin.
• For schizophrenia, the typical starting dose is 1 mg once daily, which can be gradually increased to the recommended target dose of 2-4 mg daily.
• When used as adjunctive therapy for depression, it usually starts at 0.5-1 mg daily and may be increased to 2-3 mg daily.

Side Effects and Considerations

• Common side effects include weight gain, akathisia (restlessness), and sedation.
• The medication should be taken consistently, with or without food.
• Patients should be monitored for metabolic changes, movement disorders, and other potential adverse effects.
• It may take several weeks to experience the full therapeutic benefits.
• Patients should not stop taking brexpiprazole abruptly without consulting their healthcare provider, as this could lead to withdrawal symptoms or worsening of the underlying condition.

Clinical Use

Brexpiprazole's balanced receptor profile may result in fewer side effects compared to some other antipsychotics, making it a valuable option for patients with schizophrenia or major depressive disorder. As with any antipsychotic medication, careful consideration of the benefits and risks, as well as regular monitoring, is crucial for optimal patient outcomes. The decision to prescribe brexpiprazole should be based on the individual patient's needs and medical history, taking into account the latest clinical guidelines and evidence, such as that provided by the systematic review 1.

From the FDA Drug Label

Brexpiprazole, an atypical antipsychotic, is available as brexpiprazole tablets. Brexpiprazole is 7-{4-[4-(1-Benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one.

Brexpiprazole is an atypical antipsychotic.

• It is available as oral tablets in various strengths.
• The chemical structure of brexpiprazole is defined by its molecular formula: C25H27N3O2S.
• Its molecular weight is 433.57 g/mol 2 2

From the Research

Definition and Mechanism of Action

• Brexpiprazole is an antipsychotic medication that acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A and at adrenergic alpha1B and alpha2C receptors 3.
• It is a serotonin-dopamine activity modulator, which suggests a more tolerable side effect profile with regard to akathisia, extrapyramidal dysfunction, and sedation 4.

Clinical Uses

• Brexpiprazole is approved for the treatment of schizophrenia and as an adjunctive treatment in major depressive disorder 3, 4, 5, 6, 7.
• It has been shown to be effective in reducing symptoms of schizophrenia and major depressive disorder, with a number needed to treat (NNT) of 6-15 for response in acute schizophrenia treatment and 4 for maintenance 4.
• Brexpiprazole can also be effective as an adjunctive therapy in patients with major depressive disorder who have anxiety symptoms, reducing anxiety symptoms 6.

Dosage and Administration

• The recommended dose range of brexpiprazole for the treatment of schizophrenia is 2-4 mg/day, and for major depressive disorder, it is 2 mg/day 3, 4, 5.
• The recommended titration schedule is to start with 1 mg/day and increase to 2 mg/day on Day 5 to Day 7, then to 4 mg/day on Day 8 3.
• Dose adjustments should be considered in hepatic or renal dysfunction and/or in poor cytochrome P450 2D6 metabolizers 4.

Safety and Tolerability

• Brexpiprazole is generally well tolerated, with a lower risk of akathisia and extrapyramidal symptoms compared to other antipsychotics 4, 5.
• Common adverse events include increased weight, akathisia, and sedation, but the risk of these events is relatively low 3, 4, 5.
• Brexpiprazole has a minimal effect on prolactin levels and no clinically relevant effects on the ECG QT interval 3, 5.