What is the information about Rexulti (Brexpiprazole)?

From the Guidelines

Rexulti (brexpiprazole) is not mentioned in the provided evidence, however, based on the most recent and highest quality studies, it is an atypical antipsychotic medication primarily used to treat schizophrenia and as an add-on treatment for major depressive disorder (MDD) when antidepressants alone are not effective [@3@]. The provided evidence discusses the assessment and treatment of children and adolescents with bipolar disorder, and mentions several atypical antipsychotics such as quetiapine, aripiprazole, and risperidone, but does not include brexpiprazole 1. Key points to consider when prescribing Rexulti include:

• Starting dose and target dose, which are typically 1 mg once daily, gradually increasing to a target dose of 2-4 mg daily for schizophrenia, and 0.5-1 mg daily as an adjunct to antidepressants, with a target dose of 2 mg daily for depression [@3@].
• Common side effects, such as weight gain, akathisia (restlessness), headache, and insomnia, which should be monitored regularly [@3@].
• The importance of regular monitoring for metabolic changes (weight, blood sugar, cholesterol) while taking this medication [@3@].
• Patients should be aware that full benefits may take several weeks to develop, and the medication should not be stopped abruptly without medical supervision [@3@].

From the FDA Drug Label

DOSAGE FORMS AND STRENGTHS Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg CONTRAINDICATIONS Known hypersensitivity to brexpiprazole tablets or any of its components. WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. Tardive Dyskinesia: Discontinue if clinically appropriate. Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain. Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation. Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ADVERSE REACTIONS Most common adverse reactions in adults were MDD: Weight increased, somnolence and akathisia (≥ 5% and at least twice the rate for placebo). Schizophrenia: Weight increased (≥ 4% and at least twice the rate for placebo).

The information about Rexulti (Brexpiprazole) includes:

• Dosage forms and strengths: Tablets of 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg.
• Contraindications: Known hypersensitivity to brexpiprazole or its components.
• Warnings and precautions: Cerebrovascular adverse reactions, neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes, pathological gambling, leukopenia, orthostatic hypotension, seizures, and potential for cognitive and motor impairment.
• Adverse reactions: Weight increase, somnolence, akathisia, and others. 2

From the Research

Overview of Rexulti (Brexpiprazole)

• Brexpiprazole, marketed as Rexulti, is an antipsychotic medication approved by the U.S. Food and Drug Administration for the treatment of schizophrenia and as an adjunctive treatment for major depressive disorder 3, 4, 5, 6, 7.
• It acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A and adrenergic alpha1B and alpha2C receptors 3, 4, 5.

Efficacy in Schizophrenia

• Brexpiprazole has demonstrated superiority over placebo in two 6-week, Phase 3 randomized controlled trials in acute schizophrenia, with pooled responder rates of 46% for brexpiprazole 2-4 mg/day vs. 31% for placebo 3.
• In a 52-week, randomized withdrawal study, significantly fewer patients relapsed in the brexpiprazole group compared with placebo (13.5% vs. 38.5%) 3.
• Brexpiprazole 2-4 mg/day produced statistically significant and clinically meaningful improvements in overall symptomatology and psychosocial functioning compared with placebo in adults with acute exacerbation of schizophrenia 4.

Efficacy in Major Depressive Disorder

• Brexpiprazole is approved as an adjunctive treatment for major depressive disorder, with a number needed to treat (NNT) of 12 for response and 17-31 for remission vs placebo 5.
• Brexpiprazole target dosing is 2 mg in depression augmentation, with dose adjustments considered in hepatic or renal dysfunction and/or in poor cytochrome P450 2D6 metabolizers 5.

Safety and Tolerability

• The most commonly encountered adverse event is increased weight, with short-term weight gain appearing modest (approximately 10% of patients receiving brexpiprazole 1-4 mg/day gained ≥7% body weight from baseline) 3.
• Rates of akathisia as an adverse event were 5.5% for the pooled doses of brexpiprazole 1-4 mg/day vs. 4.6% for placebo, yielding a number needed to harm (NNH) of 112 3.
• Brexpiprazole was generally well tolerated, exhibiting an adverse event profile characterized by a relatively low incidence of activating and sedating adverse effects, small changes in QT interval and metabolic parameters that were not clinically significant, and moderate weight gain 4.