What is the information about Rexulti (Brexpiprazole)?

From the Guidelines

Rexulti (brexpiprazole) is an atypical antipsychotic medication that is associated with a lower risk of weight gain compared to other antipsychotics, making it a preferable option for patients with weight concerns. According to the study published in Gastroenterology 1, antipsychotics such as lurasidone, ziprasidone, and aripiprazole are considered to be weight-neutral, with brexpiprazole also demonstrating a similar profile. The typical starting dose for depression is 0.5-1 mg once daily, which can be gradually increased to 2-3 mg daily. For schizophrenia, treatment usually begins at 1 mg daily and may be increased to 2-4 mg daily.

Key Points to Consider

• Rexulti works by modulating dopamine and serotonin receptors in the brain, helping to balance neurotransmitters that affect mood and thinking.
• Common side effects include weight gain, akathisia (restlessness), and increased blood sugar or cholesterol levels.
• Patients should take Rexulti at the same time each day with or without food and should not abruptly stop taking it without medical supervision.
• It may take several weeks to experience the full therapeutic benefits.
• Regular monitoring of metabolic parameters is important while on this medication.
• Patients should inform their doctor about all other medications they're taking, as Rexulti can interact with many drugs, particularly those affecting liver enzymes that metabolize the medication.

Important Considerations for Patients with Weight Concerns

• Antipsychotics such as olanzapine, clozapine, quetiapine, and risperidone are consistently associated with weight gain, and switching to a weight-neutral option like brexpiprazole may be beneficial for patients with weight concerns.
• The choice of antipsychotic medication should be guided by the individual patient's circumstance, taking into account their medical history, current medications, and potential side effects.
• As noted in the study 1, other antihypertensive medications that are considered weight-neutral include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel blockers, which may be beneficial for patients with obesity and hypertension.

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 (3)

CONTRAINDICATIONS Known hypersensitivity to brexpiprazole tablets or any of its components. (4)

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). (5.3) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. (5.4) Tardive Dyskinesia: Discontinue if clinically appropriate. (5.5) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain. (5.6) Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation. (5.7) 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. Consider discontinuing brexpiprazole if a clinically significant decline in WBC occurs in absence of other causative factors. (5.8) 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. (5.9) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. (5.11) Potential for Cognitive and Motor Impairment: Use caution when operating machinery. (5.14)

ADVERSE REACTIONS Most common adverse reactions in adults were (6.1): 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: Brexpiprazole is available in tablet form with strengths of 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg.
• Contraindications: Brexpiprazole is contraindicated in patients with known hypersensitivity to brexpiprazole or any of its components.
• Warnings and precautions: Brexpiprazole has several warnings and precautions, including increased risk of cerebrovascular adverse reactions, neuroleptic malignant syndrome, tardive dyskinesia, metabolic changes, and others.
• Adverse reactions: The most common adverse reactions in adults include weight increase, somnolence, and akathisia for MDD, and weight increase for schizophrenia. 2

From the Research

Overview of Rexulti (Brexpiprazole)

• Brexpiprazole, marketed as Rexulti, is an antipsychotic medication approved for the treatment of schizophrenia and as an adjunctive treatment for major depressive disorder 3, 4, 5.
• 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, 5.

Efficacy in Schizophrenia

• Brexpiprazole has demonstrated superiority over placebo in two 6-week, Phase 3 randomized controlled trials in acute schizophrenia, with a number needed to treat (NNT) of 7 3.
• In a 52-week, randomized withdrawal study, brexpiprazole significantly delayed the time to relapse compared with placebo, resulting in an NNT of 4 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 has been approved as an adjunctive treatment for major depressive disorder, with an NNT of 12 for response and 17-31 for remission vs placebo 6.
• Brexpiprazole appears to be a viable option for adjunctive treatment of major depressive disorder in patients who showed an inadequate response to 1 to 3 antidepressants 7.

Safety and Tolerability

• The most commonly encountered adverse event is increased weight, with short-term weight gain appearing modest 3.
• Rates of akathisia as an adverse event were lower compared to those with aripiprazole and cariprazine 6.
• 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.