Brexpiprazole - Indications, Dosage, Precautions and Side Effects

Overview

Brexpiprazole belongs to the benzisoxazole class of compounds and has emerged as a notable player in the treatment of psychiatric disorders. Brexpiprazole is used to treat depression when symptoms cannot be controlled by the antidepressant alone. It is also prescribed for managing the symptoms of schizophrenia (mental illness leading to disturbed thinking and loss of interest in life) in adults and children 13 years of age and above. Brexpiprazole is also prescribed for treating agitation in people with dementia due to Alzheimer's disease (a brain disorder that gradually destroys memory, thinking, and the ability to handle daily activities).

Drug Group

Brexpiprazole belongs to the class of medications known as atypical antipsychotics. Atypical antipsychotics, also called second-generation antipsychotics, are a class of medications mainly used to treat psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder (as adjunctive treatment). These drugs are called "atypical" because they differ from first-generation antipsychotics in their receptor binding profiles, often resulting in a lower risk of certain side effects usually associated with older antipsychotic medications.

Dosage Forms and Available Strengths:

Brexpiprazole is primarily available in the form of oral tablets. The available strengths of Brexpiprazole tablets can vary depending on the country and the pharmaceutical manufacturer.

Common Strengths Include:

Brexpiprazole Tablets:

• 0.25 mg (milligrams).

• 0.5 mg.

• One mg.

• Two mg.

• Three mg.

• Four mg.

It is important to note that the specific dosages and formulations available may vary based on regional regulatory approvals and market conditions.

Warnings and Precautions:

It is essential to be aware that certain side effects associated with antipsychotic medications, including Brexpiprazole, can be serious. These may include:

• Suicidal Thoughts: Antidepressant medications, including Brexpiprazole, have been associated with a high risk of suicidal thoughts, especially in young adults.

• Neuroleptic Malignant Syndrome (NMS): A rare but potentially life-threatening condition characterized by hyperthermia (increased body temperature), severe muscle rigidity, altered mental status, and autonomic dysfunction.

• Tardive Dyskinesia: An involuntary movement disorder characterized by repetitive, purposeless movements, especially of the face.

• Metabolic Changes: Antipsychotic medications, including Brexpiprazole, may be associated with metabolic changes, including an increased risk of hyperglycemia (high blood sugar) and dyslipidemia (abnormal levels of lipids in the blood).

• Orthostatic Hypotension: This is caused by a sudden drop in blood pressure upon standing, which can lead to dizziness or fainting.

For Patients

What Is Depression?

Depression, also known as major depressive disorder (MDD), is a common and severe mental health condition that causes a persistent feeling of hopelessness, sadness, and a lack of interest in daily activities. Depression is a complex condition with multiple contributing factors. These can include a combination of genetic, biological, environmental, and psychological factors. Trauma, chronic stress, a family history of depression, and certain medical conditions can increase the risk of developing depression.

How Does Brexpiprazole Work?

Brexpiprazole is an atypical antipsychotic drug used for treating conditions such as schizophrenia and major depressive disorder (MDD). Its exact mechanism of action is not completely understood, but it is believed to involve interactions with neurotransmitter systems in the brain, particularly serotonin and dopamine.

1. Serotonin (5-HT) Receptors:

• Brexpiprazole is a partial agonist at serotonin 5-HT1A receptors. The partial agonist activity at these receptors is thought to enhance serotonin neurotransmission, which is associated with mood regulation.

• It also acts as an antagonist at serotonin 5-HT2A receptors. Antagonism at these receptors helps regulate serotonin levels and may contribute to mitigating side effects associated with excessive serotonin activity, such as anxiety and insomnia.

2. Dopamine (D) Receptors:

• Brexpiprazole works as a partial agonist at dopamine D2 receptors. Dopamine is a neurotransmitter that controls various functions, including mood and reward. The partial agonist activity at D2 receptors helps modulate dopamine levels, contributing to the antipsychotic effects of Brexpiprazole.

• The medication also exhibits partial agonist activity at dopamine D3 and D4 receptors, further influencing dopamine neurotransmission.

3. Noradrenergic Receptors:

• Brexpiprazole has antagonistic effects on noradrenergic alpha 1B and alpha 2C receptors. These receptors are part of the noradrenergic system, and their modulation contributes to the overall pharmacological effects of Brexpiprazole.

What Are the Clinical Uses of the Drug?

Its approval for schizophrenia and major depressive disorder (MDD) marked a significant milestone in the pursuit of improved therapeutic options for these conditions. To comprehend the intricacies of Brexpiprazole, it is imperative to explore its mechanism of action, pharmacokinetic properties, and clinical applications that have solidified its position in psychiatric care.

What Are the Side Effects of Brexpiprazole?

Brexpiprazole, like any medication, may cause side effects. It is essential to note that not all patients will have these side effects, and their severity might also vary. If one is prescribed Brexpiprazole, discussing potential side effects with the healthcare provider is imperative. Common side effects of Brexpiprazole might include:

• Akathisia: This condition leads to restlessness with a constant urge to move.

• Weight Gain: Some individuals may experience increased body weight while taking Brexpiprazole.

• Somnolence: This refers to a state of drowsiness or a strong desire to sleep.

• Fatigue: Individuals may experience a sense of tiredness or lack of energy.

• Nausea: Some people may experience nausea as a side effect of Brexpiprazole.

• Insomnia: While somnolence is a possible side effect, some individuals may also experience difficulty sleeping.

• Headache: Headaches are usually seen as a side effect of Brexpiprazole.

• Anxiety: Some individuals may experience increased anxiety or nervousness.

It is important to be aware that certain side effects associated with antipsychotic medications, including Brexpiprazole, can be serious.

Dietary Considerations:

• Caffeine and Stimulants: Brexpiprazole may cause somnolence (drowsiness) in some individuals. While caffeine consumption is a personal choice, it may be advisable to moderate caffeine intake, especially if excessive drowsiness is a concern.

• Alcohol: It is generally recommended to limit or avoid alcohol while taking antipsychotic medications. Alcohol can interact with these medications, potentially increasing sedation and impairing cognitive function.

Missed Dose:

In case of a missed dose, take it as soon as possible. However, the missed dose can be skipped if it is almost time for the next dose. Do not double doses.

Storage:

• Store the medicine in a capped container at room temperature, away from heat, direct light, and moisture.

• Keep from freezing.

• Keep away from children.

• Consult the healthcare provider about the disposal of any medicine that is not being used.

For Doctors

Indications:

• Brexpiprazole is prescribed as an adjunctive therapy to antidepressants for major depressive disorder (MDD) in adults.

• Schizophrenia in adults and pediatric patients (13 years and older).

Dosage:

The dose of this medicine will differ for different patients. Follow the doctor's advice. If the dose differs, it only changes after consulting with the doctor. The frequency of doses, the time interval between doses, and the duration for which the medicine is taken depend on the medical problem for which the medicine is prescribed.

For Oral Dosage Form (Tablets):

Depression:

• Adults - Initially, 0.5 or one milligrams (mg) once daily. The doctor might increase the dose as needed and tolerated. However, the dose is usually at most three mg per day.

• Children - The doctor must determine the use and dose.

Alzheimer's Disease:

• Adults - Initial, 0.5 milligrams (mg) once daily for one to seven days. The doctor might increase the dose to one mg once daily on days eight to 14 and then to 2 mg once daily on day 15. However, the dose is usually at most 3 mg per day.

• Children - The doctor must determine the use and dose.

Schizophrenia:

• Adults - Initially, one milligram (mg) once daily on days one to four. The doctor may increase the dose to 2 mg once daily on days five to seven and then to 4 mg on day eight as tolerated. However, the dose is usually at most 4 mg per day.

• Children 13 Years of Age and Older - Initially, 0.5 mg once daily on days one to four. The doctor may increase the dose to 1 mg once daily on days five to seven and then to 2 mg on day eight as tolerated. However, the dose is usually at most four mg per day.

• Children Younger Than 13 Years of Age- The doctor must determine the use and dose.

Pharmacodynamics

Brexpiprazole is rapidly absorbed after oral administration, with peak plasma concentrations reached within four hours. It undergoes hepatic metabolism primarily by cytochrome P450 (CYP) 3A4 and CYP2D6 enzymes. The elimination half-life is approximately 91 hours, allowing for once-daily dosing.

Pharmacokinetics:

• Absorption: Brexpiprazole is rapidly absorbed after oral administration, with peak plasma concentrations reached within four hours.

• Metabolism: It undergoes hepatic metabolism primarily by cytochrome P450 (CYP) enzymes, particularly CYP3A4 and CYP2D6.

• Elimination: The elimination half-life is approximately 91 hours, supporting once-daily dosing.

Mechanism of Action:

The exact mechanism of action of Brexpiprazole has yet to be completely understood. However, it is believed to involve partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors. This one-of-a-kind pharmacological profile is thought to contribute to its therapeutic effects in schizophrenia and major depressive disorder.

Adverse Effects:

Common Adverse Effects Include:

• Akathisia: Restlessness or an irresistible urge to move.

• Weight Gain: A phenomenon that has been associated with several antipsychotic medications.

• Somnolence: Drowsiness or an excessive desire to sleep.

• Fatigue: A state of weariness or diminished energy levels.

Serious Adverse Effects May Include:

• Neuroleptic Malignant Syndrome (NMS): A rare but potentially life-threatening condition characterized by hyperthermia (increased body temperature), severe muscle rigidity, altered mental status, and autonomic dysfunction.

• Tardive Dyskinesia: This results from an involuntary movement disorder that causes repetitive, purposeless movements that usually involve the face and extremities. This adverse effect can be irreversible.

• Metabolic Changes: Brexpiprazole, like other antipsychotics, may be associated with metabolic changes, including hyperglycemia and dyslipidemia.

Drug Interactions: Certain medicines must not be used together. However, in some cases, two medicines must be used together, even if an interaction might occur. The doctor might want to alter the dose or require other precautions in such cases. While taking this medicine, the healthcare professional must be informed about the medicines listed below.

Using this medicine with any of the following medicines is not advised. The doctor might decide not to treat the patient with this medication or switch to other medicines.

• Metoclopramide.

• Aprepitant.

• Atazanavir.

• Bupropion.

• Boceprevir.

• Cinacalcet.

• Clarithromycin.

• Carbamazepine.

• Conivaptan.

• Duloxetine.

• Erythromycin.

• Diltiazem.

• Dronedarone.

• Fluoxetine.

• Fosaprepitant.

• Fluconazole.

• Fosphenytoin.

• Indinavir.

• Itraconazole.

• Imatinib.

• Lopinavir.

• Nefazodone.

• Ketoconazole.

• Letermovir.

• Phenytoin.

• Posaconazole.

• Ritonavir.

• Nelfinavir.

• Paroxetine.

• Saquinavir.

• Quinidine.

• Rifampin.

• St. John's wort.

• Telaprevir.

• Verapamil.

• Telithromycin.

• Terbinafine.

• Voriconazole.

If both medicines must be prescribed together, the doctor might change the dose or frequency of one or both medicines.

Other Interactions:

Some medicines must not be used at or around the time of eating. The use of alcohol or tobacco with certain medicines may also cause interactions to occur. Using Brexpiprazole with grapefruit juice is also not recommended. If used together, the doctor might change the dose or frequency of Brexpiprazole or give special instructions about the use of food and alcohol consumption.

Use in Specific Populations:

• Allergies: Inform the doctor about any allergic reaction to Brexpiprazole or other medicines. Also, tell the health care professional about other types of allergies, such as foods, preservatives, dyes, or animals.

• Geriatric: Proper studies have not shown any geriatric-specific problems that would limit the use of Brexpiprazole in elderly patients. However, elderly patients might have age-related liver, kidney, or heart problems. These conditions might require an adjustment in the dose for patients receiving Brexpiprazole. This medicine must not be used to treat behavioral disorders in geriatric patients with dementia.

• Pediatric: Significant studies have not been performed on the consequences of Brexpiprazole for the treatment of schizophrenia in children below 13 years of age and the treatment of depression and agitation in children. Safety and efficacy have not yet been established.

• Breastfeeding: There are no adequate studies on women that prove infant risk while using this medication during breastfeeding. The potential benefits against the potential risks must be weighed before taking this medication while breastfeeding.