How does Rexulti work?

Rexulti's exact mechanism of action (the way it works) in MDD and schizophrenia is not fully understood. However, the drug has activity at specific serotonin-5-HT1A and dopamine D2 receptors. It also blocks activity at certain other serotonin receptors. This synergistic action is thought to help regulate the imbalance of dopamine and serotonin in the brain.

What side effects can I expect while taking Rexulti?

The most common side effects of Rexulti are elevated blood sugars, elevated cholesterol, weight gain, restlessness (akathisia), and headaches.

How much weight do people gain on Rexulti?

In clinical trials of Rexulti for depression and schizophrenia, the average weight gain after being on the medication for one year was 2 to 3 kilograms (4 to 5 pounds). Twenty to 30% of people experienced a greater than 7% increase in body weight.

Rexulti (Brexpiprazole) Oral: Uses, Side Effects, Dosages

Warning:

There is an increased risk of death when antipsychotic medications are used in older adults (65 and above) with dementia-related psychosis. Rexulti is not approved for the treatment of dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behavior in people 24 years and younger in short-term studies. Rexulti is not approved for the treatment of major depressive disorder in children. In young people, monitor closely for the development of suicidal thoughts and behavior.

…

What Is Rexulti?

Rexulti (brexpiprazole) is an atypical antipsychotic, also known as a second-generation antipsychotic, used to treat psychiatric conditions, such as major depressive disorder and schizophrenia.

Rexulti is thought to work by mimicking the activity of serotonin and dopamine at specific serotonin 5-HT1A receptors and dopamine D2 receptors while blocking activity at other serotonin receptors. This helps balance these chemicals in the brain. Serotonin and dopamine are neurotransmitters in the brain that plays a role in mood and other mental and emotional functions.

Rexulti is available by prescription as an oral tablet.

Drug Facts

Generic Name: Brexpiprazole

Brand Name(s): Rexulti

Drug Availability: Prescription

Administration Route: Oral

Therapeutic Classification: Atypical antipsychotic

Available Generically: No

Controlled Substance: N/A

Active Ingredient: Brexpiprazole

Dosage Form(s): Tablet

What Is Rexulti Used For?

The Food and Drug Administration (FDA) approved Rexulti:

As an adjunctive (add-on) treatment for major depressive disorder (MDD) in adults
To treat schizophrenia in adults and children 13 years and older.

Rexulti may be used for MDD in people who aren't responding well to other antidepressant therapy. It is prescribed along with another antidepressant, not by itself. In schizophrenia, the goal of treatment is to manage and reduce the severity of symptoms. Symptoms associated with schizophrenia include:

Hallucinations
Delusions
Difficulty thinking or speaking
Lack of motivation

How to Take Rexulti

Take Rexulti as prescribed, usually once daily, with or without food. For both MDD and schizophrenia, your healthcare provider may slowly increase the dose based on response and tolerability.

Storage

Store at room temperature (between 68 F and 77 F) and protect from light and moisture. Do not store it in the bathroom.

How Long Does Rexulti Take to Work?

Clinical trials looked at Rexulti for both schizophrenia and as an adjunct to antidepressant therapy in MDD. According to the results, people taking Rexulti began seeing symptom improvement after one week compared with the placebo group, with this improvement increasing through six weeks.

What Are the Side Effects of Rexulti?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 1-800-FDA-1088.

Common Side Effects

Common side effects of Rexulti include:

Elevated blood sugar levels
Elevated triglyceride levels
Weight gain
Akathisia (restlessness)
Extrapyramidal movements (involuntary movements)
Headache

Severe Side Effects

Contact your healthcare provider immediately if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects can include the following:

Stroke or transient ischemic attack (TIA), also called a mini-stroke: Symptoms may include facial weakness, arm or leg weakness, and slurred speech.
Ketoacidosis (a severe complication of diabetes): Signs can include increased thirst, frequent urination, fast and deep breathing, and fruity-smelling breath.
Agranulocytosis (a rare, drug-induced blood disorder): Agranulocytosis is characterized by severely reduced white blood cell counts in the circulating blood.
Seizures
Neuroleptic malignant syndrome: Common symptoms include muscular rigidity and extremely high body temperature (102 F to 104 F), irregular pulse, increased breathing rate, and accelerated heartbeat.
Increased suicidal thoughts and behaviors

Rexulti has a boxed warning about the heightened risk of suicidal thinking and behavior in people 24 years and younger. Be aware of new or worsening depression or suicidal thoughts. Immediately contact your healthcare provider if you start to experience severe side effects. While on treatment, have a family member or loved one keep an eye out for abnormal changes in your behavior, especially if you are just starting the medication or switching to a new dose.

Long-Term Side Effects

With long-term use, some people may experience metabolic changes including elevated blood sugar levels, diabetes, elevated cholesterol levels, and weight gain. The average amount of weight gain observed in clinical trials at one year was 2 to 3 kilograms (about 4 to 5 pounds).

Tardive dyskinesia is characterized by involuntary, dyskinetic body movements associated with antipsychotic drugs including Rexulti. It is recommended to use the lowest dose for the shortest possible duration and periodically reassess the need for continued therapy. Talk to your healthcare provider if you notice these abnormal movements.

Report Side Effects

Rexulti may cause other side effects. Call your healthcare provider if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your healthcare provider may send a report to the FDA's MedWatch Adverse Event Reporting Program or by phone (800-332-1088).

(800) 332-1088

Dosage: How Much Rexulti Should I Take?

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets):
- For depression:
  - Adults—At first, 0.5 or 1 milligram (mg) once a day. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 3 mg per day.
  - Children—Use and dose must be determined by your doctor.
- For schizophrenia
  - Adults—At first, 1 milligram (mg) once a day on Days 1 to 4. Your doctor may increase your dose to 2 mg on Days 5 to 7, and then to 4 mg on Day 8 as tolerated. However, the dose is usually not more than 4 mg per day.
  - Children—Use and dose must be determined by your doctor.

Modifications

Due to the possible effects of this medication, there may be changes to how it is taken. Certain factors may affect your dosage of this medication.

Pregnancy

Taking Rexulti during pregnancy has not been established as safe. Newborns exposed to antipsychotic drugs like Rexulti in utero (before birth) in the third trimester are at risk for extrapyramidal and withdrawal symptoms, such as:

Agitation
Increased or decrease muscle tone
Tremor
Somnolence
Respiratory distress
Feeding disorders

Severity varies, with some newborns recovering spontaneously within hours while others require prolonged hospitalization. The decision to take Rexulti during pregnancy should be carefully weighed between the benefits of maintaining stable mental health and the potential risks to the newborn.

Breastfeeding

It is not known if Rexulti is excreted in human breast milk. One published case report suggests that Rexulti may decrease milk production. Lactating individuals needing treatment with an atypical antipsychotic may consider alternatives such as Zyprexa (olanzapine), Seroquel (quetiapine), or Risperdal (risperidone). These drugs have more published data on use in lactation.

Age

The safety and effectiveness of Rexulti for treating schizophrenia in people 13 years and older are supported by clinical trials in this population. However, the safety and efficacy of treating MDD in children have not been established.

Clinical trials of Rexulti did not include any individuals 65 and older to determine if there is a difference in safety or efficacy compared with younger people. Antipsychotic drugs increase the risk of death in older adults (65 and older) with dementia-related psychosis and should not be used in this population.

Missed Dose

If you miss a dose of Rexulti, take it as soon as you remember. If it is almost time for your next dose, wait until that time and take your regular dose. Do not double up on the medication to make up for a missed dose.

Overdose: What Happens If I Take Too Much Rexulti?

Overdose symptoms may include akathisia and drowsiness. Overdoses of Rexulti should be treated symptomatically, including airway management, oxygenation, and symptom management.

What Happens If I Overdose On Rexulti?

If you think you or someone else may have overdosed on Rexulti, call a healthcare provider or the Poison Control Center. (800-222-1222).
If someone collapses or isn’t breathing after taking Rexulti, call 911.

911

Precautions

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to make sure this medicine is working properly. Blood and urine tests may be needed to check for any unwanted effects.

For some patients, this medicine can increase thoughts of suicide. Tell your doctor right away if you start to feel more depressed and have thoughts about hurting yourself. Report any unusual thoughts or behaviors that trouble you, especially if they are new or are getting worse quickly. Make sure the doctor knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive illness) or has tried to commit suicide.

Check with your doctor right away if you have any of the following symptoms while using this medicine: convulsions (seizures), difficulty with breathing, a fast heartbeat, a high fever, high or low blood pressure, increased sweating, loss of bladder control, severe muscle stiffness, unusually pale skin, or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).

This medicine may cause tardive dyskinesia (a movement disorder) especially in elderly women. Check with your doctor right away if you have any of the following symptoms while taking this medicine: lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.

This medicine may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or increased urination. If you have diabetes, you may notice a change in the results of your urine or blood sugar tests. If you have any questions, check with your doctor.

This medicine may increase your weight. Your doctor may need to check your weight on a regular basis while you are using this medicine.

Some people who have used this medicine had unusual changes in their behavior. Talk with your doctor right away if you start having unusual urges, such as gambling urges, binge or compulsive eating, compulsive shopping, or sexual urges while using this medicine.

This medicine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.

Dizziness, lightheadedness, or fainting may occur, especially when you get up from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.

This medicine may make it more difficult for your body to cool down. It might also reduce how much you sweat. Your body could get too hot if you do not sweat enough. If your body gets too hot, you might feel dizzy, weak, tired, or confused. You might have an upset stomach or vomit. Call your doctor if drinking cool water and moving away from the heat does not cool you down.

This medicine may cause drowsiness, dizziness, trouble with thinking, or trouble with controlling movements, which may lead to falls, fractures, or other injuries. Do not drive or do anything else that could be dangerous until you know how this medicine affects you. Stand or sit up slowly if you feel lightheaded or dizzy.

Do not change the dose or stop using this medicine without checking first with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines) and herbal (eg, St. John's wort) or vitamin supplements.

What Are Reasons I Shouldn’t Take Rexulti?

Rexulti should not be used in:

People with a hypersensitivity to brexpiprazole or any of its components.
Older adults with dementia, as this can increase the risk of death during treatment. Older adults with dementia are also more likely to have a stroke or ministroke while taking antipsychotics.
Children younger than 12 for depression due to the increased risk of suicidal thinking or behavior.

What Other Medications Interact With Rexulti?

Rexulti interacts with the following types of drugs:

Certain drugs called strong cytochrome P450 3A4 (CYP3A4) inhibitors and strong cytochrome P450 2D6 (CYP2D6) inhibitors: Taking one or more drugs that strongly inhibit the enzymes CYP3A4 or CYP2D6 increases the exposure to blood levels of brexpiprazole. If this combination is used, reduce the dose of Rexulti.
Strong CYP3A4 inducers: Using a strong inducer of the CYP3A4 enzyme reduces exposure to blood levels of brexpiprazole. To manage this interaction, you'll need to increase the dose of Rexulti.

Ask your healthcare provider if you are unsure whether any of the medications you take fall under the above categories.

Examples of strong CYP3A4 or CYP2D6 inhibitors include:

Paxil (paroxetine)
Prozac (fluoxetine)
Aplenzin, Wellbutrin XL (bupropion)
Quinidine
Norvir (ritonavir)
Sporanox (itraconazole)
Ketocaonzole

Examples of strong CYP3A4 inducers include:

Phenobarbital
Dilantin (phenytoin)
Rifampin
St John's wort

Ask your healthcare provider or pharmacist for a complete list of drug interactions that can occur with Rexulti. Tell your healthcare provider about all prescription drugs, over-the-counter (OTC) drugs, vitamins, and herbal supplements you take.

What Medications Are Similar?

Rexulti is an atypical antipsychotic, also known as a second-generation antipsychotic. Other atypical antipsychotics include:

Abilify (aripiprazole)
Saphris (asenapine)
Vraylar (cariprazine)
Clozaril (clozapine)
Fanapt (iloperidone)
Caplyta (lumateperone)
Latuda (lurasidone)
Zyprexa (olanzapine)
Invega (paliperidone)
Nuplazid (pimavanserin)
Seroquel (quetiapine)
Risperdal (risperidone)
Geodon (ziprasidone)

People generally only take one oral atypical antipsychotic at a time. However, oral formulations may be prescribed in addition to injectable antipsychotics.

Frequently Asked Questions

How does Rexulti work?

Rexulti's exact mechanism of action (the way it works) in MDD and schizophrenia is not fully understood. However, the drug has activity at specific serotonin-5-HT1A and dopamine D2 receptors. It also blocks activity at certain other serotonin receptors. This synergistic action is thought to help regulate the imbalance of dopamine and serotonin in the brain.
What side effects can I expect while taking Rexulti?

The most common side effects of Rexulti are elevated blood sugars, elevated cholesterol, weight gain, restlessness (akathisia), and headaches.
How much weight do people gain on Rexulti?

In clinical trials of Rexulti for depression and schizophrenia, the average weight gain after being on the medication for one year was 2 to 3 kilograms (4 to 5 pounds). Twenty to 30% of people experienced a greater than 7% increase in body weight.

How Can I Stay Healthy While Taking Rexulti?

Rexulti may increase suicidal thoughts or behaviors. Pay close attention to any sudden changes in mood, behaviors, thoughts, or feelings, especially within the first few months of treatment or when starting or changing a dose. Seek medical attention from a healthcare provider if you develop suicidal thoughts or actions or any sudden worsening of mental health.

Other symptoms that warrant an immediate evaluation by a healthcare provider include:

Uncontrolled body movements
High fevers
Increased sweating
Changes in breathing or heart rate
Extreme thirst or hunger
Needing to urinate more than usual
Falls
Seizures

Keep all medical appointments with your healthcare provider. This medication requires regular monitoring of metabolic parameters such as weight, blood sugar, and cholesterol levels. Maintain a healthy lifestyle, including a healthy diet and regular exercise.

When to Seek Emergency Help

If you think you may be in a position to harm yourself or someone else, call 911 or your local emergency number ASAP. There are also several treatment resources and support groups that can be sought through the Substance Abuse and Mental Health Service Administration (SAMHSA) National Hotline at 1-800-662-HELP (4357).

If you are having suicidal thoughts, dial 988 to contact the 988 Suicide & Crisis Lifeline and connect with a trained counselor. If you or a loved one are in immediate danger, call 911.

Medical Disclaimer

Verywell Health's drug information is meant for educational purposes only and is not intended to replace medical advice, diagnosis, or treatment from a healthcare provider. Consult your healthcare provider before taking any new medication(s). IBM Watson Micromedex provides some of the drug content, as indicated on the page.

9 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Food and Drug Administration. Rexulti prescribing information.
Eaves S, Rey JA. Brexpiprazole (Rexulti): a new monotherapy for schizophrenia and adjunctive therapy for major depressive disorder. P T. 2016;41(7):418-422.
National Alliance on Mental Illness. Schizophrenia.
Centers for Disease Control and Prevention. Stroke signs and symptoms.
Centers for Disease Control and Prevention. Diabetic ketoacidosis.
National Organization of Rare Diseases. Agranulocytosis, acquired.
National Organization for Rare Disorders. Neuroleptic malignant syndrome.
Food and Drug Administration. FDA drug safety communication: antipsychotic drug labels updated on use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns.
Brexpiprazole. In: Drugs and Lactation Database (LactMed). National Library of Medicine

By Carrie Yuan, PharmD
Carrie Yuan PharmD is a clinical pharmacist with expertise in chronic disease medication management for conditions encountered in primary care.

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Rexulti (Brexpiprazole) - Oral