What is brexpiprazole, and how does it work (mechanism of action)?

Brexpiprazole is an oral atypical antipsychotic used to treat schizophrenia. Other atypical antipsychotic drugs include olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify).

Atypical antipsychotics differ from typical antipsychotics because they cause a lesser degree of movement (extrapyramidal) side effects and constipation.

The exact mechanism of action of brexpiprazole is not known, but, like other anti-psychotics, it is believed that brexpiprazole affects the way the brain works by interfering with communication among the brain’s nerves. Nerves communicate with each other by making and releasing chemicals called neurotransmitters. The neurotransmitters travel to other nearby nerves where they attach to receptors on the nerves. The attachment of the neurotransmitters either stimulates or inhibits the function of the nearby nerves. Brexpiprazole blocks several of the receptors on nerves including dopamine type 2, serotonin type 2, and alpha 2 adrenergic receptors. It is believed that many psychotic illnesses are caused by abnormal communication among nerves in the brain and that by altering communication through neurotransmitters, brexpiprazole can alter the psychotic state. The FDA approved Rexulti in December, 2006.

What brand names are available for brexpiprazole?


Is brexpiprazole available as a generic drug?


Do I need a prescription for brexpiprazole?


What are the side effects of brexpiprazole?

The most common side effects include

Brexpiprazole may increase blood levels of prolactin.

Less common but serious side effects include:

  • Increased risk of stroke and death in elderly patients with dementia-related psychosis.
  • Neuroleptic malignant syndrome (NMS). NMS is a rare but serious side effect associated with the use of antipsychotics. NMS may result in death and must be treated in the hospital. Signs and symptoms of NMS may include

Extrapyramidal side effects (EPS) including:

  • Dystonia: painful spasms of the oral, throat, or neck muscles that may cause problems with speech, swallowing, and stiff neck.
  • Pseudoparkinsonism: drug induced Parkinson’s symptoms.
  • Tardive dyskinesia (TD). Tardive dyskinesia usually occurs after long-term use of antipsychotics and usually presents with abnormal uncontrollable movement problems affecting the tongue, lips, jaw, face, and extremities.
  • Metabolic changes including high blood sugar (hyperglycemia), diabetes, increase in blood cholesterol, and weight gain.
  • High blood levels of prolactin. Prolactin is a hormone that allows the production of breast milk. High levels of prolactin may cause menstrual abnormalities, leakage of milk from the breast, development of breasts in males (gynecomastia), and erection problems in men.
  • Brexpiprazole may increase risk of seizures.

What is the dosage for brexpiprazole?

  • Brexpiprazole is administered once daily by mouth with or without food.
  • The starting dose for schizophrenia is 1 mg once daily on days 1 to 4. Increase to 2 mg a day on day 5 through Day 7, then to 4 mg on Day 8 based on patient response.
  • The maximum dose is 4 mg daily.
  • The starting dose for treating depression is 0.5 mg or 1 mg once daily. The dose may be increased in weekly intervals up to a maximum dose of 3 mg daily.

Which drugs or supplements interact with brexpiprazole?

Brexpiprazole can cause low blood pressure especially when standing up from a sitting down or laying down position (orthostatic hypotension). Therefore, brexpiprazole should be used cautiously with other drugs also associated with causing orthostatic hypotension.

Brexpiprazole is metabolized or broken down by liver enzymes. Drugs that induce these enzymes will increase their activity and consequently decrease blood levels of brexpiprazole. The dose of brexpiprazole should be increased in people also taking carbamazepine (Tegretol), rifampin (Rifadin), St. John’s Wort, and other drugs that may decrease its blood levels.

Drugs that block the action of enzymes that breakdown brexpiprazole will increase blood levels and side effects of brexpiprazole. The dose of brexpiprazole should be reduced in people who are also taking itraconazole (Sporanox), clarithromycin (Biaxin), ketoconazole, paroxetine (Paxil), fluoxetine (Prozac), quinidine, and other drugs that may increase its blood levels. The dose of brexpiprazole also should be reduced in people whose liver enzymes are less active than the general population.

Is brexpiprazole safe to take if I’m pregnant or breastfeeding?

Unborn babies exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and withdrawal symptoms after birth. Symptoms reported included agitation, hypertonia, hypotonia, tremor, somnolence, depressed breathing, and feeding disorder. Currently there is no data on the use of brexpiprazole during pregnancy. Brexpiprazole should only be used during pregnancy if the potential benefit to the mother outweighs the potential for side effects in the unborn baby.

A pregnancy exposure registry has been established to monitor the use of atypical antipsychotics, including brexpiprazole, during pregnancy. All pregnant women treated with atypical antipsychotics are advised to enroll in this pregnancy registry and report any side effects.

Brexpiprazole is known to enter human milk but its effects on the breastfeeding infant or milk production is not yet known.

What else should I know about brexpiprazole?

What preparations of brexpiprazole are available?

Tablets: 0.25, 0.5, 1, 2, 3, and 4 mg

How should I keep brexpiprazole stored?

Brexpiprazole should be stored at room temperature, between 15 C and 30 C (59 F and 86 F).

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Medically Reviewed on 3/14/2019


Medically reviewed by John P. Cunha, DO, FACOEP; Board Certified Emergency Medicine


FDA Prescribing Information