Key points
- The Rexulti label approves it for depression only as adjunctive therapy to antidepressants in adults with major depressive disorder.
- It is also approved for schizophrenia and for agitation associated with dementia due to Alzheimer's disease.
- Boxed warnings cover increased risk of death in older people with dementia-related psychosis, and suicidal thoughts and behaviors in young people.
- In adults using it for depression, the label's most common side effects are weight gain, sleepiness and akathisia.
What brexpiprazole is
Brexpiprazole is a tablet in a class called atypical antipsychotics. Rexulti is the brand name on the current FDA label, published by Otsuka. Antipsychotic is the name of the class, and having one discussed for depression does not mean a person has psychosis.
Exactly what it is approved for
The Rexulti label lists three uses:
- Adjunctive treatment to antidepressants for major depressive disorder in adults.
- Schizophrenia in adults and in young people 13 and older.
- Agitation associated with dementia due to Alzheimer's disease. The label says it is not for use on an as-needed basis for this agitation.
What the depression approval does and does not cover
The approval is specifically as an add-on. It is not approved as a stand-alone depression medicine, and it is for adults. The label's boxed warning says safety and effectiveness have not been established in children and teens with major depressive disorder.
The depression studies in the label were 6-week, placebo-controlled trials of adults who had not had an adequate response to an antidepressant during the study's lead-in phase. MedlinePlus describes the same use in plain words: depression, along with another antidepressant medicine. NIMH says atypical antipsychotics are sometimes used for depression in people who have not responded to an antidepressant alone. MedlinePlus names no off-label use for brexpiprazole, and neither do we.
If you are wondering how add-ons fit into the bigger picture, our guide to what can happen when a first antidepressant does not help walks through what prescribers commonly discuss. Our medicines list names the others in this group, without ranking them.
How it is thought to work, and what taking it can be like
The label says the way it works in depression, schizophrenia and dementia-related agitation is unknown. Its effect may come from acting as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors and blocking serotonin 5-HT2A receptors. MedlinePlus says it works by changing the activity of certain natural substances in the brain.
In the label's depression trials, the most common side effects in adults were weight gain, sleepiness and akathisia, which is a restless feeling of needing to move. MedlinePlus also lists drowsiness, tiredness and dizziness. Tell your prescriber about these so you can talk them through.
The label says brexpiprazole may impair judgment, thinking or motor skills, and advises caution with driving or machinery until you know how it affects you. MedlinePlus says not to stop taking it without talking with your doctor, even if you feel well.
Boxed warnings
The label has two boxed warnings, the FDA's strongest kind of warning.
- Older people with dementia: older adults with dementia-related psychosis treated with antipsychotic medicines are at increased risk of death. Brexpiprazole is not approved for dementia-related psychosis without agitation associated with dementia due to Alzheimer's disease. Talk to the prescriber if a family member with dementia is taking it.
- Suicidal thoughts and behaviors: antidepressants increased these risks in children, teens and young adults in short-term studies. The label calls for close monitoring of everyone on antidepressant treatment for worsening depression and for suicidal thoughts and behaviors. If you are in crisis, call or text 988, or call 911. Locascio Wellness does not provide emergency services.
Other side effects and warnings
The label also describes these risks. Some need blood tests or other checks, so plan for those.
- Neuroleptic malignant syndrome: a rare, dangerous reaction with fever, severe muscle stiffness, confusion and fast or irregular heartbeat.
- Tardive dyskinesia: movements of the face or body that a person cannot control, which can be irreversible.
- Metabolic changes: high blood sugar and diabetes, changes in blood fats, and weight gain.
- Compulsive urges: intense urges, particularly for gambling, and less often sexual urges, shopping and binge eating have been reported after the medicine came to market.
- Blood counts: low white blood cell counts, especially in people with a past history of low counts. Report fever, sore throat or other signs of infection.
- Also on the label: dizziness or fainting on standing, seizures, trouble cooling down in heat, and trouble swallowing.
- Allergy: it is contraindicated with known hypersensitivity to brexpiprazole or its components. Reactions have included rash, facial swelling, hives and anaphylaxis.
- Pregnancy: if you are pregnant, planning a pregnancy or breastfeeding, tell your prescriber.
Can brexpiprazole be managed online in Pennsylvania and New York
Video visits work for talking through mood and side effects, but blood sugar, blood fats, weight and some blood counts have to be measured outside the visit. Ask how those would be handled. Whether it is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help, using our medication inquiry form.
A licensed psychiatrist on our team treats depression by secure video for people physically located in Pennsylvania or New York during each visit. See online depression treatment and online psychiatry in Pennsylvania. Our therapists do not prescribe, and they see clients in Pennsylvania, West Virginia, Arizona, Colorado and Florida, not New York. Ask us about fees and insurance.
Common questions
Is brexpiprazole approved for depression by itself?
No. The Rexulti label approves it as adjunctive treatment to antidepressants for major depressive disorder in adults, not as a stand-alone depression medicine. It also says safety and effectiveness have not been established in children and teens with major depressive disorder. Your prescriber can explain whether an add-on is being discussed for you, and why.
Why is it approved for Alzheimer's agitation if there is a dementia warning?
The label does both. It approves treatment of agitation associated with dementia due to Alzheimer's disease, and its boxed warning says older people with dementia-related psychosis on antipsychotics face an increased risk of death. A prescriber weighs this for each person. Family members should raise questions directly with that prescriber.
Which side effects are most common with brexpiprazole?
For adults taking it as an add-on for depression, the label lists weight gain, sleepiness and akathisia, a restless need to move. MedlinePlus also mentions tiredness and dizziness. Report anything that bothers you. Call right away for fever with stiff muscles, uncontrollable movements or new thoughts of harming yourself, and call 911 in an emergency.
Can your psychiatrist prescribe brexpiprazole online?
We cannot say a visit will end in any prescription or which medicines may be right for you. Our psychiatrist sees people by secure video when they are physically in Pennsylvania or New York. Whether brexpiprazole is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help.
Sources
Published by Locascio Wellness. Published November 5, 2026. Clinically reviewed by Kenneth M. Levy, DO, Psychiatrist (Pennsylvania license OS007464L). This page is general information, not medical advice or a diagnosis.