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Brexpiprazole (Rexulti)

FDA Approved 2015

Reviewed by the HeyPsych Medical Review Board

Board-certified psychiatrists and mental health professionals

Published November 24, 2025•Updated November 24, 2025•Reviewed November 24, 2025

Clinical summary for Brexpiprazole (Rexulti): Rexulti (brexpiprazole) is an “atypical” antipsychotic used to treat schizophrenia, help antidepressants work better in major depression, and treat agitation in people with Alzheimer’s dementia. It works on dopamine and serotonin, brain chemicals involved in mood, thinking, and behavior. It is taken once daily. Common side effects include weight gain, feeling sleepy or restless, and shakiness. Serious risks include high blood sugar and cholesterol, movement problems like tardive dyskinesia, and a higher risk of death or stroke in older adults with dementia-related psychosis. It can also raise the risk of suicidal thoughts in some younger people. Never start, stop, or change the dose on your own—always work closely with your prescriber and report new or worsening symptoms right away.

What It’s Used For

Brexpiprazole is an atypical antipsychotic that treats psychosis, mood symptoms, and agitation related to Alzheimer’s dementia.

Primary Indications

Schizophrenia in adults and adolescents ≥13 yearsAdjunctive treatment for Major Depressive Disorder (MDD) in adults who have had an incomplete response to an antidepressant aloneAgitation associated with dementia due to Alzheimer disease in adults (NOT for PRN/as-needed use)

Off-Label Uses

Investigational/under study in other mood and behavioral conditions (eg, bipolar depression, behavioral symptoms in some dementias)

What People Often Notice

Experiences vary a lot, but these are some common patterns patients describe:

Thinking and Mood

"Voices and paranoid thoughts got quieter over a few weeks."

How Fast It Works

Brexpiprazole has a long half-life and builds up gradually in the body, so effects appear slowly.

1–2 weeks

Some improvement in psychotic symptoms or mood may start.

4–6 weeks

Typical window to see full benefit for schizophrenia.

6–12 weeks

Ongoing improvement in depressive symptoms when used as an adjunctive treatment.

Once-daily dosing

Long half-life (~91 hours) allows a simple once-daily regimen.

Missed doses

Because of the long half-life, a single missed dose usually does not cause abrupt loss of effect—but never change your schedule without talking to your clinician.

Dosing Information (Clinician-Guided Only)

Adult Dosing

schizophrenia: [object Object]

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discontinuation: For chronic psychiatric conditions, a gradual taper over weeks to months is preferred when stopping (or when switching to another antipsychotic) to reduce relapse and withdrawal-like symptoms, unless a serious adverse effect requires more rapid discontinuation.

Available Formulations

  • Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg (US and Canada; brand name Rexulti).

Side Effects

Most common side effects are weight gain, metabolic changes, restlessness (akathisia), and sleepiness. Serious but less common risks include diabetes, neuroleptic malignant syndrome, stroke in older adults with dementia, and tardive dyskinesia.

Common Things People Notice

  • Weight gain and increased appetite.
  • Feeling sleepy, tired, dizzy, or less steady (fall risk).
  • Restlessness or need to move (akathisia).
  • Shakiness or tremor.
  • Headache, nausea, constipation, or dry mouth.
  • Higher blood sugar and cholesterol over time.

Common Side Effects

≥7% body weight gain in ~2–11% of patients
Weight gain— Your appetite and weight may increase over weeks to months. Regular weight checks and lifestyle changes (diet, exercise) are important.
≈1–14%
Akathisia (inner restlessness)— You may feel jittery or like you can’t sit still. Report this early—your prescriber can adjust the dose or add treatment to help.
≈3–6%
Sedation, drowsiness, fatigue— Can make you feel sleepy or mentally slower, increasing fall risk and affecting driving or work that requires focus.
Triglycerides elevated in up to ~28%; hyperglycemia reported
Metabolic changes (triglycerides, blood sugar)— Blood tests are used to watch for rising cholesterol or blood sugar. These changes may be silent but increase long-term heart and stroke risk.
Constipation, diarrhea, dyspepsia, nausea in a few percent of patients
GI symptoms— Usually mild and manageable; persistent or severe symptoms should be discussed with your clinician.

⚠️ Serious Side Effects

  • Neuroleptic Malignant Syndrome (NMS): high fever, stiff muscles, confusion, autonomic instability—medical emergency.
  • Tardive dyskinesia: involuntary movements of face, tongue, or limbs; may be irreversible, especially in older adults and with long-term use.
  • Severe hyperglycemia or new-onset diabetes: can lead to ketoacidosis, hyperosmolar coma, or death.
  • Cerebrovascular events (stroke, TIA) in older adults with dementia-related psychosis.
  • Blood dyscrasias (eg, neutropenia, agranulocytosis): increased risk of infection; may be life-threatening.
  • Seizures in susceptible individuals or at higher doses.
  • Impulse-control disorders: new or increased urges to gamble, eat, spend, or engage in risky sexual behavior.
  • Severe orthostatic hypotension and falls.

Critical Safety Information

Critical Safety Information

Increased risk of death in older adults with dementia-related psychosis; increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults.
  • →Tell your clinician right away about new or worsening depression, anxiety, agitation, or any suicidal thoughts.
  • →Report any new involuntary movements (face, tongue, limbs) immediately.
  • →Get urgent help for symptoms of stroke: weakness on one side, trouble speaking, vision changes, or facial droop.
  • →Stand up slowly from sitting or lying positions to reduce dizziness and fall risk.
  • →Keep all lab appointments to monitor blood sugar, cholesterol, and blood counts.
  • →Do not stop this medication suddenly unless your clinician tells you to; stopping abruptly can cause withdrawal-like symptoms or symptom relapse.

Important Drug Interactions

Brexpiprazole is metabolized mainly by CYP2D6 and CYP3A4 and can interact with many other medications.

With: Strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St John’s wort)

Risk: Decrease brexpiprazole levels and may reduce effectiveness.

Action: Clinicians may need to increase brexpiprazole dose or choose an alternative; do not adjust on your own.

With: Strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, certain HIV protease inhibitors)

Risk: Increase brexpiprazole levels and side effects (sedation, EPS, orthostatic hypotension).

Action: Dose reductions (often ~50%) are usually required under clinician supervision.

With: Strong CYP2D6 inhibitors (eg, fluoxetine, paroxetine, bupropion)

Risk: Increase brexpiprazole levels; higher risk of side effects including akathisia and seizures.

Action: Dose reduction is often needed; close monitoring for side effects.

With: Other antipsychotics and dopamine antagonists

Risk: Higher risk of EPS, tardive dyskinesia, NMS, and metabolic side effects.

Action: Combination usually avoided unless carefully justified by a specialist.

With: Drugs that lower seizure threshold (eg, bupropion, tramadol, many antipsychotics and antidepressants)

Risk: Increased seizure risk.

Action: Use caution and monitor; dose adjustments or alternative agents may be needed.

With: Blood pressure–lowering medications

Risk: Additive hypotension and increased fall risk.

Action: Monitor blood pressure and symptoms; adjust doses as needed.

With: Antidiabetic agents

Risk: Brexpiprazole-related hyperglycemia may blunt glucose control.

Action: Monitor blood sugar closely; antidiabetic regimens may need adjustment.

Pregnancy, Breastfeeding, and Special Groups

Brexpiprazole is often continued in pregnancy when benefits outweigh risks; decisions should be made with shared decision-making and perinatal mental health expertise.

👶Pregnancy

Brexpiprazole crosses the placenta. Overall, second-generation antipsychotics have not shown a major increase in congenital malformations as a class, but data for brexpiprazole specifically are limited. Third-trimester exposure to antipsychotics can cause neonatal EPS or withdrawal (eg, agitation, abnormal muscle tone, feeding or breathing problems). Tapering late in pregnancy is not routinely recommended because relapse risk is high; instead, use the lowest effective dose and monitor the newborn closely after birth.

🤱Breastfeeding

Brexpiprazole is present in breast milk at low levels, but case reports describe reduced milk production that improved after the drug was stopped. Antipsychotic exposure through breast milk may cause sedation, poor feeding, or motor changes in infants. Decisions about breastfeeding while on brexpiprazole should weigh maternal benefit, the importance of breastfeeding, and potential infant exposure, with close infant monitoring if breastfeeding continues.

👧Children & Adolescents (Under 18)

Approved for schizophrenia in adolescents ≥13 years; safety and efficacy for depression or Alzheimer’s agitation are not established in children. Antipsychotics in youth require careful indication, close monitoring for metabolic and movement side effects, and regular re-evaluation of the need for ongoing treatment.

👴Older Adults (65+)

Older adults are more sensitive to orthostatic hypotension, sedation, falls, metabolic changes, and cerebrovascular events. Use the lowest effective dose, titrate slowly, and reassess regularly. There is a boxed warning for increased mortality and stroke risk in older adults with dementia-related psychosis; brexpiprazole is only approved in this population for agitation associated with dementia due to Alzheimer disease.

🔬Liver Impairment

In moderate to severe hepatic impairment (Child-Pugh B or C), lower maximum doses are recommended (eg, 3 mg/day for schizophrenia; 2 mg/day for MDD adjunct and Alzheimer’s agitation).

💧Kidney Impairment

In moderate to severe renal impairment (CrCl <60 mL/min), lower maximum doses are recommended (3 mg/day schizophrenia; 2 mg/day MDD adjunct and Alzheimer’s agitation). No adjustment is needed for CrCl ≥60 mL/min.

Clinical Monitoring

  • Weight, height, BMI, and waist circumference: at baseline, 8 and 12 weeks after initiation, after dose changes, then at least quarterly.
  • Fasting glucose or HbA1c and fasting lipid panel: at baseline, 4 months after initiation, then annually (more often if abnormal).
  • Extrapyramidal symptoms and tardive dyskinesia: at every visit; use a rating scale (eg, AIMS) at least annually or every 6 months in high-risk patients.
  • CBC: as clinically indicated, especially in patients with low baseline WBC or history of drug-induced leukopenia/neutropenia.
  • Vital signs: blood pressure (including orthostatics), pulse, temperature at baseline, during titration (weekly for first 3–4 weeks), and at follow-up visits.
  • Mental status, mood, suicidality, and impulse-control behaviors: at every visit.
  • Fall risk: at baseline and regularly, especially in older adults.
  • Prolactin-related symptoms (menstrual changes, galactorrhea, sexual dysfunction): ask at visits; measure prolactin if symptomatic.
  • Adherence and functional outcomes: at every visit.

How It Works

Brexpiprazole modulates dopamine and serotonin signaling. It is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at serotonin 5-HT2A receptors. This “stabilizing” effect on dopamine can reduce psychotic symptoms while potentially causing fewer movement side effects than some older antipsychotics, and the serotonin actions may support mood and anxiety benefits.

Stopping or Switching Safely

Brexpiprazole should usually be tapered gradually when discontinued, especially after long-term use.

Key Points

  • Avoid abrupt discontinuation when possible; sudden stopping can cause symptom rebound and withdrawal-like symptoms (eg, anxiety, insomnia, agitation, flu-like symptoms, transient movement symptoms).
  • Guidelines often suggest reducing the dose slowly over weeks to months for people with chronic psychotic or mood disorders.
  • When switching antipsychotics, clinicians may use cross-titration (gradually decreasing the old drug while increasing the new one), overlap-and-taper, or other strategies tailored to the patient’s history and relapse risk.
  • Patients with multiple relapses or severe baseline illness are at higher risk for poor outcomes if antipsychotics are stopped entirely; decisions should be individualized with specialty input.

Where It Fits in Treatment

Brexpiprazole is one of several second-generation antipsychotics used for schizophrenia and as an adjunctive treatment for MDD. Clinicians may consider it when patients have had only partial response or tolerability issues with other atypicals (eg, aripiprazole-related akathisia or insomnia). For agitation in Alzheimer’s dementia, it is reserved for severe symptoms posing risk to the patient or others, after non-drug strategies are tried. Like other antipsychotics, its use should be regularly reassessed, using the lowest effective dose and monitoring for metabolic and movement side effects.

References & Further Reading

Rexulti (brexpiprazole) Prescribing Information – FDAHiemke et al. (2018) – AGNP Consensus GuidelinesAPA Schizophrenia Treatment Guidelines (2020)National Pregnancy Registry for Psychiatric Medications

Frequently Asked Questions

What is Rexulti (brexpiprazole) used for?

Rexulti is used to treat schizophrenia in adults and adolescents 13 years and older, to boost the effect of an antidepressant in adults with major depressive disorder who still have significant symptoms, and to treat agitation associated with dementia due to Alzheimer disease in adults. It is not approved as a “take it only when needed” medication.

How long does brexpiprazole take to work?

Some people notice early improvement in sleep, anxiety, or thinking within 1–2 weeks. For schizophrenia, clearer benefits often appear over 4–6 weeks. As an add-on for depression, improvements may continue over 6–12 weeks. Because it has a long half-life, it takes time to reach steady levels in your body.

What are the most common side effects of brexpiprazole?

Common side effects include weight gain, increased appetite, feeling tired or sleepy, dizziness, restlessness (akathisia), shakiness, headache, and changes in cholesterol or triglycerides. Many people tolerate it well, but ongoing monitoring is important to catch metabolic or movement side effects early.

Can brexpiprazole cause diabetes or high cholesterol?

Yes. Like other atypical antipsychotics, brexpiprazole can raise blood sugar and lipids in some patients, sometimes leading to diabetes or worsening existing diabetes. Your clinician will check fasting blood sugar or HbA1c and a fasting lipid panel at baseline, several months after starting, and then at least once a year.

What serious risks should I watch for on Rexulti?

Call your clinician or seek urgent care right away if you notice sudden weakness, trouble speaking, or facial drooping (possible stroke); high fever and stiff muscles (possible neuroleptic malignant syndrome); new or uncontrollable body movements (possible tardive dyskinesia); very high blood sugar symptoms; or new or worsening thoughts of self-harm. Older adults with dementia-related psychosis have a higher risk of death and stroke on antipsychotics.

Is brexpiprazole addictive or a controlled substance?

No. Brexpiprazole is not a controlled substance and does not cause classic physical dependence like benzodiazepines or opioids. However, stopping suddenly can still lead to withdrawal-like symptoms and relapse of the underlying condition, so any dose changes should be done slowly with your prescriber.

Can I drink alcohol while taking Rexulti?

Alcohol can increase drowsiness, dizziness, and judgment problems when combined with brexpiprazole, raising fall and accident risk. Most clinicians recommend avoiding or strictly limiting alcohol while on this medication and never driving or doing dangerous activities if you have been drinking or feel sedated.

Is brexpiprazole safe during pregnancy or breastfeeding?

Decisions about using brexpiprazole during pregnancy or breastfeeding are individualized. Untreated psychosis or severe depression also carries risks. Current data do not show a large increase in birth defects for the antipsychotic class, but late-pregnancy exposure can cause newborn withdrawal or movement symptoms. Brexpiprazole enters breast milk and may reduce milk supply in some patients. Discuss your plans for pregnancy and feeding with your prescriber so you can weigh the risks and benefits together.

What’s the difference between brexpiprazole and aripiprazole?

Both are dopamine and serotonin modulators, but brexpiprazole has lower intrinsic activity at D2 receptors and higher affinity for certain serotonin receptors (5-HT1A, 5-HT2A). Clinically, some patients find it less activating with slightly lower rates of akathisia, but both drugs share similar metabolic and movement-risk profiles. The best choice depends on your history, side effects, and response to prior treatments.

How should I stop taking Rexulti if I feel better?

Do not stop on your own. If you and your clinician decide it is time to come off Rexulti, the dose is typically reduced slowly over weeks to months. This approach lowers the risk of withdrawal-like symptoms and relapse. People with multiple past relapses or severe symptoms usually benefit from longer-term maintenance treatment.

This medication information is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider before starting, stopping, or changing any medication. Never take medication without a prescription from a licensed healthcare provider.

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