Rexulti (Brexpiprazole): What It Treats, Its Side Effects, and How It Compares With Abilify

An antipsychotic prescribed for depression confuses almost everyone. The confusion is reasonable — and the answer is more useful than “it treats chemical imbalance.” Here is what the FDA label supports, and what it does not.

What to know

• Rexulti has three FDA-approved uses, and they are not interchangeable: an add-on to an antidepressant for depression in adults, schizophrenia in adults and young people 13 and older, and agitation associated with dementia due to Alzheimer disease.[1,2]
• It is an antipsychotic by drug class, not an antidepressant. For depression it is added to an antidepressant, never used alone.[1]
• The benefits are real but modest on average. In the depression trials, the improvement over placebo was 3.2 points on a 60-point scale. Some people improve far more, some not at all.[1]
• The boxed warning still applies. Antipsychotics raise the risk of death in older adults with dementia-related psychosis, and approval for Alzheimer-related agitation does not cancel that.[1]
• For Alzheimer agitation, Rexulti is no longer the only option. It was the first, approved in May 2023. On April 30, 2026, the FDA approved a second treatment — Auvelity, a combination of dextromethorphan and bupropion, which is not an antipsychotic.[3,4,5]
• It is not approved for bipolar disorder, anxiety, insomnia, autism-related irritability, or PTSD, no matter how often those uses come up in conversation.[1]

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The short answer

Rexulti is the brand name for brexpiprazole. It is a second-generation, or atypical, antipsychotic. The FDA label, last revised in April 2026, approves it for exactly three things:[1,2]

1. As an add-on to an antidepressant for major depressive disorder in adults
2. Schizophrenia in adults and young people age 13 and older
3. Agitation associated with dementia due to Alzheimer disease

That last use comes with a specific limit written into the label: Rexulti is not an as-needed medicine for agitation. It is not meant to be given only when a bad afternoon arrives.[1]

Is Rexulti an antidepressant or an antipsychotic?

It is an antipsychotic by drug class. For adult depression, it is used as an augmentation medicine — a second medicine added when an antidepressant has helped, but not enough.

Being prescribed an antipsychotic does not mean anyone thinks you have psychosis. A drug class describes a medicine’s chemistry and history. It does not describe the person taking it. Several medicines in this class are used for depression, and that use is ordinary psychiatric practice.

How Rexulti works

Brain cells talk to each other using chemical messengers, including dopamine and serotonin. Rexulti attaches to several of the receptors that receive those messages.

At dopamine D2 and serotonin 5-HT1A receptors, Rexulti is a partial agonist. It turns the receptor on, but not as strongly as the brain’s own messenger would. At serotonin 5-HT2A receptors, it mostly blocks.[1]

Think of a dimmer switch. It can add light to a dark room, and it can also keep a bright room from getting brighter. That is roughly what a partial agonist does, and it is why one receptor action can have different effects in different brain circuits.

The comparison has limits. A brain is not one room. Rexulti is not a smart switch that measures what each circuit needs. What it does depends on the activity already there, the dose, how long someone has taken it, and its effects at other receptors.

Here is the honest part, and the label says it plainly: exactly how brexpiprazole improves depression, schizophrenia, or agitation is not known.[1] Anyone who tells you it “rebalances your brain chemicals” is describing a slogan, not the science.

A short FDA timeline

A note on the 2023 date: the FDA’s approval action is recorded as May 10, 2023, and the agency announced it publicly on May 11.[3,4] Both dates describe one approval.

How well does it work for depression?

The two main trials enrolled adults whose depression had not improved enough after one to three previous antidepressant treatments — and who then went through an additional eight weeks on an antidepressant without substantial improvement. Only then did they continue that antidepressant and add either Rexulti or a placebo for six weeks.[1,7,8]

Depression was measured with the Montgomery-Åsberg Depression Rating Scale, or MADRS. It runs from 0 to 60. Lower is better. The average person entered these trials at about 27.[1]

Here is what happened at week 6:[1,7,8]

Three things are worth sitting with.

The placebo groups improved too — by 5 to 6 points. That is most of the improvement seen in the Rexulti groups. It reflects time, attention, continued antidepressant treatment, and the natural course of a depressive episode.

The extra benefit is a group average. Some people in these trials improved a great deal. Others did not improve at all. A 3.2-point average does not predict any one person’s experience.

The lowest dose did not work in the study that tested it, which is a real finding rather than a rounding error.

A 2023 Cochrane review pooled nine studies and 3,424 participants. It found that adding brexpiprazole to an antidepressant did improve the chance of response and of remission compared with placebo, and rated the certainty of that efficacy evidence as high. It also found that akathisia and weight gain were about three times more likely than with placebo, rated as moderate certainty. What the reviewers said was missing: trials comparing brexpiprazole head-to-head with other antidepressant strategies, trials of adding it after only one failed antidepressant, and evidence about long-term benefit.[9]

That last gap matters. We do not have good controlled evidence about how well Rexulti prevents future depressive episodes when used as an add-on over years.

How well does it work for schizophrenia?

In two six-week trials in adults, symptoms were measured with the Positive and Negative Syndrome Scale, or PANSS, which runs from 30 to 210. Lower is better.[1,10,11]

Doses that worked improved scores by about 6.5 to 8.7 points more than placebo. But not every dose worked in every study. In the second trial, the 2 mg group did not separate from placebo at all.[1]

A separate study took adults who had already stabilized on Rexulti for at least 12 weeks and randomly either continued it or switched them to placebo. Those who stayed on Rexulti went longer before relapsing, and the study was stopped early once that was clear.[1,12] That design supports staying on a medicine that is already working. It does not tell you how a new patient will respond.

For ages 13 to 17, a six-week trial found a 5.3-point PANSS advantage over placebo with flexible doses of 2 to 4 mg.[1,13] That supports short-term benefit. Long-term treatment during adolescence still calls for close attention to growth, weight, metabolism, movement effects, and prolactin.

One piece of reassurance on the pediatric side. In May 2025, FDA pharmacovigilance staff reviewed every serious U.S. adverse-event report involving brexpiprazole in patients under 18 from July 2015 through May 2025. They found 37 reports, identified no new safety signals, no increase in the severity of known side effects, and no deaths directly associated with the medicine in that age group.[6] That is not the same as proving long-term safety, but it is a real check that came back clean.

What the Alzheimer agitation approval means

This is the use that generates the most worry, and it deserves the most care.

What “agitation” meant in these trials. Not every difficult moment. The trials required a diagnosis of probable Alzheimer disease, a Mini-Mental State Examination score between 5 and 22, and agitation severe enough that a clinician judged medication was warranted — pacing, restlessness, repeated demands, screaming, cursing, throwing things, hitting, kicking, pushing.[1,3]

Non-drug approaches came first, and that was a requirement. To enter the main trial, a person had to have already been evaluated for reversible causes such as pain, infection, and medication effects, and to have already tried non-drug approaches such as redirection, group activities, or music therapy. New non-drug interventions were not even permitted during the study.[14] So these trials did not test medicine versus good care. They tested medicine in people for whom good care had not been enough.

That is the right order in real life, too. Before reaching for a medicine, it is worth looking hard at pain, constipation, infection, delirium, poor sleep, a new prescription, hunger, fear, noise, boredom, or a need someone cannot put into words.

What the trials found. Two 12-week studies measured agitation with the Cohen-Mansfield Agitation Inventory, a 29-item caregiver-informed scale running from 29 to 203.[1]

The second study reported an effect size of 0.35, which statisticians would call small to moderate.[5,15]

Read those placebo columns again. People in the placebo groups improved by about 17 points. The medicine’s added benefit was 4 to 5 points on top of that. The result was real and statistically significant. It is also modest, and a number on a rating scale does not tell a family what they will actually notice at home.

The boxed warning does not go away. Antipsychotics increase the risk of death in older adults with dementia-related psychosis. Rexulti is approved only for agitation associated with dementia due to Alzheimer disease — not for dementia-related psychosis without that qualifying agitation.[1]

And there is now a second approved option. For nearly three years Rexulti was the only medicine FDA had approved for this problem. That changed on April 30, 2026, when the FDA approved Auvelity — a combination of dextromethorphan and bupropion — for agitation associated with dementia due to Alzheimer disease. It is the first approved treatment for this use that is not an antipsychotic, which means it does not carry the same class mortality warning. Like Rexulti, it is not approved for as-needed use.[16,17]

Two approved options is not the same as one being better. There is no trial comparing them. But a family weighing this decision now has a genuine choice to raise with the prescriber, and that is worth knowing.

How long does Rexulti take to work?

There is no single answer, and the honest version has several parts.

• Blood levels peak about four hours after a dose.[1]
• Steady levels take about 10 to 12 days.[1]
• Side effects such as sleepiness, dizziness, or restlessness can show up before any benefit does.
• The depression and schizophrenia trials measured their main result at week 6.
• The Alzheimer agitation trials measured theirs at week 12.

Rexulti has a long half-life — about 91 hours, or nearly four days.[1] It leaves the body slowly. That smooths out blood levels, and it also means a dose change or a side effect can take a week or more to show its full shape, or to fade.

A difference measured in a trial at week 6 is not a promise about any individual by week 6.

Common side effects

Which numbers matter depends on why the medicine is being used. These are all from the label’s pooled trial data.[1]

In the depression trials, akathisia and restlessness both became more common as the dose went up.[1]

Other reported effects include headache, nausea, constipation, fatigue, tremor, increased appetite, and dizziness.

What akathisia actually feels like

Akathisia is an inner restlessness — a physical need to move that comes from the medicine, not from mood. People describe pacing, rocking, bouncing a leg, or being unable to sit through a meal or a television show.

It is often mistaken for anxiety, for the illness getting worse, or for agitation in someone who cannot describe what they feel. That mistake can lead to the wrong response: raising the dose of the medicine causing it.

If new restlessness appears, tell the prescriber promptly. Severe akathisia is genuinely distressing and needs to be assessed, not endured.

Weight, blood sugar, and cholesterol

Rexulti can cause weight gain and other metabolic changes, and the label specifically directs monitoring of weight, blood sugar, and lipids.[1]

In the six-week depression studies, average weight went up about 1.3 to 1.6 kg (roughly 3 to 3.5 pounds) with Rexulti, versus 0.3 kg with placebo. In longer open-label depression studies, the average gain was about 3.1 kg at one year, and 30% of people gained at least 7% of their starting weight.[1]

In adult schizophrenia trials, average gain was 1.0 to 1.2 kg versus 0.2 kg with placebo, and 10% to 11% gained at least 7% of their body weight versus 4% on placebo.[1]

In teenagers, 8.2% gained at least 7% of their body weight over six weeks, versus 4.9% on placebo. In growing adolescents, weight has to be judged against expected growth, not against a flat line.[1]

Open-label results do not prove the medicine caused every pound. They do explain why weight, glucose or A1c, and lipids belong on the follow-up list rather than in the “we’ll see” pile.

Serious risks and urgent warning signs

Call the prescriber promptly for new abnormal movements, severe restlessness, repeated falls, faintness, trouble swallowing, heavy sedation, or new compulsive gambling, shopping, sexual behavior, or binge eating. That last group is a recognized label warning, and people rarely bring it up unprompted — it is worth asking about directly.[1]

Seek urgent medical help for:

• high fever with stiff muscles, confusion, sweating, or an unstable pulse or blood pressure — this can signal neuroleptic malignant syndrome, which is rare and life-threatening;
• a severe allergic reaction, including facial swelling or trouble breathing;
• severe or quickly worsening abnormal movements;
• fainting with injury, or a seizure;
• immediate danger from thoughts of suicide.

Other serious risks named on the label include tardive dyskinesia, low white blood cell counts, low blood pressure on standing, falls, seizures, trouble regulating body temperature, swallowing problems, and impaired driving or machine operation.[1]

The label also carries the antidepressant class warning about suicidal thoughts and behaviors in children, adolescents, and young adults — which applies when Rexulti is added to an antidepressant. Anyone starting or changing this combination should be watched closely for clinical worsening in the early weeks.[1]

What should be monitored?

Before and during treatment, these are fair things to ask your clinician about:

• the exact symptom Rexulti is meant to change, and how you will both know whether it worked;
• weight and BMI, blood pressure, glucose or A1c, and lipids;
• restlessness, stiffness, tremor, and any abnormal movements, checked at visits;
• sleepiness, falls, driving, and any alcohol, cannabis, or sedating medicines;
• every prescription, over-the-counter product, and supplement you take;
• kidney or liver problems;
• pregnancy, pregnancy planning, and breastfeeding;
• a specific date to reassess whether the medicine is still earning its place.

For Alzheimer-related agitation, a caregiver’s written notes are worth more than memory. A short record of what happened, how often, what came before it, and whether anyone was at risk of harm is far more useful than “a rough week.”

No single monitoring schedule fits everyone. Timing should follow current guidelines and the individual’s own risks.[1,18]

Drug interactions and special situations

Rexulti is broken down mainly by two liver enzymes, CYP2D6 and CYP3A4. That produces some specific, concrete instructions on the label:[1]

• Strong CYP3A4 inhibitors, or strong CYP2D6 inhibitors: half the usual dose.
• Both together, or a CYP2D6 poor metabolizer taking a CYP3A4 inhibitor: a quarter of the usual dose.
• Strong CYP3A4 inducers: double the dose over one to two weeks.
• People who are CYP2D6 poor metabolizers by genetics: half the usual dose.

There is one exception worth knowing about, because it surprises people. In the depression trials, doses were not adjusted for strong CYP2D6 inhibitors such as paroxetine and fluoxetine. So for the depression use, that adjustment is already built into the standard dosing.[1]

Kidneys and liver. With a creatinine clearance below 60 mL/min, or moderate to severe liver impairment, the maximum dose is lowered.[1]

Older adults may be more sensitive to dizziness, low blood pressure, sedation, and falls.

Sedating substances — alcohol, opioids, benzodiazepines, cannabis, sleep medicines — can add to sleepiness and impairment.

Pregnancy and breastfeeding. Exposure in the third trimester can cause movement or withdrawal symptoms in a newborn. Breastfeeding data are limited. These are reasons for a careful conversation, not reasons to stop a medicine abruptly on your own. There is a National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 that collects exactly this kind of information.[1,19]

Rexulti versus Abilify

These two are related. They are not interchangeable.

Laboratory studies show brexpiprazole turns the D2 receptor on less strongly than aripiprazole does, and has a somewhat different profile at serotonin and adrenergic receptors.[20] That is a genuine chemical difference, and it is why some clinicians expect Rexulti to feel less activating.

But expectation is not evidence. Network analyses comparing the two in acute schizophrenia found no dependable overall winner, and a similar analysis in Japanese patients with depression found no significant difference in outcomes between them.[21,22] Direct head-to-head trials are essentially absent.

So Rexulti is not simply “a new and improved Abilify.” The better choice depends on the diagnosis, what someone has already responded to, which side effects they can least afford, whether a long-acting injection would help, drug interactions, cost, and what the person actually wants.

How Rexulti compares with other options

For adding to an antidepressant, the FDA-approved partners include aripiprazole, cariprazine, quetiapine XR, the olanzapine-fluoxetine combination, and — since November 2025 — lumateperone.[23] Broad patterns: quetiapine tends to bring more sedation and metabolic burden; aripiprazole and cariprazine tend to raise more concern about akathisia; the olanzapine-fluoxetine combination carries the heaviest weight and metabolic load.

A 2026 network meta-analysis in JAMA Psychiatry ranked these options for response and for how many people stopped taking them.[24] Rankings like that are useful for a conversation. They should not pick a drug by themselves, because they compare studies rather than patients, most of the trials were short, and populations differed.

For schizophrenia, lurasidone and the dopamine partial agonists generally carry less metabolic burden than olanzapine; risperidone raises prolactin more; quetiapine sedates more. For many people, whether a long-acting injection is available matters more than a few points of difference in a six-week trial score.

No antipsychotic is the best one for everyone. That is not a hedge — it is the actual state of the evidence.

What Rexulti is not approved to treat

Rexulti is not FDA approved for:

• bipolar disorder — two phase 3 trials in acute mania did not separate from placebo on their main measure at week 3;[25]
• irritability associated with autism — a trial in 119 children and teens failed to establish it works, and that failure is recorded in the label;[1]
• PTSD;
• generalized anxiety disorder;
• insomnia;
• dementia-related psychosis without qualifying agitation due to Alzheimer disease;[1]
• as-needed treatment of agitation.[1]

Prescribing outside an approved use — “off-label” — can be entirely reasonable medicine. It should just be named out loud, with a specific reason, so that everyone knows the evidence is thinner.

What happened with PTSD

This one is worth telling properly, because it is often reported wrong.

The proposal was to start brexpiprazole together with sertraline in adults with PTSD. The FDA ran two large phase 3 trials against sertraline plus placebo. In the agency’s own words at the advisory meeting: “One of those studies was robustly positive; the other was clearly and convincingly negative.” Despite extensive analysis, FDA could not explain the contradiction. An earlier phase 2 study was designed to generate hypotheses, and its analyses were chosen afterward, so it could not supply the missing statistical proof.[26]

On July 18, 2025, the Psychopharmacologic Drugs Advisory Committee was asked whether efficacy had been established for brexpiprazole started together with sertraline for PTSD. The vote was 1 yes, 10 no, no abstentions.[26]

An advisory committee vote is a recommendation, not a final FDA decision. The clearest fact available today is simpler: the April 2026 Rexulti label does not include PTSD.[1]

What about generics and cost?

The FDA has approved a dozen generic versions of brexpiprazole, the first back in August 2022.[4] But approval and availability are different things. As of this review, only one generic manufacturer had an active label listing in the national drug database.[27]

There is also a labeling quirk worth understanding if you ever compare a generic’s paperwork with the brand’s. Because Otsuka holds marketing exclusivity for the pediatric information, generic labels are legally permitted to leave it out. The Ajanta generic label, for example, lists only two indications — adult depression add-on and adult schizophrenia — and says so directly.[27] That is a legal difference in paperwork, not a different medicine.

Cost, coverage, and what is actually on the shelf change constantly. Check them at the time of prescribing.

What we still do not know

• How well it prevents future depressive episodes when used long term as an add-on
• Long-term outcomes for adolescents, including growth and metabolic effects
• How it performs in frail, medically complex older adults, who were largely not studied
• How it works in dementia that is not Alzheimer disease, or in mixed dementias
• Whether rating-scale improvements translate into better function, quality of life, or reduced caregiver strain
• How its mortality and stroke risks in dementia compare with those of other antipsychotics
• How long to continue it, and how best to stop it
• How it compares directly with common alternatives, since almost no head-to-head trials exist

The pivotal trials were funded by the manufacturers. Most lasted six or twelve weeks. Most excluded medically complicated patients. The dementia trials enrolled populations that were about 95% White, which limits what can be said about everyone else.[1]

None of that erases positive results. It narrows what those results can prove.

Bottom line

Rexulti is one medicine doing three different jobs. It can be added to an antidepressant for adult depression, treat schizophrenia from age 13, and treat qualifying agitation in Alzheimer disease.

The benefits are best understood as modest average improvements, not guarantees. The tradeoffs that matter most are akathisia, weight and metabolic changes, sleepiness, movement effects, drug interactions, and the particular caution required in older adults with dementia.

The most useful question is not “Is Rexulti a good drug?” It is: What exact symptom are we treating, how will we measure whether it helped, which risks matter most for this person, and when will we look at this again?

If you are being prescribed Rexulti, it is entirely fair to ask which of the three jobs you are being treated for. The answer changes what to expect and what to watch.

Frequently asked questions

Is Rexulti an antidepressant?

No. It is an atypical antipsychotic. For adult depression it is approved only as an add-on to an antidepressant, never on its own.[1]

Is Rexulti a mood stabilizer?

“Mood stabilizer” gets used loosely. Rexulti is classified as an antipsychotic and is not FDA approved for bipolar disorder.[1]

Is it approved for bipolar disorder?

No. Two phase 3 trials in acute mania did not beat placebo on the Young Mania Rating Scale at week 3, and bipolar disorder is not on the label.[1,25]

Is it approved for anxiety or PTSD?

No to both. In July 2025 an FDA advisory committee voted 10 to 1 that efficacy had not been established for brexpiprazole started together with sertraline for adult PTSD.[26]

How quickly does it start working?

Blood levels rise within hours, but clinical benefit takes longer. The depression and schizophrenia trials measured their main result at week 6; the Alzheimer agitation trials at week 12. One person’s timeline can differ from all of those.[1]

Does it cause weight gain?

It can. Weight gain appeared in short-term trials and became more common with longer use — about 3.1 kg on average at one year in open-label depression studies, with 30% gaining at least 7% of their starting weight. Weight, blood sugar, and lipids should be monitored.[1]

Can it cause restlessness?

Yes. Akathisia is an uncomfortable inner restlessness that can cause pacing or constant movement, and it occurred in 9% of adults in the depression trials versus 2% on placebo. It can look exactly like anxiety. Report it promptly rather than waiting it out.[1]

Is Rexulti safer than Abilify?

That has not been established. Their receptor profiles and approved uses differ, but the direct comparative evidence needed to call one safer does not exist.[20,21]

Why is it used for Alzheimer agitation if antipsychotics carry a dementia warning?

Because the FDA found evidence of benefit for a specific, serious problem — while the class mortality warning stays in place. It is a genuine benefit-risk decision that should be revisited regularly, not a settled one.[1,3]

Is Rexulti still the only medicine approved for Alzheimer agitation?

No. It was the first, in May 2023. On April 30, 2026, the FDA approved a second option, Auvelity (dextromethorphan and bupropion), which is not an antipsychotic. No trial has compared the two.[3,16,17]

Can it be given only when agitation gets bad?

Not for the approved Alzheimer agitation use. The label states specifically that Rexulti is not an as-needed treatment for that indication.[1]

What if a dose is missed?

Follow the Medication Guide or ask the pharmacist or prescriber. Do not double up. The long half-life does not make self-adjusting safe.[1]

What should be discussed before stopping it?

The reason for stopping, the risk of relapse, side effects, other medicines, the long half-life, and a plan made with the prescriber. This is not a medicine to taper on your own.

Educational disclaimer

This article is for education. It does not diagnose any condition, choose a medication for anyone, or replace the judgment of the clinician who knows your history. Do not start, stop, or change any medication without your prescriber. If there is imminent danger, or you cannot keep yourself or someone else safe, call 911 or go to the nearest emergency department. In the United States, call or text 988, or chat at 988lifeline.org, for any mental-health crisis. For a suspected overdose, call Poison Help at 1-800-222-1222.[28] Every regulatory and numeric claim in this article was verified against primary FDA and journal sources on August 20, 2026. Labels, approvals, and availability change; confirm current status before acting on anything here.

References

1. U.S. Food and Drug Administration. REXULTI (brexpiprazole) tablets — full prescribing information and Medication Guide. NDA 205422, revised 4/2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/205422s017lbl.pdf. Accessed 2026-08-20.
2. DailyMed, U.S. National Library of Medicine. REXULTI (brexpiprazole) tablet — official labeling record. Updated April 23, 2026. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=df891816-3fdb-4347-8bf0-c18bc40f1d70. Accessed 2026-08-20.
3. U.S. Food and Drug Administration. FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia due to Alzheimer’s Disease. Press announcement, May 11, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease. Accessed 2026-08-20.
4. U.S. Food and Drug Administration. Drugs@FDA approval history, NDA 205422 (Rexulti) — original approval July 10, 2015; supplement 7 approved December 27, 2021; supplement 9 approved May 10, 2023; supplement 11 approved May 7, 2024; supplement 14 approved May 9, 2025; supplement 17 approved April 30, 2026. Generic brexpiprazole: 12 abbreviated applications approved, the first on August 11, 2022. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=205422. Accessed 2026-08-20.
5. Lee D, Slomkowski M, Hefting N, et al. Brexpiprazole for the treatment of agitation in Alzheimer dementia: a randomized clinical trial. JAMA Neurol. 2023;80(12):1307-1316. PMID 37930669. doi:10.1001/jamaneurol.2023.3810. ClinicalTrials.gov NCT03548584.
6. U.S. Food and Drug Administration, Office of Surveillance and Epidemiology. Pediatric Postmarketing Pharmacovigilance Review: Rexulti (brexpiprazole) tablets. May 28, 2025. https://www.fda.gov/media/189548/download. Accessed 2026-08-20. Reviewed all serious U.S. FAERS reports in patients under 18 from July 10, 2015 to May 11, 2025; 37 reports identified, no new safety signals and no deaths directly associated with brexpiprazole.
7. Thase ME, Youakim JM, Skuban A, et al. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry. 2015;76(9):1224-1231. PMID 26301701. doi:10.4088/JCP.14m09688. ClinicalTrials.gov NCT01360645.
8. Thase ME, Youakim JM, Skuban A, et al. Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study. J Clin Psychiatry. 2015;76(9):1232-1240. PMID 26301771. doi:10.4088/JCP.14m09689. ClinicalTrials.gov NCT01360632.
9. Ralovska S, Koychev I, Marinov P, Furukawa TA, Mulsant BH, Cipriani A. Brexpiprazole versus placebo or other antidepressive agents for treating depression. Cochrane Database Syst Rev. 2023;7(7):CD013866. doi:10.1002/14651858.CD013866.pub2. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013866.pub2/full
10. Correll CU, Skuban A, Ouyang J, et al. Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia: a 6-week randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2015;172(9):870-880. PMID 25882325. doi:10.1176/appi.ajp.2015.14101275. ClinicalTrials.gov NCT01396421.
11. Kane JM, Skuban A, Ouyang J, et al. A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia. Schizophr Res. 2015;164(1-3):127-135. PMID 25682550. doi:10.1016/j.schres.2015.01.038. ClinicalTrials.gov NCT01393613.
12. Fleischhacker WW, Hobart M, Ouyang J, et al. Efficacy and safety of brexpiprazole (OPC-34712) as maintenance treatment in adults with schizophrenia: a randomized, double-blind, placebo-controlled study. Int J Neuropsychopharmacol. 2017;20(1):11-21. PMID 27566723. doi:10.1093/ijnp/pyw076. ClinicalTrials.gov NCT01668797.
13. Ward C, Pejović Milovančević M, Kohegyi E, et al. Efficacy and safety of brexpiprazole in adolescents with schizophrenia: a multicountry, randomised, double-blind, placebo-controlled, phase 3 trial with an active reference. Lancet Psychiatry. 2025;12(5):345-354. PMID 40209740. doi:10.1016/S2215-0366(25)00043-4. ClinicalTrials.gov NCT03198078.
14. Otsuka Pharmaceutical Development & Commercialization. Protocol 331-14-213: a trial to evaluate the safety, efficacy, and tolerability of brexpiprazole in treating agitation associated with dementia of the Alzheimer’s type. ClinicalTrials.gov NCT03548584, study protocol. Accessed 2026-08-20. Entry required prior evaluation for reversible factors and a prior trial of nonpharmacological interventions; new nonpharmacological interventions were not permitted during the double-blind period.
15. Grossberg GT, Kohegyi E, Mergel V, et al. Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer’s dementia: two 12-week, randomized, double-blind, placebo-controlled trials. Am J Geriatr Psychiatry. 2020;28(4):383-400. PMID 31708380. doi:10.1016/j.jagp.2019.09.009. ClinicalTrials.gov NCT01862640.
16. U.S. Food and Drug Administration. Drugs@FDA approval history, NDA 215430 (Auvelity, dextromethorphan hydrobromide and bupropion hydrochloride) — efficacy supplement 18 approved April 30, 2026 for agitation associated with dementia due to Alzheimer’s disease. Current prescribing information via DailyMed, revised August 2026: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dcefda7c-9a68-278e-e053-2995a90aec79. Accessed 2026-08-20.
17. Alzheimer’s Association. FDA Approves New Treatment for Alzheimer’s Disease Agitation. April 30, 2026. https://www.alz.org/news/2026/alzheimers-association-welcomes-fda-approval-treatment-for-agitation. Accessed 2026-08-20.
18. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-872. PMID 32867516. doi:10.1176/appi.ajp.2020.177901.
19. Massachusetts General Hospital Center for Women’s Mental Health. National Pregnancy Registry for Psychiatric Medications. 1-866-961-2388. https://womensmentalhealth.org/research/pregnancyregistry/. Accessed 2026-08-20.
20. Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014;350(3):589-604. PMID 24947465. doi:10.1124/jpet.114.213793.
21. Kishi T, Ikuta T, Matsuda Y, Sakuma K, Iwata N. Aripiprazole vs. brexpiprazole for acute schizophrenia: a systematic review and network meta-analysis. Psychopharmacology (Berl). 2020;237(5):1459-1470. PMID 32002559. doi:10.1007/s00213-020-05472-5.
22. Kishi T, Sakuma K, Saito T, Nakagawa A, Kato M, Iwata N. Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: a systematic review and network meta-analysis. Neuropsychopharmacol Rep. 2024;44(1):165-175. PMID 38219278. doi:10.1002/npr2.12414.
23. DailyMed, U.S. National Library of Medicine. CAPLYTA (lumateperone) capsule — official labeling record, revised April 2026; adjunctive treatment of major depressive disorder in adults added November 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db730b06-6351-47fd-8183-e61e61bbead5. Accessed 2026-08-20.
24. McIntyre RS, Stahl SM, Shim SR, et al. Adjunctive antipsychotics in major depressive disorder: a systematic review and network meta-analysis. JAMA Psychiatry. 2026;83(7):741-750. PMID 42090141. doi:10.1001/jamapsychiatry.2026.0658.
25. Otsuka Pharmaceutical Co., Ltd., and H. Lundbeck A/S. Otsuka and Lundbeck report phase III data evaluating brexpiprazole for the treatment of manic episodes associated with bipolar I disorder. Company source, February 15, 2019. https://www.otsuka.co.jp/en/company/newsreleases/2019/20190215_1.html. Accessed 2026-08-20. Two trials; neither met the primary endpoint of separation from placebo on the Young Mania Rating Scale at week 3.
26. U.S. Food and Drug Administration. Psychopharmacologic Drugs Advisory Committee meeting, July 18, 2025 — official transcript and FDA presentations. Vote on whether efficacy of brexpiprazole initiated concurrently with sertraline had been established for PTSD: 1 yes, 10 no, 0 abstentions. https://www.fda.gov/media/193310/download and https://www.fda.gov/media/187741/download. Accessed 2026-08-20.
27. DailyMed, U.S. National Library of Medicine. Brexpiprazole tablet (Ajanta Pharma USA Inc.) — generic labeling record. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=993b584c-7fe6-4551-899f-39146c8508ac. Accessed 2026-08-20. Lists two indications and states: “Pediatric use information is approved for Otsuka Pharmaceutical Company, Ltd.’s Rexulti (brexpiprazole) tablets. However, due to Otsuka Pharmaceutical Company, Ltd.’s marketing exclusivity rights, this drug product is not labeled with that information.”
28. Poison Help / Health Resources and Services Administration. Poison emergency guidance. National number 1-800-222-1222. https://www.poisonhelp.org/. Accessed 2026-08-20.

If you or someone you know is in crisis

• Call 911 or go to your nearest emergency room for any life-threatening emergency.
• 988 Suicide & Crisis Lifeline — call or text 988, available 24/7. En español: marque 988 y oprima 2. Veterans: 988 and press 1, or text 838255.
• Crisis Text Line — text HOME to 741741.
• The Trevor Project (crisis support for LGBTQ+ young people) — call 1-866-488-7386, or text START to 678-678.
• National Sexual Assault Hotline (RAINN) — call 1-800-656-HOPE (4673) or text HOPE to 64673; free, confidential, 24/7. Online chat at RAINN.org/hotline.
• National Domestic Violence Hotline — call 1-800-799-SAFE (7233) or text START to 88788; 24/7, help in 200+ languages. Online chat at TheHotline.org. If your phone or computer may be monitored, calling from a safer device is an option.
• Riverside County — Inland SoCal Crisis Helpline 951-686-HELP (4357), 24/7 (Inland SoCal United Way / 211+, in partnership with RUHS-BH); Community Access, Referral, Evaluation and Support (CARES) Line 800-499-3008, 24/7.
• San Bernardino County — Access Unit (Behavioral Health Helpline) 888-743-1478, 24/7; Mobile Crisis/CCRT 800-398-0018 (24/7, all ages) or text 909-420-0560. Arrowhead Regional Medical Center (ARMC) has a dedicated walk-in adolescent psychiatric ER (ages 13–17).
• Children under 13 — call 911 for immediate danger, contact your county's mobile crisis team (they respond to all ages), or go to the nearest pediatric emergency room.
• California Peer-Run Warm Line (non-crisis — someone to talk to) — call or text 1-855-600-WARM (9276); daytime and evening hours, not a 24/7 line.
• NP Fady (non-emergency) — for routine scheduling or questions, call (909) 707-6261. This line is not monitored for emergencies.