What is Rexulti used for and how well does it work?

Key Points

Rexulti (generic name: brexpiprazole) is an oral atypical antipsychotic approved for 3 uses at certain doses: to treat adults and children 13 years and older with schizophrenia, to treat adults as an add-on therapy to antidepressant therapy (ADT) for major depressive disorder (MDD), and to treat agitation associated with dementia due to Alzheimer’s disease.

Follow along to review the clinical trial results for Rexulti in these health conditions, looking at effectiveness, doses and potential side effects.

Overview

In Phase 3 studies at adequate doses, Rexulti led to significantly improved symptoms of these psychiatric disorders when compared to a placebo (a pill with no medicine in it).

• In two 6-week long, double-blind studies in adults, adding Rexulti 2 mg to ongoing antidepressant treatment (SSRI or SNRI) in patients with or without symptoms of anxiety led to a 11.9% greater reduction in symptoms of depression (measured by the Montgomery-Asberg Depression Rating Scale (MADRS) when compared to placebo. Treatment with the 3 mg dose led to a 7.4% reduction that statistically nonsignificant. It is not known if Rexulti is safe and effective in children with MDD.
• In two 6-week studies in adults with schizophrenia, when compared to placebo, the PANSS symptom score (a common scoring tool used in the study of schizophrenia) for Rexulti declined significantly for both the 2 mg and 4 mg per day doses in study 3 and for the 4 mg/day in study 4. In study 4, the 2 mg dose was not found to be statistically significant vs. placebo. An additional trial showed a statistically significant longer time to relapse in patients randomized to Rexulti compared to placebo.
• In two 12-week long, placebo-controlled studies in patients with agitation associated with dementia due to Alzheimer’s disease, those who received Rexulti at 2 mg/day or 3 mg/day doses achieved a statistically significant greater reduction in frequency of agitation symptoms (CMAI total score), compared to the start of the study. The 1 mg dose did not achieve significance.

Rexulti is classified as a serotonin-dopamine activity modulator (SDAM). Rexulti works by adjusting the imbalance of natural chemicals (called neurotransmitters) in the brain to help lower symptoms of these diseases. Neurotransmitters help certain cells to communicate with each other. These chemicals include dopamine and serotonin.

It is an oral tablet you take once a day with or without food. Your doctor will slowly increase your dose over a few weeks based on how well you respond to and tolerate the medicine.

Rexulti is not used as needed (“prn”) in the treatment for agitation associated with dementia due to Alzheimer’s disease.

It comes in strengths of 0.25 milligrams (mg), 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg. The 0.25, 0.5, and 1 mg strengths are only used as starting doses, not for maintenance treatment.

What does Rexulti treat?

An imbalance of neurotransmitters is thought to be linked to several mental health conditions, including depression, schizophrenia, and agitation associated with dementia due to Alzheimer’s disease.

Depression

Depression is a long-term, serious mood disorder that can affect your daily feelings, actions and thoughts. Depression is sometimes called major depressive disorder (MDD).

Depression can cause profound, long-lasting feelings of sadness, tearfulness, loss of interest in daily activities, and often withdrawal from family and friends. In the most severe cases, thoughts of worthlessness, self-harm or suicide may occur.

Schizophrenia

Schizophrenia is also a serious mental health disorder that alters how your brain interprets reality and your surroundings. You may see, hear or believe things that are not real. Your thoughts can be difficult to organize and you may have trouble in social or working environments, affecting your daily functioning.

Agitation associated with dementia due to Alzheimer’s disease

Agitation associated with dementia due to Alzheimer’s disease is a common neuropsychiatric symptom in Alzheimer’s dementia, and can often lead to early nursing home placement. It can be a stressful aspect of the disease for caregivers.

A person with agitation of Alzheimer's dementia may feel irritable, restless, or make repetitive movements. They may walk up and down, or try to leave the house, which can cause safety issues. Other more concerning symptoms may include profanity, shouting, shoving, and hitting.

How well does Rexulti work?

Depression

If you have been taking an antidepressant treatment (ADT) for at least 2 months but are still having symptoms of depression, adding Rexulti to your treatment regimen may be helpful. In a 6-week long study in adults, adding Rexulti to ongoing antidepressant treatment led to a 62% greater reduction in symptoms of depression.

In two depression studies, the effect of treatment was measured using the Montgomery-Asberg Depression Rating Scale (MADRS), a common tool that looks at symptoms of depression such as sad feelings, attention, sleep patterns and appetite. About half of all of patients in the 2 trials also had symptoms of anxiety.

Patients received doses ranging from 1 to 3 mg/day or placebo (an inactive treatment), plus an antidepressant (SSRI or SNRI) treatment (ADT). When compared to score changes with the placebo + ADT, MADRS total scores dropped by:

• -1.3 points (with the 1 mg/day + ADT)
• -2 points (using the 3 mg/day + ADT)
• -3.2 points (using the 2 mg/day + ADT)

Compared to placebo, only the 2 mg/day dose was found to have a statistically significant effect on MADRS score. For most patients with depression, the target dose of Rexulti is 2 mg once daily.

Related questions

• Why does Rexulti cause weight gain?
• How long does it take for Rexulti to work?
• How does Rexulti work?

Schizophrenia

Rexulti has also been shown to be effective for adults with schizophrenia when compared to a placebo in two 6-week long studies. Patients were diagnosed with an acute exacerbation of schizophrenia who could benefit from hospitalization or continued hospitalization.

Researchers determine the effectiveness of Rexulti using the Positive and Negative Syndrome Scale (PANSS) total symptom severity score, a common scoring tool used in the study of schizophrenia.

Overall, at the end of 6 weeks in Study 3, the PANSS symptom score from baseline for patients taking Rexulti had declined significantly for both the 2mg and 4 mg doses. In this study, there was a significant decline in PANSS score of:

• 20.7 points (2 mg/day) with Rexulti compared to a reduction of 12 points with placebo (8.7 point difference).
• 19.7 points (4 mg/day) with Rexulti compared to a reduction of 12 points with placebo (7.6 point difference).

Statistical significance was not achieved for the primary endpoint with the 2-mg/day dose compared with placebo in Study 4 (3.1 point difference) but was significant for the 4 mg/day dose (6.5 point difference).

The recommended target dose for Rexulti is 2 mg or 4 mg once daily in adults and children 13 to 17 years of age with schizophrenia.

Agitation associated with dementia due to Alzheimer’s disease

In two Phase 3, 12-week, placebo-controlled studies, investigators evaluated the frequency of agitation symptoms in patients with dementia due to Alzheimer’s disease based on the Cohen-Mansfield Agitation Inventory (CMAI) total score.

• The primary endpoint was a change in agitation symptom frequency (CMAI total score) from baseline at Week 12 in both studies. The CMAI is a clinician rated questionnaire consisting of 29 items, which assesses the frequency of agitated behaviors in elderly patients, based on caregiver input.
• Patients in Study 6 receiving the Rexulti 2 mg/day dose (-3.8 point difference from placebo), or the 2mg or 3 mg/day dose (-3.8 point difference from placebo) in Study 7 achieved a small, but significantly greater reduction from baseline in frequency of agitation symptoms vs. placebo.
• The 1 mg/day dose did not demonstrate significantly greater mean changes at baseline from the placebo group and this dose is not approved as a maintenance dose.

Warnings / Side Effects

• Antipsychotic medicines like Rexulti can raise the risk of death in elderly patients who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Rexulti is not approved to treat patients with dementia-related psychosis without agitation associated with dementia due to Alzheimer’s disease.
• Other important warnings include an increased risk of suicidal thoughts and actions in pediatric and young adult patients.
• Rexulti carries a Boxed Warning for these possible risks.

Other warnings include the risk of stroke or other cerebrovascular side effects, neuroleptic malignant syndrome, uncontrolled body movements, weight gain, high blood sugar, diabetes, compulsive urges, falls, seizures, decreased blood pressure, risk of fainting, low white blood cell count, trouble swallowing and an increase in blood fats, like cholesterol or triglycerides.

The most common side effects of Rexulti include:

• Weight gain
• Sleepiness
• Dizziness
• Common cold symptoms
• Restlessness or feeling like you need to move (known as akathisia)

There are many other important warnings, side effects and drug interactions associated with Rexulti treatment. Speak with your doctor about the safety of Rexulti before you begin treatment. Be sure to tell your doctor and pharmacist about all of the medicines you take, including prescription, over-the-counter, herbal products and vitamin supplements.

Bottom Line

• Rexulti (brexpiprazole), an atypical antipsychotic, is used with an antidepressant medicine to treat adult patients diagnosed with major depressive disorder (depression); in adults and children 13 years and older with schizophrenia; and to treat agitation associated with dementia due to Alzheimer’s disease
• In placebo-controlled studies, appropriate doses of Rexulti was shown to have a significant effect on symptom severity (when compared to placebo) in patients with these conditions.
• Rexulti is thought to work by adjusting the balance of natural chemicals (neurotransmitters) in the brain (such as dopamine and serotonin). An imbalance of neurotransmitters is thought to be linked to several mental health conditions.

This is not all the information you need to know about Rexulti (brexpiprazole) for safe and effective use. Review the full Rexulti information here, and discuss this information and any questions with your doctor or other health care provider.