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Rexulti (brexpiprazole) - 3 indications
Scroll down for additional information for each indication:
- for the treatment of depression and schizophrenia in adults; approved July 2015
- for the treatment of agitation associated with dementia due to Alzheimer’s disease; approved May of 2023
General Information
Rexulti (brexpiprazole) is an atypical antipsychotic.
Rexulti is specifically indicated:
- for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults
- for the treatment of schizophrenia in adults and pediatric patients ages 13 years and older
- for the treatment of agitation associated with dementia due to Alzheimer’s disease
Rexulti is supplied as a tablet for oral administration. Scroll down for specific dosing and administration recommendations for each indication:
Mechanism of Action
Rexulti (brexpiprazole) is an atypical antipsychotic. The mechanism of action of brexpiprazole in the treatment of major depressive disorder or schizophrenia is unknown. However, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.
Side Effects
Adverse effects associated with the use of Rexulti may include, but are not limited to, the following:
- akathisia
- weight gain
Rexulti comes with a black box warning of increased mortality in elderly patients with dementia-related psychosis; and a potential risk in the increase of the risk of suicidal thoughts and behaviors in patients aged 24 years and younger.
Indication 1 - as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults
The efficacy of Rexulti in the adjunctive treatment of major depressive disorder (MDD) was evaluated in two 6-week, double-blind, placebo-controlled, fixed-dose trials of adults meeting DSM-IV-TR criteria for MDD, with or without symptoms of anxiety, who had an inadequate response to prior antidepressant therapy (1 to 3 courses) in the current episode and who had also demonstrated an inadequate response throughout the 8 weeks of prospective antidepressant treatment. In Study 228 (Study 1) subjects were randomized to Rexulti 2 mg once a day or placebo. In Study 227 (Study 2) subjects were randomized to Rexulti 1 or 3 mg once a day or placebo. For subjects randomized to Rexulti, all subjects initiated treatment at 0.5 mg once daily during Week 1. At Week 2, the Rexulti dosage was increased to 1 mg in all treatment groups, and either maintained at 1 mg or increased to 2 mg or 3 mg once daily, based on treatment assignment, from Week 3 onwards. The dosages were then maintained for the 4 remaining weeks. The primary endpoint was change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-related scale used to assess the degree of depressive symptomatology, with 0 representing no symptoms, and 60 representing worst symptoms. At randomization, the mean MADRS total score was 27. In both studies adjunctive brexpiprazole showed greater improvement than adjunctive placebo in MADRS total score at Week 6 in the efficacy population per final protocol in Study 1 (2mg+ADT [N=175]: -3.21), and in Study 2 (1mg+ADT [N=211]: -1.30, 3mg+ADT [N=213]: -1.95). Similar results were observed for the efficacy population in both studies. The completion rate was high (>90%) and comparable across brexpiprazole and placebo groups.
Indication 2 - for the treatment of schizophrenia in adults and pediatric patients ages 13 years and older
Clinical Trial Results
The efficacy of Rexulti in the treatment of adults with schizophrenia was demonstrated in two 6-week, randomized, double-blind, placebo-controlled, fixed-dose clinical trials in subjects who met DSM-IV-TR criteria for schizophrenia. In both studies, Study 231 (Study 3) and Study 230 (Study 4), subjects were randomized to Rexulti 2 or 4 mg once per day or placebo. Subjects in the Rexulti groups initiated treatment at 1 mg once daily on Days 1 to 4. The Rexulti dosage was increased to 2 mg on Days 5 to 7. The dosage was then either maintained at 2 mg once daily or increased to 4 mg once daily, depending on treatment assignment, for the 5 remaining weeks. The primary efficacy endpoint of both trials was the change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score. In one study, brexpiprazole 4mg and 2mg demonstrated greater improvement than placebo in the primary endpoint of change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (4mg: -19.65 and 2mg: -20.73 vs. placebo -12.01; 0.25mg was similar to placebo -14.90). In the other study, brexpiprazole 4mg showed improvement over placebo in the primary endpoint of PANSS Total Score from baseline to Week 6 (-20.0 vs. -13.5), while the 2mg (-16.6) and 1mg (-16.9) doses showed numeric improvement versus placebo (-13.5).
The efficacy of Rexulti in the treatment of adults with schizophrenia was demonstrated in two 6-week, randomized, double-blind, placebo-controlled, fixed-dose clinical trials in subjects who met DSM-IV-TR criteria for schizophrenia. In both studies, Study 231 (Study 3) and Study 230 (Study 4), subjects were randomized to Rexulti 2 or 4 mg once per day or placebo. Subjects in the Rexulti groups initiated treatment at 1 mg once daily on Days 1 to 4. The Rexulti dosage was increased to 2 mg on Days 5 to 7. The dosage was then either maintained at 2 mg once daily or increased to 4 mg once daily, depending on treatment assignment, for the 5 remaining weeks. The primary efficacy endpoint of both trials was the change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score. In one study, brexpiprazole 4mg and 2mg demonstrated greater improvement than placebo in the primary endpoint of change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score (4mg: -19.65 and 2mg: -20.73 vs. placebo -12.01; 0.25mg was similar to placebo -14.90). In the other study, brexpiprazole 4mg showed improvement over placebo in the primary endpoint of PANSS Total Score from baseline to Week 6 (-20.0 vs. -13.5), while the 2mg (-16.6) and 1mg (-16.9) doses showed numeric improvement versus placebo (-13.5).
Indication 3 - for the treatment of agitation associated with dementia due to Alzheimer’s disease
Approval Date: 2015-07-01
Company Name: Otsuka
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